@article {pmid35776638, year = {2022}, author = {Li, X and Wu, P and Zeng, X and Lang, Q and Lin, Y and Huang, H and Qian, P}, title = {Protocol for correlation analysis of the murine gut microbiome and meta-metabolome using 16S rDNA sequencing and UPLC-MS.}, journal = {STAR protocols}, volume = {3}, number = {3}, pages = {101494}, doi = {10.1016/j.xpro.2022.101494}, pmid = {35776638}, issn = {2666-1667}, abstract = {The gut microbiota and metabolites play pivotal roles in the pathobiology of various diseases. Here, we describe a protocol to profile the gut microbiome and meta-metabolome of a mouse disease model for acute graft-versus-host disease. We describe steps for fecal sample collection and processing for 16S sequencing and UPLC-MS. Finally, we detail the steps for data analysis and exhibit multi-omic associations to correlate with pathology. For complete details on the use and execution of this protocol, please refer to Li et al. (2020).}, }
@article {pmid35776086, year = {2022}, author = {Yang, J and Yang, H and Li, Y}, title = {The triple interactions between gut microbiota, mycobiota and host immunity.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-21}, doi = {10.1080/10408398.2022.2094888}, pmid = {35776086}, issn = {1549-7852}, abstract = {The gut microbiome is mainly composed of microbiota and mycobiota, both of which play important roles in the development of the host immune system, metabolic regulation, and maintenance of intestinal homeostasis. With the increasing awareness of the pathogenic essence of infectious, immunodeficiency, and tumor-related diseases, the interactions between gut bacteria, fungi, and host immunity have been shown to directly influence the disease process or final therapeutic outcome, and collaborative and antagonistic relationships are commonly found between bacteria and fungi. Interventions represented by probiotics, prebiotics, engineered probiotics, fecal microbiota transplantation (FMT), and drugs can effectively modulate the triple interactions. In particular, traditional probiotics represented by Bifidobacterium and Lactobacillus and next-generation probiotics represented by Akkermansia muciniphila and Faecalibacterium prausnitzii showed a high enrichment trend in the gut of patients with a high response to inflammation remission and tumor immunotherapy, which predicts the potential medicinal value of these beneficial microbial formulations. However, there are bottlenecks in all these interventions that need to be broken. Meanwhile, further unraveling the underlying mechanisms of the "triple interactions" model can guide precise interventions and ultimately improve the efficiency of interventions on the host gut microbiome and immune modulation, thus directly or indirectly improving anti-inflammatory and tumor immunotherapy effects.}, }
@article {pmid35774395, year = {2022}, author = {Lee, SH and Park, HK and Kang, CD and Choi, DH and Park, SC and Park, JM and Nam, SJ and Chae, GB and Lee, KY and Cho, H and Lee, SJ}, title = {High Dose Intramuscular Vitamin D3 Supplementation Impacts the Gut Microbiota of Patients With Clostridioides Difficile Infection.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {904987}, doi = {10.3389/fcimb.2022.904987}, pmid = {35774395}, issn = {2235-2988}, abstract = {Background and Aim: Current therapeutic strategies for Clostridioides difficile infections (CDI), including oral vancomycin, metronidazole and fecal microbial transplantation, have limited efficacy and treatment failure may occur in as many as one- third of cases. Recent studies have reported that lower concentrations of 25-hydroxyvitamin D are associated with CDI severity and recurrence. However, there have been no studies on microbiota composition after the administration of vitamin D in patients with CDI. Therefore, our study aimed to compare the microbiota composition between the two groups, including eight CDI-positive patients with vitamin D supplementation and ten CDI-positive patients without vitamin D supplementation by using 16S rRNA microbial profiling.
Methods: Twenty subjects were enrolled in this prospective randomized controlled study. One subject dropped out due to lack of contact with the guardian after discharge and one subject dropped out due to withdrawal of consent. Thus, 18 patients with CDI and vitamin D insufficiency (vitamin D level < 17 ng/mL) were divided into two groups: CDI with vitamin D supplementation (n = 8) and CDI without vitamin D supplementation (control: n = 10). Subjects with vitamin D insufficiency were randomized to receive 200,000 IU intramuscular cholecalciferol whereas patients in the control group received only oral vancomycin. Stool samples were obtained twice before vancomycin was administered and eight weeks after treatment; the V3-V4 16S rRNA metagenomic sequencing was performed using EzBioCloud.
Results: The alpha diversity of the gut microbiota in the recovery state was significantly higher than that in the CDI state. Analysis of bacterial relative abundance showed significantly lower Proteobacteria and higher Lachnospiraceae, Ruminococcaceae, Akkermansiaceae, and Bifidobacteriaceae in the recovery state. When comparing the control and vitamin D treatment groups after eight weeks, increase in alpha diversity and, abundance of Lachnospiraceae, and Ruminococcaceae exhibited the same trend in both groups. A significant increase in Bifidobacteriaceae and Christensenellaceae was observed in the vitamin D group; Proteobacteria abundance was significantly lower in the vitamin D treatment group after eight weeks than that in the control group.
Conclusion: Our study confirmed that the increase in the abundance of beneficial bacteria such as Bifidobacteriaceae, and Christensenellaceae were prominently evident during recovery after administration of a high dose of cholecalciferol. These findings indicate that vitamin D administration may be useful in patients with CDI, and further studies with larger sample sizes are required.}, }
@article {pmid35766805, year = {2022}, author = {El Hage Chehade, N and Ghoneim, S and Shah, S and Chahine, A and Mourad, FH and Francis, FF and Binion, DG and Farraye, FA and Hashash, JG}, title = {Efficacy of Fecal Microbiota Transplantation in the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izac135}, pmid = {35766805}, issn = {1536-4844}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been investigated as a treatment option for patients with inflammatory bowel disease with controversial results.We sought to perform a systematic review and meta-analysis to evaluate the benefit of FMT in patients with ulcerative colitis.
METHODS: Double-blind randomized controlled trials (RCTs) including adult patients with active ulcerative colitis who received either FMT or placebo were eligible for inclusion. Outcomes of interest included the rate of combined clinical and endoscopic remission, endoscopic remission or response, clinical remission or response, and specific adverse events. The results were pooled together using Reviewer Manager 5.4 software. Publication bias was assessed using the Egger's test.
RESULTS: Six RCTs involving 324 patients were included. Our findings demonstrate that compared with placebo, FMT has significant benefit in inducing combined clinical and endoscopic remission (odds ratio, 4.11; 95% confidence interval, 2.19-7.72; P < .0001). Subgroup analyses of influencing factors showed no differences between pooled or single stool donors (P = .71), fresh or frozen FMT (P = .35), and different routes or frequencies of delivery (P = .80 and .48, respectively). Pre-FMT antibiotics, bowel lavage, concomitant biologic therapy, and topical rectal therapy did not affect combined remission rates (P values of .47, .38, .28, and .40, respectively). Clinical remission or response and endoscopic remission or response were significantly higher in patients who received FMT compared with placebo (P < .05) without any differences in serious or specific adverse events.
CONCLUSIONS: FMT demonstrated a clinical and endoscopic benefit in the short-term treatment of active ulcerative colitis, with a comparable safety profile to placebo. Future RCTs are required to standardize study protocols and examine data on maintenance therapy.}, }
@article {pmid35766265, year = {2022}, author = {Wang, H and Yao, J and Chen, Y and Wang, Y and Liu, Y and Liao, Y and Liang, Z and Dong, YH and Qu, M and Ge, X and Zhou, X}, title = {Gut dysbacteriosis attenuates resistance to Mycobacterium bovis infection by decreasing Cyclooxygenase 2 to inhibit endoplasmic reticulum stress.}, journal = {Emerging microbes & infections}, volume = {}, number = {}, pages = {1-31}, doi = {10.1080/22221751.2022.2096486}, pmid = {35766265}, issn = {2222-1751}, abstract = {AbstractThe role of gut microbiota has been described as an important influencer of the immune system. Gut-lung axis is critical in the prevention of mycobacterium infection, but the specific mechanism by which dysbiosis affects tuberculosis have not been reported. In this study, we attempted to provide more information on how the gut-lung axis contributes to Mycobacterium bovis (M. bovis) infection. Mice pre-treated with broad-spectrum antibiotics cocktail (Abx) to induce gut dysbiosis. Interestingly, dysbiosis of microbes showed a significant increase in the bacterial burden in lungs, and inhibited the level of COX-2. After fecal transplantation, cyclooxygenase 2（COX-2） expression was restored and the inflammatory lesion in the lung was reduced. Further research found that the deficiency of COX-2 inhibited endoplasmic reticulum stress (ER-stress). This mechanism was completed by COX-2 interaction with BIP. Moreover, we found a positive feedback mechanism by which blocking ER-stress could reduce COX-2 levels via the NF-κB pathway. Taken together, we reveal for the first time gut dysbacteriosis exacerbates M. bovis disease by limiting COX-2 /ER-stress pathway. The finding strengthens the foundation of gut microbiota-targeted therapy for tuberculosis treatment.}, }
@article {pmid35765243, year = {2022}, author = {Hu, LP and Huang, W and Wang, X and Xu, C and Qin, WT and Li, D and Tian, G and Li, Q and Zhou, Y and Chen, S and Nie, HZ and Hao, Y and Song, J and Zhang, XL and Sundquist, J and Sundquist, K and Li, J and Jiang, SH and Zhang, ZG and Ji, J}, title = {Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2022.06.015}, pmid = {35765243}, issn = {1525-0024}, abstract = {Existing evidence indicates that gut fungal dysbiosis might play a key role in the pathogenesis of colorectal cancer (CRC). We sought to explore whether reversing the fungal dysbiosis by terbinafine, an approved antifungal drug, might inhibit the development of CRC. A population-based study from Sweden identified a total of 185 patients who received terbinafine after their CRC diagnosis and found that they had a decreased risk of death (hazard ratio=0.50) and metastasis (hazard ratio=0.44) compared with patients without terbinafine administration. In multiple mouse models of CRC, administration of terbinafine decreased the fungal load, the fungus-induced myeloid-derived suppressor cell (MDSC) expansion, and the tumor burden. Fecal microbiota transplantation from mice without terbinafine treatment reversed MDSC infiltration and partially restored tumor proliferation. Mechanistically, terbinafine directly impaired tumor cell proliferation by reducing the ratio of nicotinamide adenine dinucleotide phosphate (NADP+) to reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), suppressing the activity of glucose-6-phosphate dehydrogenase (G6PD), resulting in nucleotide synthesis disruption, deoxyribonucleotide (dNTP) starvation and cell cycle arrest. Collectively, terbinafine can inhibit CRC by reversing fungal dysbiosis, suppressing tumor cell proliferation, inhibiting fungus-induced MDSC infiltration, and restoring antitumor immune response.}, }
@article {pmid35764988, year = {2022}, author = {Ma, P and Mo, R and Liao, H and Qiu, C and Wu, G and Yang, C and Zhang, Y and Zhao, Y and Song, XJ}, title = {Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice.}, journal = {Journal of neuroinflammation}, volume = {19}, number = {1}, pages = {169}, pmid = {35764988}, issn = {1742-2094}, support = {KQTD20200820113040070//Science, Technology and Innovation Commission of Shenzhen Municipality/ ; JCYJ20200109141433384//The Foundation of Shenzhen Science and Technology Innovation Committee/ ; 7191001//Natural Science Foundation of Beijing Municipality/ ; NFSC81971062//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Gut microbiota has been found involved in neuronal functions and neurological disorders. Whether and how gut microbiota impacts chronic somatic pain disorders remain elusive.
METHODS: Neuropathic pain was produced by different forms of injury or diseases, the chronic constriction injury (CCI) of the sciatic nerves, oxaliplatin (OXA) chemotherapy, and streptozocin (STZ)-induced diabetes in mice. Continuous feeding of antibiotics (ABX) cocktail was used to cause major depletion of the gut microbiota. Fecal microbiota, biochemical changes in the spinal cord and dorsal root ganglion (DRG), and the behaviorally expressed painful syndromes were assessed.
RESULTS: Under condition of gut microbiota depletion, CCI, OXA, or STZ treatment-induced thermal hyperalgesia or mechanical allodynia were prevented or completely suppressed. Gut microbiota depletion also prevented CCI or STZ treatment-induced glial cell activation in the spinal cord and inhibited cytokine production in DRG in OXA model. Interestingly, STZ treatment failed to induce the diabetic high blood glucose and painful hypersensitivity in animals with the gut microbiota depletion. ABX feeding starting simultaneously with CCI, OXA, or STZ treatment resulted in instant analgesia in all the animals. ABX feeding starting after establishment of the neuropathic pain in CCI- and STZ-, but not OXA-treated animals produced significant alleviation of the thermal hyeralgesia or mechanical allodynia. Transplantation of fecal bacteria from SPF mice to ABX-treated mice partially restored the gut microbiota and fully rescued the behaviorally expressed neuropathic pain, of which, Akkermansia, Bacteroides, and Desulfovibrionaceae phylus may play a key role.
CONCLUSION: This study demonstrates distinct roles of gut microbiota in the pathogenesis of chronic painful conditions with nerve injury, chemotherapy and diabetic neuropathy and supports the clinical significance of fecal bacteria transplantation.}, }
@article {pmid35760542, year = {2022}, author = {Hurych, J and Vejmelka, J and Hlinakova, L and Kramna, L and Larionov, V and Kulich, M and Cinek, O and Kohout, P}, title = {Protocol for faecal microbiota transplantation in irritable bowel syndrome: the MISCEAT study - a randomised, double-blind cross-over study using mixed microbiota from healthy donors.}, journal = {BMJ open}, volume = {12}, number = {6}, pages = {e056594}, doi = {10.1136/bmjopen-2021-056594}, pmid = {35760542}, issn = {2044-6055}, mesh = {Cross-Over Studies ; Diarrhea/therapy ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/methods ; Humans ; *Irritable Bowel Syndrome/therapy ; *Microbiota ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Several studies have demonstrated dysbiosis in irritable bowel syndrome (IBS). Therefore, faecal microbiota transplantation, whose effect and safety have been proven in Clostridioides difficile infections, may hold promise in other conditions, including IBS. Our study will examine the effectiveness of stool transfer with artificially increased microbial diversity in IBS treatment.
METHODS AND ANALYSIS: A three-group, double-blind,randomised, cross-over, placebo-controlled study of two pairs of gut microbiota transfer will be conducted in 99 patients with diarrhoeal or mixed type of IBS. Patients aged 18-65 will be randomised into three equally sized groups: group A will first receive two enemas of study microbiota mixture (deep-frozen stored stool microbiota mixed from eight healthy donors); after 8 weeks, they will receive two enemas with placebo (autoclaved microbiota mixture), whereas group B will first receive placebo, then microbiota mixture. Finally, group C will receive placebos only. The IBS Severity Symptom Score (IBS-SSS) questionnaires will be collected at baseline and then at weeks 3, 5, 8, 11, 13, 32. Faecal bacteriome will be profiled before and regularly after interventions using 16S rDNA next-generation sequencing. Food records, dietary questionnaires, anthropometry, bioimpedance, biochemistry and haematology workup will be obtained at study visits during the follow-up period. The primary outcome is the change in the IBS-SSS between the baseline and 4 weeks after the intervention for each patient compared with placebo. Secondary outcomes are IBS-SSS at 2 weeks after the intervention and 32 weeks compared with placebo and changes in the number of loose stools, Bristol stool scale, abdominal pain and bloating, anthropometric parameters, psychological evaluation and the gut microbiome composition.
ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Thomayer University Hospital, Czechia (G-18-26); study results will be published in peer-reviewed journals and presented at international conferences and patient group meetings.
TRIAL REGISTRATION NUMBER: NCT04899869.}, }
@article {pmid35759305, year = {2022}, author = {Davis, BT and Chen, Z and Islam, MBAR and Timken, ME and Procissi, D and Schwulst, SJ}, title = {Fecal Microbiota Transfer Attenuates Gut Dysbiosis and Functional Deficits After Traumatic Brain Injury.}, journal = {Shock (Augusta, Ga.)}, volume = {57}, number = {6}, pages = {251-259}, doi = {10.1097/SHK.0000000000001934}, pmid = {35759305}, issn = {1540-0514}, mesh = {Animals ; *Brain Injuries, Traumatic/pathology ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Humans ; Mice ; *Neurodegenerative Diseases ; }, abstract = {BACKGROUND: Traumatic brain injury (TBI) is an underrecognized public health threat. Survivors of TBI often suffer long-term neurocognitive deficits leading to the progressive onset of neurodegenerative disease. Recent data suggests that the gut-brain axis is complicit in this process. However, no study has specifically addressed whether fecal microbiota transfer (FMT) attenuates neurologic deficits after TBI.
HYPOTHESIS: We hypothesized that fecal microbiota transfer would attenuate neurocognitive, anatomic, and pathologic deficits after TBI.
METHODS: C57Bl/6 mice were subjected to severe TBI (n = 20) or sham-injury (n = 20) via an open-head controlled cortical impact. Post-injury, this cohort of mice underwent weekly oral gavage with a slurry of healthy mouse stool or vehicle alone beginning 1 h post-TBI followed by behavioral testing and neuropathologic analysis. 16S ribosomal RNA sequencing of fecal samples was performed to characterize gut microbial community structure pre- and post-injury. Zero maze and open field testing were used to evaluate post-traumatic anxiety, exploratory behavior, and generalized activity. 3D, contrast enhanced, magnetic resonance imaging was used to determine differences in cortical volume loss and white matter connectivity. Prior to euthanasia, brains were harvested for neuropathologic analysis.
RESULTS: Fecal microbiome analysis revealed a large variance between TBI, and sham animals treated with vehicle, while FMT treated TBI mice had restoration of gut dysbiosis back to levels of control mice. Neurocognitive testing demonstrated a rescue of normal anxiety-like and exploratory behavior in TBI mice treated with FMT. FMT treated TBI mice spent a greater percentage of time (22%, P = 0.0001) in the center regions of the Open Field as compared to vehicle treated TBI mice (13%). Vehicle-treated TBI animals also spent less time (19%) in the open areas of zero maze than FMT treated TBI mice (30%, P = 0.0001). Comparing in TBI mice treated with FMT, MRI demonstrated a marked attenuation in ventriculomegaly (P < 0.002) and a significant change in fractional anisotropy (i.e., loss of white matter connectivity) (P < 0.0001). Histologic analysis of brain sections revealed a FMT- injury dependent interaction in the microglia/macrophage-specific ionized calcium-binding protein, Iba1 (P = 0.002).
CONCLUSION: These data suggest that restoring a pre-injury gut microbial community structure may be a promising therapeutic intervention after TBI.}, }
@article {pmid35731859, year = {2022}, author = {Borody, TJ and Dolai, S and Gunaratne, AW and Clancy, RL}, title = {Targeting the microbiome in Crohn's disease.}, journal = {Expert review of clinical immunology}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/1744666X.2022.2093186}, pmid = {35731859}, issn = {1744-8409}, }
@article {pmid35763604, year = {2022}, author = {Rakotonirina, A and Galperine, T and Allémann, E}, title = {Fecal microbiota transplantation: a review on current formulations in Clostridioides difficile infection and future outlooks.}, journal = {Expert opinion on biological therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14712598.2022.2095901}, pmid = {35763604}, issn = {1744-7682}, abstract = {INTRODUCTION: The role of the gut microbiota in health and the pathogenesis of several diseases has been highlighted in recent years. Even though the precise mechanisms involving the microbiome in these ailments are still unclear, microbiota-modulating therapies have been developed. Fecal microbiota transplantation (FMT) has shown significant results against Clostridioides difficile infection (CDI), and its potential has been investigated for other diseases. Unfortunately, the technical aspects of the treatment make it difficult to implement. Pharmaceutical technology approaches to encapsulate microorganisms could play an important role in providing this treatment and render the treatment modalities easier to handle.
AREAS COVERED: After an overview of CDI, this narrative review aims to discuss the current formulations for FMT and specifically addresses the technical aspects of the treatment. This review also distinguishes itself by focusing on the hurdles and emphasizing the possible improvements using pharmaceutical technologies.
EXPERT OPINION: FMT is an efficient treatment for recurrent CDI. However, its standardization is overlooked. The approach of industrial and hospital preparations of FMT are different, but both show promise in their respective methodologies. Novel FMT formulations could enable further research on dysbiotic diseases in the future.}, }
@article {pmid35762770, year = {2022}, author = {Ma, L and Shen, Q and Lyu, W and Lv, L and Wang, W and Yu, M and Yang, H and Tao, S and Xiao, Y}, title = {Clostridium butyricum and Its Derived Extracellular Vesicles Modulate Gut Homeostasis and Ameliorate Acute Experimental Colitis.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0136822}, doi = {10.1128/spectrum.01368-22}, pmid = {35762770}, issn = {2165-0497}, abstract = {Microbiological treatments are expected to have a role in the future management of inflammatory bowel disease (IBD). Clostridium butyricum (C. butyricum) is a probiotic microorganism that exhibits beneficial effects on various disease conditions. Although many studies have revealed that C. butyricum provides protective effects in mice with colitis, the way C. butyricum establishes beneficial results in the host remains unclear. In this study, we investigated the mechanisms by which C. butyricum modifies the gut microbiota, produces bacterial metabolites that may be involved, and, specifically, how microbial extracellular vesicles (EVs) positively influence IBD, using a dextran sulfate sodium (DSS)-induced colitis murine model in mice. First, we showed that C. butyricum provides a protective effect against colitis, as evidenced by the prevention of body weight loss, a reduction in the disease activity index (DAI) score, a shortened colon length, decreased histology score, and an improved gut barrier function, accompanied by reduced levels of pathogenic bacteria, including Escherichia/Shigella, and an increased relative abundance of butyrate-producing Clostridium sensu stricto-1 and Butyricicoccus. Second, we also confirmed that the gut microbiota and metabolites produced by C. butyricum played key roles in the attenuation of DSS-induced experimental colitis, as supported by the profound alleviation of colitis effects following fecal transplantation or fecal filtrate insertion supplied from C. butyricum-treated mice. Finally, C. butyricum-derived EVs protected the gut barrier function, improved gut microbiota homeostasis in ulcerative colitis, and contributed to overall colitis alleviation. IMPORTANCE This study indicated that C. butyricum provided a prevention effect against colitis mice, which involved protection of the intestinal barrier and positively regulating gut microbiota. Furthermore, we confirmed that the gut microbiota and metabolites that were induced by C. butyricum also contributed to the attenuation of DSS-induced colitis. Importantly, C. butyricum-derived EVs showed an effective impact in alleviating colitis.}, }
@article {pmid35611465, year = {2022}, author = {Gulliver, EL and Young, RB and Chonwerawong, M and D'Adamo, GL and Thomason, T and Widdop, JT and Rutten, EL and Rossetto Marcelino, V and Bryant, RV and Costello, SP and O'Brien, CL and Hold, GL and Giles, EM and Forster, SC}, title = {Review article: the future of microbiome-based therapeutics.}, journal = {Alimentary pharmacology & therapeutics}, volume = {56}, number = {2}, pages = {192-208}, doi = {10.1111/apt.17049}, pmid = {35611465}, issn = {1365-2036}, support = {DP190101504//Australian Research Council/ ; //Victorian Government/ ; }, mesh = {Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {BACKGROUND: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic.
AIM: This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development.
METHODS: Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical interventions. Key literature was identified through Pubmed searches with the following key words, 'microbiome', 'microbiome biomarkers', 'probiotics', 'prebiotics', 'synbiotics', 'faecal microbiota transplant', 'live biotherapeutics', 'microbiome mimetics' and 'postbiotics'.
RESULTS: Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, rationally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics.
CONCLUSIONS: Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation.}, }
@article {pmid35759806, year = {2022}, author = {Li, Z and Ke, H and Lin, Q and Shen, Z and Chen, Y}, title = {Global trends in gut microbiota and clostridioides difficile infection research: A visualized study.}, journal = {Journal of infection and public health}, volume = {15}, number = {7}, pages = {806-815}, doi = {10.1016/j.jiph.2022.06.011}, pmid = {35759806}, issn = {1876-035X}, abstract = {BACKGROUND: Clostridioides (clostridium) difficile infection (CDI) is the most common cause of nosocomial diarrheal disease, which has become a public health problem worldwide; gut dysbiosis plays a central role in its pathophysiology. This study conducted a bibliometric analysis of publications on gut microbiota and CDI to summarize the current status of research including research hotspots.
METHODS: Relevant publications from January 2004 to February 2022 were identified from the Web of Science Core Collection. Three bibliometric tools were used to perform visualization analyses.
RESULTS: A total of 1983 publications were analyzed. Annual publications increased from 11 in 2004-237 in 2021, with the US being the leading producer (47.55 % of all papers). EG Pamer had the highest average citations per article (average citations per item = 153.03, H-index = 29). Frontiers in Microbiology published the most papers. The main research foci were "fecal microbiota transplantation," "colonization resistance," and "multidrug-resistant bacteria." The keywords with the highest frequency in recent years include: gut dysbiosis, antibiotic resistance, bile-acids, 16 s sequencing, multidrug-resistant bacteria, and short chain fatty acids.
CONCLUSIONS: Gut microbiota and CDI is likely to remain a prominent area of research in the foreseeable future. Current research hotspots ("fecal microbiota transplantation," "colonization resistance," and "multidrug-resistant bacteria") should receive even more attention in future studies.}, }
@article {pmid35759388, year = {2022}, author = {Jiang, L and Hong, Y and Xiao, P and Wang, X and Zhang, J and Liu, E and Li, H and Cai, Z}, title = {The Role of Fecal Microbiota in Liver Toxicity Induced by Perfluorooctane Sulfonate in Male and Female Mice.}, journal = {Environmental health perspectives}, volume = {130}, number = {6}, pages = {67009}, doi = {10.1289/EHP10281}, pmid = {35759388}, issn = {1552-9924}, abstract = {BACKGROUND: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that can cause hepatotoxicity. The underlying toxicological mechanism remains to be investigated. Given the critical role of fecal microbiota in liver function, it is possible that fecal microbiota may contribute to the liver toxicity induced by PFOS.
OBJECTIVES: We aimed to investigate the role of liver-fecal microbiota axis in modulating PFOS-induced liver injury in mice.
METHODS: Male and female mice were exposed to PFOS or vehicle for 14 d. In this investigation, 16S rDNA sequencing and metabolomic profiling were performed to identify the perturbed fecal microbiota and altered metabolites with PFOS exposure. In addition, antibiotic treatment, fecal microbiota transplantation, and bacterial administration were conducted to validate the causal role of fecal microbiota in mediating PFOS-induced liver injury and explore the potential underlying mechanisms.
RESULTS: Both male and female mice exposed to PFOS exhibited liver inflammation and steatosis, which were accompanied by fecal microbiota dysbiosis and the disturbance of amino acid metabolism in comparison with control groups. The hepatic lesions were fecal microbiota-dependent, as supported by antibiotic treatment and fecal microbiota transplantation. Mice with altered fecal microbiota in antibiotic treatment or fecal microbiota transplantation experiments exhibited altered arginine concentrations in the liver and feces. Notably, we observed sex-specific lower levels of key microbiota, including Lactobacillus, Enterococcus, and Akkermansia. Mice treated with specific bacteria showed lower arginine levels and lower expression of the phosphorylated mTOR and P70S6K, suggesting lower activity of the related pathway and mitigation of the pathological differences observed in PFOS-exposed mice.
CONCLUSIONS: Our study demonstrated the critical role of the fecal microbiota in PFOS-induced liver injury in mice. We also identified several critical bacteria that could protect against liver injury induced by PFOS in male and female mice. Our present research provided novel insights into the mechanism of PFOS-induced liver injury in mice. https://doi.org/10.1289/EHP10281.}, }
@article {pmid35757563, year = {2020}, author = {Soto Chervin, C and Gajewski, TF}, title = {Microbiome-based interventions: therapeutic strategies in cancer immunotherapy.}, journal = {Immuno-oncology technology}, volume = {8}, number = {}, pages = {12-20}, doi = {10.1016/j.iotech.2020.11.001}, pmid = {35757563}, issn = {2590-0188}, abstract = {The composition of the commensal microbiota has recently emerged as a key element influencing the efficacy of cancer treatments. It has become apparent that the interplay between the microbiome and immune system within the host influences the response to immunotherapy, particularly immune checkpoint inhibitor therapy. Identifying the key components of the gut microbiota that influence this response is paramount for designing therapeutic interventions to enhance the response to cancer therapy. This review will discuss strategies being considered to modulate the gut microbiota, including fecal microbiota transplantation, administration of defined bacterial isolates as well as bacterial consortia, supplementation with probiotics, and lifestyle modifications such as dietary changes. Understanding the influence of the complex variables of the human microbiota on the effectiveness of cancer therapy will help drive the clinical design of microbial-based interventions in the field of oncology.}, }
@article {pmid35756645, year = {2022}, author = {Chen, M and Liu, M and Li, C and Peng, S and Li, Y and Xu, X and Sun, M and Sun, X}, title = {Fecal Microbiota Transplantation Effectively Cures a Patient With Severe Bleeding Immune Checkpoint Inhibitor-Associated Colitis and a Short Review.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {913217}, doi = {10.3389/fonc.2022.913217}, pmid = {35756645}, issn = {2234-943X}, abstract = {Immune checkpoint inhibitors (ICIs) have opened up a new way for tumor therapy but simultaneously led to the occurrence of immune-related adverse events. We report a case of successful treatment of PD-1 inhibitor-associated colitis with fecal microbiota transplantation (FMT). The patient was a palatal malignant melanoma who developed diarrhea and hematochezia accompanied by fever, gastrointestinal bleeding, and infection after the third treatment with PD-1 (Toripalimab). The patient received general treatment unsuccessful, corticosteroid therapy after initial success but rapid loss of response, and finally successful treatment after fecal microbiota transplantation.}, }
@article {pmid35755849, year = {2022}, author = {Aira, A and Rubio, E and Ruiz, A and Vergara, A and Casals-Pascual, C and Rico, V and Suñé-Negre, JM and Soriano, A}, title = {New Procedure to Maintain Fecal Microbiota in a Dry Matrix Ready to Encapsulate.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {899257}, doi = {10.3389/fcimb.2022.899257}, pmid = {35755849}, issn = {2235-2988}, abstract = {Fecal microbiota transplantation (FMT) is one of the recommended treatments for recurrent Clostridioides difficile infection, but endoscopy and available oral formulations still have several limitations in their preparation, storage, and administration. The need for a viable oral formulation that facilitates the implementation of this highly effective therapy in different settings has led us to test the microcrystalline cellulose particles as an adsorbent of concentrated filtered fresh feces in comparison to lyophilized feces. This free-flowing material can provide protection to bacteria and results in a dried product able to maintain the viability of the microbiota for a long time. Adsorbate formulation showed a stabilizing effect in gut microbiota, maintaining bacteria viability and preserving its diversity, and is a competitive option for lyophilized capsules.}, }
@article {pmid35753395, year = {2022}, author = {Li, X and Xiao, F and Li, Y and Hu, H and Xiao, Y and Xu, Q and Li, D and Yu, G and Wang, Y and Zhang, T}, title = {Characteristics and management of children with Clostridiodes difficile infection at a tertiary pediatric hospital in China.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {}, number = {}, pages = {102380}, doi = {10.1016/j.bjid.2022.102380}, pmid = {35753395}, issn = {1678-4391}, abstract = {BACKGROUND: Clostridiodes difficile infection (CDI) is one of the most common causes of antibiotic-associated diarrhea in children. Conventional antibiotics and emerging fecal microbiota transplantation (FMT) are used to treat CDI.
METHODS: Children with CDI admitted to the Shanghai Children's Hospital, from September 2014 to September 2020, were retrospectively included to this observational study. Pediatric patients were assigned as initial CDI and recurrent CDI (RCDI), and symptoms, comorbidities, imaging findings, laboratory tests, and treatments were systematically recorded and analyzed.
RESULTS: Of 109 pediatric patients with CDI, 58 were boys (53.2%), and the median age was 5 years (range, 2-9 years). The main clinical symptoms of CDI children were diarrhea (109/109, 100%), hematochezia (55/109, 50.46%), abdominal pain (40/109, 36.70%); fever, pseudomembrane, vomit, and bloating were observed in 39 (35.78%), 33 (30.28%), and 24 (22.02%) patients, respectively. For the primary therapy with conventional antibiotics, 68 patients received metronidazole, and 41 patients received vancomycin. RCDI occurred in 48.53% (33/68) of those initially treated with metronidazole compared with 46.33% (19/41) of those initially treated with vancomycin (p=0.825). The total resolution rate of FMT for RCDI children was significantly higher than with vancomycin treatment (28/29, 96.55% vs 11/23, 47.83%, p < 0.001). There were no serious adverse events (SAEs) reported after two months of FMT.
CONCLUSIONS: The major manifestations of children with CDI were diarrhea, hematochezia, and abdominal pain. The cure rate of FMT for pediatric RCDI is superior to vancomycin treatment.}, }
@article {pmid35745257, year = {2022}, author = {Bian, J and Liebert, A and Bicknell, B and Chen, XM and Huang, C and Pollock, CA}, title = {Faecal Microbiota Transplantation and Chronic Kidney Disease.}, journal = {Nutrients}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/nu14122528}, pmid = {35745257}, issn = {2072-6643}, mesh = {*Clostridium Infections ; *Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation/methods ; Feces ; Humans ; Renal Dialysis ; *Renal Insufficiency, Chronic/therapy ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) has attracted increasing attention as an intervention in many clinical conditions, including autoimmune, enteroendocrine, gastroenterological, and neurological diseases. For years, FMT has been an effective second-line treatment for Clostridium difficile infection (CDI) with beneficial outcomes. FMT is also promising in improving bowel diseases, such as ulcerative colitis (UC). Pre-clinical and clinical studies suggest that this microbiota-based intervention may influence the development and progression of chronic kidney disease (CKD) via modifying a dysregulated gut-kidney axis. Despite the high morbidity and mortality due to CKD, there are limited options for treatment until end-stage kidney disease occurs, which results in death, dialysis, or kidney transplantation. This imposes a significant financial and health burden on the individual, their families and careers, and the health system. Recent studies have suggested that strategies to reverse gut dysbiosis using FMT are a promising therapy in CKD. This review summarises the preclinical and clinical evidence and postulates the potential therapeutic effect of FMT in the management of CKD.}, }
@article {pmid35739018, year = {2022}, author = {Carneiro, PV and Montenegro, NA and Lana, A and Amato, AA and Santos, GM}, title = {Lipids from gut microbiota: pursuing a personalized treatment.}, journal = {Trends in molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.molmed.2022.06.001}, pmid = {35739018}, issn = {1471-499X}, abstract = {The discovery of microbiome metabolites has enlivened the field of fecal transplantation for therapeutic purposes. However, the transfer of pathogenic living organisms was recently observed to limit its therapeutic potential by increasing the risk of infection. Lipids produced by gut microbiota enter the circulation and control many phenotypic changes associated with microbiota composition. Fecal lipids significantly impact the regulation of several cell signaling pathways, including inflammation. Focusing on these molecules, we review how bioactive gut microbiota-associated lipids affect cellular functioning and clinical outcome. Here, we interrogate whether the gut microbiota can be considered a cutting-edge biotechnological tool for rapid metabolic engineering of meaningful lipids to offer a novel personalized therapy.}, }
@article {pmid35751882, year = {2022}, author = {Liu, T and Li, YL and Zhou, LJ and Sun, XN and Wang, YL and Du, LJ and Liu, Y and Zhu, H and Chen, BY and Sun, JY and Liu, Y and Xu, S and Ye, HL and Huang, SJ and Wang, X and Li, B and Duan, SZ}, title = {Mineralocorticoid Receptor Deficiency in Treg Cells Ameliorates DSS-Induced Colitis in a Gut Microbiota-Dependent Manner.}, journal = {Immunology}, volume = {}, number = {}, pages = {}, doi = {10.1111/imm.13522}, pmid = {35751882}, issn = {1365-2567}, abstract = {Mineralocorticoid receptor (MR) is a classic nuclear receptor and an effective drug target in the cardiovascular system. The function of MR in immune cells such as macrophages and T cells has been increasingly appreciated. The aim of this study was to investigate the function of Treg MR in the process of inflammatory bowel disease (IBD). We treated Treg MR-deficient (MRflox/flox Foxp3YFP-Cre , KO) mice and control (Foxp3YFP-Cre , WT) mice with dextran sodium sulphate (DSS) to induce colitis and found that the severity of DSS-induced colitis was markedly alleviated in Treg MR-deficient mice, accompanied by reduced production of inflammatory cytokines, and relieved infiltration of monocytes, neutrophils and interferon γ+ T cells in colon lamina propria. Fecal microbiota of mice with colitis was analyzed by 16S rRNA gene sequencing and the composition of gut microbiota was vastly changed in Treg MR-deficient mice. Furthermore, depletion of gut microbiota by antibiotics abolished the protective effects of Treg MR deficiency and resulted in similar severity of DSS-induced colitis in WT and KO mice. Fecal microbiota transplantation from KO mice attenuated DSS-induced colitis characterized by alleviated inflammatory infiltration compared to that from WT mice. Hence, our study demonstrates that Treg MR deficiency protects against DSS-induced colitis by attenuation of colonic inflammatory infiltration. Gut microbiota is both sufficient and necessary for Treg MR deficiency to exert the beneficial effects.}, }
@article {pmid35748460, year = {2022}, author = {Catalán-Serra, I and Ricanek, P and Grimstad, T}, title = {"Out of the box" new therapeutic strategies for Crohn´s disease: moving beyond biologics.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {}, number = {}, pages = {}, doi = {10.17235/reed.2022.9010/2022}, pmid = {35748460}, issn = {1130-0108}, abstract = {New treatment options beyond immunosuppression have emerged in recent years for patients with Crohn´s disease (CD), a chronic systemic condition affecting primarily the gut with great impact in the quality of life. The cause of CD is largely unknown, and a curative treatment is not yet available. In addition, despite the growing therapeutic armamentarium in recent years almost half of the patients don´t achieve a sustained response over time. Thus, new therapeutic strategies are urgently needed. In this review, we discuss the current state of promising new "out of the box" possibilities to control chronic inflammation beyond current pharmacological treatments, including: exclusive enteral nutrition, specific diets, cell therapies using T regs, hyperbaric oxygen, fecal microbiota transplantation, phage therapy, helminths, cannabis and vagal nerve stimulation. The exploration of original and novel therapeutic modalities is key to address their potential as main or complementary treatments in selected CD populations in order to increase efficacy, minimize side effects and improve quality of life of patients.}, }
@article {pmid35745805, year = {2022}, author = {Yang, C and Sung, J and Long, D and Alghoul, Z and Merlin, D}, title = {Prevention of Ulcerative Colitis by Autologous Metabolite Transfer from Colitogenic Microbiota Treated with Lipid Nanoparticles Encapsulating an Anti-Inflammatory Drug Candidate.}, journal = {Pharmaceutics}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/pharmaceutics14061233}, pmid = {35745805}, issn = {1999-4923}, support = {RO1-DK-116306/DK/NIDDK NIH HHS/United States ; RO1-DK-107739/DK/NIDDK NIH HHS/United States ; 689659//Crohn's and Colitis Foundation/ ; BX004476//Atlanta VA Medical Center/ ; BX002526//Atlanta VA Medical Center/ ; }, abstract = {Modulating the gut microbiota composition is a potent approach to treat various chronic diseases, including obesity, metabolic syndrome, and ulcerative colitis (UC). However, the current methods, such as fecal microbiota transplantation, carry a risk of serious infections due to the transmission of multi-drug-resistant organisms. Here, we developed an organism-free strategy in which the gut microbiota is modulated ex vivo and microbiota-secreted metabolites are transferred back to the host. Using feces collected from the interleukin-10 (IL-10) knockout mouse model of chronic UC, we found that a drug candidate (M13)-loaded natural-lipid nanoparticle (M13/nLNP) modified the composition of the ex vivo-cultured inflamed gut microbiota and its secreted metabolites. Principal coordinate analysis (PCoA) showed that M13/nLNP shifted the inflamed microbiota composition toward the non-inflamed direction. This compositional modification induced significant changes in the chemical profiles of secreted metabolites, which proved to be anti-inflammatory against in vitro-cultured NF-κβ reporter cells. Further, when these metabolites were orally administered to mice, they established strong protection against the formation of chronic inflammation. Our study demonstrates that ex vivo modulation of microbiota using M13/nLNP effectively reshaped the microbial secreted metabolites and that oral transfer of these metabolites might be an effective and safe therapeutic approach for preventing chronic UC.}, }
@article {pmid35745496, year = {2022}, author = {Alam, MJ and Xie, L and Yap, YA and Marques, FZ and Robert, R}, title = {Manipulating Microbiota to Treat Atopic Dermatitis: Functions and Therapies.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, doi = {10.3390/pathogens11060642}, pmid = {35745496}, issn = {2076-0817}, support = {105663/WT_/Wellcome Trust/United Kingdom ; //Senior Medical Research Fellowship from the Sylvia and Charles Viertel Charitable Foundation/ ; //Monash Graduate Scholarship from Monash University, Australia/ ; }, abstract = {Atopic dermatitis (AD) is a globally prevalent skin inflammation with a particular impact on children. Current therapies for AD are challenged by the limited armamentarium and the high heterogeneity of the disease. A novel promising therapeutic target for AD is the microbiota. Numerous studies have highlighted the involvement of the skin and gut microbiota in the pathogenesis of AD. The resident microbiota at these two epithelial tissues can modulate skin barrier functions and host immune responses, thus regulating AD progression. For example, the pathogenic roles of Staphylococcus aureus in the skin are well-established, making this bacterium an attractive target for AD treatment. Targeting the gut microbiota is another therapeutic strategy for AD. Multiple oral supplements with prebiotics, probiotics, postbiotics, and synbiotics have demonstrated promising efficacy in both AD prevention and treatment. In this review, we summarize the association of microbiota dysbiosis in both the skin and gut with AD, and the current knowledge of the functions of commensal microbiota in AD pathogenesis. Furthermore, we discuss the existing therapies in manipulating both the skin and gut commensal microbiota to prevent or treat AD. We also propose potential novel therapies based on the cutting-edge progress in this area.}, }
@article {pmid35739196, year = {2022}, author = {Qiao, L and Zhang, X and Pi, S and Chang, J and Dou, X and Yan, S and Song, X and Chen, Y and Zeng, X and Zhu, L and Xu, C}, title = {Dietary supplementation with biogenic selenium nanoparticles alleviate oxidative stress-induced intestinal barrier dysfunction.}, journal = {NPJ science of food}, volume = {6}, number = {1}, pages = {30}, pmid = {35739196}, issn = {2396-8370}, support = {32072746//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Selenium (Se) is an essential micronutrient that promotes body health. Endemic Se deficiency is a major nutritional challenge worldwide. The low toxicity, high bioavailability, and unique properties of biogenic Se nanoparticles (SeNPs) allow them to be used as a therapeutic drug and Se nutritional supplement. This study was conducted to investigate the regulatory effects of dietary SeNPs supplementation on the oxidative stress-induced intestinal barrier dysfunction and its association with mitochondrial function and gut microbiota in mice. The effects of dietary SeNPs on intestinal barrier function and antioxidant capacity and its correlation with gut microbiota were further evaluated by a fecal microbiota transplantation experiment. The results showed that Se deficiency caused a redox imbalance, increased the levels of pro-inflammatory cytokines, altered the composition of the gut microbiota, and impaired mitochondrial structure and function, and intestinal barrier injury. Exogenous supplementation with biogenic SeNPs effectively alleviated diquat-induced intestinal barrier dysfunction by enhancing the antioxidant capacity, inhibiting the overproduction of reactive oxygen species (ROS), preventing the impairment of mitochondrial structure and function, regulating the immune response, maintaining intestinal microbiota homeostasis by regulating nuclear factor (erythroid-derived-2)-like 2 (Nrf2)-mediated NLR family pyrin domain containing 3 (NLRP3) signaling pathway. In addition, Se deficiency resulted in a gut microbiota phenotype that is more susceptible to diquat-induced intestinal barrier dysfunction. Supranutritional SeNPs intake can optimize the gut microbiota to protect against intestinal dysfunctions. This study demonstrates that dietary supplementation of SeNPs can prevent oxidative stress-induced intestinal barrier dysfunction through its regulation of mitochondria and gut microbiota.}, }
@article {pmid35737457, year = {2022}, author = {Rei, D and Saha, S and Haddad, M and Haider Rubio, A and Perlaza, BL and Berard, M and Ungeheuer, MN and Sokol, H and Lledo, PM}, title = {Age-associated gut microbiota impairs hippocampus-dependent memory in a vagus-dependent manner.}, journal = {JCI insight}, volume = {}, number = {}, pages = {}, doi = {10.1172/jci.insight.147700}, pmid = {35737457}, issn = {2379-3708}, abstract = {Aging is known to be associated with hippocampus-dependent memory decline, but the underlying causes of this age-related memory impairment remain yet highly debated. Here we showed that fecal microbiota transplantation (FMT) from aged, but not young, animal donors in young mice is sufficient to trigger profound hippocampal alterations including astrogliosis, decreased adult neurogenesis, decreased novelty-induced neuronal activation and impairment in hippocampus-dependent memory. Furthermore, similar alterations were reported when mice were subjected to an FMT from aged human donors. To decipher the mechanisms involved in mediating these microbiota-induced effects on brain function, we mapped the vagus nerve (VN)-related neuronal activity patterns and report that aged-mice FM transplanted animals showed a reduction in neuronal activity in the ascending VN output brain structure, whether under basal condition or after VN stimulation. Targeted pharmacogenetic manipulation of VN-ascending neurons demonstrated that the decrease in vagal activity is detrimental to hippocampal functions. In contrast, increasing vagal ascending activity alleviated the adverse effects of aged mice FMT on hippocampal functions, and had a pro-mnesic effect in aged mice. Thus, pharmacogenetic VN stimulation is a potential therapeutic strategy to lessen microbiota-dependent age-associated impairments in hippocampal functions.}, }
@article {pmid35721102, year = {2022}, author = {Zhang, J and Guo, Y and Duan, L}, title = {Features of Gut Microbiome Associated With Responses to Fecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {773105}, doi = {10.3389/fmed.2022.773105}, pmid = {35721102}, issn = {2296-858X}, abstract = {Fecal microbiota transplantation (FMT) has been seen as a novel treatment for inflammatory bowel disease (IBD). The results on microbial alterations and their relationship to treatment efficacy are varied among studies. We performed a systematic review to explore the association between microbial features and therapy outcomes. We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to November 2020. Studies that investigated the efficacy of FMT and baseline microbial features or dynamic alteration of the microbiome during FMT were included. The methodological quality of the included cohort studies and randomized controlled trials (RCTs) was assessed using the Newcastle-Ottawa Scale (NOS) and the Cochrane risk of bias tool, respectively. A total of 30 studies were included in the analysis. Compared to non-responders, the microbial structure of patients who responded to FMT had a higher similarity to that of their donors after FMT. Donors of responders (R-d) and non-responders (NR-d) had different microbial taxa, but the results were inconsistent. After FMT, several beneficial short-chain fatty acids- (SCFA-) producing taxa, such as Faecalibacterium, Eubacterium, Roseburia, and species belonging to them, were enriched in responders, while pathogenic bacteria (Escherichia coli and Escherichia-Shigella) belonging to the phylum Proteobacteria were decreased. Alterations of microbial functional genes and metabolites were also observed. In conclusion, the response to FMT was associated with the gut microbiota and their metabolites. The pre-FMT microbial features of recipients, the comparison of pre- and post-FMT microbiota, and the relationship between recipients and donors at baseline should be further investigated using uniform and standardized methods.}, }
@article {pmid35719863, year = {2022}, author = {Zhang, Y and Zhang, J and Pan, Z and He, X}, title = {Effects of Washed Fecal Bacteria Transplantation in Sleep Quality, Stool Features and Autism Symptomatology: A Chinese Preliminary Observational Study.}, journal = {Neuropsychiatric disease and treatment}, volume = {18}, number = {}, pages = {1165-1173}, doi = {10.2147/NDT.S355233}, pmid = {35719863}, issn = {1176-6328}, abstract = {Purpose: Autism spectrum disorder is a highly complex neurological and psychosocial disorder characterized by social dysfunction, severe reduction in speech, and a single stereotyped behavior. The treatment methods are currently limited, and children with autism generally suffer from constipation and sleep disorders. It is urgent to find an alternative psychotropic drug, given the drug dependence and adverse reactions that may occur with long-term medication.
Patients and Methods: This retrospective study included 49 children with autism at the first affiliated Hospital of Guangdong Pharmaceutical University, who received washed fecal microbiota transplantation (WMT) treatment between June 2019 and July 2021 and compared the sleep disorder scores between the constipation group, control group and blank group.
Results: Second WMT could significantly improve the sleep disorder scores in the constipation group (p=0.026) and the decrease in sleep disturbance scale for children (SDSC) score was synchronized with the increase in Bristol stool form scale (BSFS) score. However, there was no significant difference between patients without constipation (p=0.54), and the behavior of autism improved in both groups.
Conclusion: WMT could relieve constipation and improve sleep disorders in children with autism, with no deterioration in stool morphology and sleep disorders in other children. Moreover, there were no obvious serious adverse clinical events after WMT.}, }
@article {pmid35719145, year = {2022}, author = {Tan, J and Gong, J and Liu, F and Li, B and Li, Z and You, J and He, J and Wu, S}, title = {Evaluation of an Antibiotic Cocktail for Fecal Microbiota Transplantation in Mouse.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {918098}, doi = {10.3389/fnut.2022.918098}, pmid = {35719145}, issn = {2296-861X}, abstract = {Objective: This study aimed to evaluate the effect of an antibiotic cocktail on gut microbiota and provide a reference for establishing an available mouse model for fecal microbiota transplantation (FMT) of specific microbes.
Design: C57BL/6J mice (n = 24) had free access to an antibiotic cocktail containing vancomycin (0.5 g/L), ampicillin (1 g/L), neomycin (1 g/L), and metronidazole (1 g/L) in drinking water for 3 weeks. Fecal microbiota was characterized by 16S rDNA gene sequencing at the beginning, 1st week, and 3rd week, respectively. The mice were then treated with fecal microbiota from normal mice for 1 week to verify the efficiency of FMT.
Results: The diversity of microbiota including chao1, observed species, phylogenetic diversity (PD) whole tree, and Shannon index were decreased significantly (P < 0.05) after being treated with the antibiotic cocktail for 1 or 3 weeks. The relative abundance of Bacteroidetes, Actinobacteria, and Verrucomicrobia was decreased by 99.94, 92.09, and 100%, respectively, while Firmicutes dominated the microbiota at the phylum level after 3 weeks of treatment. Meanwhile, Lactococcus, a genus belonging to the phylum of Firmicutes dominated the microbiota at the genus level with a relative abundance of 80.63%. Further FMT experiment indicated that the fecal microbiota from the receptor mice had a similar composition to the donor mice after 1 week.
Conclusion: The antibiotic cocktail containing vancomycin, ampicillin, neomycin, and metronidazole eliminates microbes belonging to Bacteroidetes, Actinobacteria, and Verrucomicrobia, which can be recovered by FMT in mice.}, }
@article {pmid35719141, year = {2022}, author = {Zhao, HJ and Zhang, XJ and Zhang, NN and Yan, B and Xu, KK and Peng, LH and Pan, F}, title = {Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {890357}, doi = {10.3389/fnut.2022.890357}, pmid = {35719141}, issn = {2296-861X}, abstract = {Background: Gut microbiota has been identified as an imbalance in patients with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is a novel method to restore microbiota and treat IBS patients.
Objective: To conduct a meta-analysis and estimate the efficacy and safety of FMT for the treatment of IBS patients with subgroup analyses to explore the most effective way of FMT for IBS.
Methods: All eligible studies were searched from PubMed, Embase, Web of Science, and the Cochrane Library through multiple search strategies. Data were extracted from studies comprising the following criteria: double-blind, randomized controlled trials (RCTs) that compared the efficacy of FMT with placebo for adult patients (≥18 years old) with IBS. A meta-analysis was performed to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs).
Results: A total of seven RCTs comprising 489 subjects were eligible for this meta-analysis. Pooled data showed no significant improvement of global IBS symptoms in patients with FMT compared with placebo (RR = 1.34; 95% CI 0.75-2.41, p = 0.32). A significant heterogeneity was observed among the studies (I 2 = 83%, p < 0.00001). There was no significant evidence of funnel plot asymmetry (Egger's test, p = 0.719; Begg's test, p = 1.000), indicating no existence of publication bias. Subgroup analyses revealed that FMT operated by invasive routes, including gastroscope, colonoscope, and nasojejunal tube, significantly improved global IBS symptoms (RR = 1.96; 95% CI 1.23-3.11, p = 0.004) with heterogeneity (I 2 = 57%, p = 0.06) and an NNT of 3 (95% CI 2-14). However, FMT delivered via oral capsules showed a negative impact on patients with IBS (RR = 0.56; 95% CI 0.33-0.96, p = 0.03) with a low heterogeneity (I 2 = 39%, p = 0.2) and an NNH of 3 (95% CI 2-37).
Conclusion: The current evidence from RCTs with all routes of FMT does not show significant global improvement in patients with IBS. However, FMT operated by invasive routes significantly improved global IBS symptoms.}, }
@article {pmid35716734, year = {2022}, author = {Qu, Z and Tian, P and Yang, B and Zhao, J and Wang, G and Chen, W}, title = {Fecal microbiota transplantation for diseases: Therapeutic potential, methodology, risk management in clinical practice.}, journal = {Life sciences}, volume = {}, number = {}, pages = {120719}, doi = {10.1016/j.lfs.2022.120719}, pmid = {35716734}, issn = {1879-0631}, abstract = {BACKGROUND: More than 95 % of human diseases may be related to the disturbance of gut microbes. As a treatment method that extensively regulates the gut microbes, fecal microbiota transplantation (FMT) has proven to be an effective therapy for some diseases, becoming a topic of interest among clinicians, patients and scientists.
AIM: To review the latest clinical research results of FMT in the treatment of various diseases and the methodology and risk management in clinical application.
METHODS: Search PubMed and Web of Science for reliable research results of clinical treatment of FMT within 5-10 years, as well as application guidelines and risk management policies in different regions.
RESULTS: As a measure of allogeneic/autologous microbiota transplantation, FMT has been used to treat a variety of diseases. By reviewing the clinical studies of FMT in gastrointestinal diseases, metabolic diseases, neurological diseases and malignant tumors, the various mechanisms in the treatment of diseases are summarized. Such as regulation of receptor microbiota composition, specific metabolites, phage function and immune response. In addition, potential risk factors, donor stool screening indicators, recipient self-specificity and possible prognostic marker molecules in the course of FMT treatment were generalized.
CONCLUSIONS: The potential regulatory mechanisms, risk factors and targets of FMT in gastrointestinal diseases, metabolic diseases, malignancies and neurological diseases were reviewed and proposed. It provides a theoretical basis for the establishment of a standardized treatment system for FMT and a breakthrough in treatment technology.}, }
@article {pmid35709819, year = {2022}, author = {Mullish, BH and McDonald, JAK and Marchesi, JR}, title = {Intestinal microbiota transplantation: do not forget the metabolites.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {7}, number = {7}, pages = {594}, doi = {10.1016/S2468-1253(22)00101-7}, pmid = {35709819}, issn = {2468-1253}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid35580364, year = {2022}, author = {Thakur, S and Sheppard, JD}, title = {Gut Microbiome and Its Influence On Ocular Surface and Ocular Surface Diseases.}, journal = {Eye & contact lens}, volume = {48}, number = {7}, pages = {278-282}, doi = {10.1097/ICL.0000000000000905}, pmid = {35580364}, issn = {1542-233X}, mesh = {Ecosystem ; *Eye Diseases/prevention & control ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {ABSTRACT: The gut microbiome plays a substantial immunologic and pathophysiologic role in maintaining the health of the host, and dysregulation of this dynamic ecosystem has been associated with several inflammatory conditions. Many studies have explored the influence of gut microbiota on the ocular surface and whether gut microbiota impact the pathophysiology of ophthalmic conditions. These findings have highlighted the advantages of enhancing gut microbes through probiotics, prebiotics, diet, vitamin supplementations, and fecal microbial transplant in clinical practice. The purpose of this review article was to provide an up-to-date overview of the knowledge on this topic. Further exploration of this area of research is important to help guide new therapeutic targets to develop treatment and prevention of certain ocular surface diseases.}, }
@article {pmid35711246, year = {2022}, author = {Liu, Y and Chen, M}, title = {Clostridioides difficile Infection in Liver Cirrhosis: A Concise Review.}, journal = {Canadian journal of gastroenterology & hepatology}, volume = {2022}, number = {}, pages = {4209442}, doi = {10.1155/2022/4209442}, pmid = {35711246}, issn = {2291-2797}, mesh = {*Clostridioides difficile ; *Clostridium Infections/epidemiology/prevention & control ; Fecal Microbiota Transplantation/methods ; Humans ; Liver Cirrhosis/complications/therapy ; Recurrence ; Rifaximin ; Treatment Outcome ; }, abstract = {Clostridium difficile is a Gram-positive bacillus with fecal-oral transmission and is currently one of the most common nosocomial infections worldwide, which was renamed Clostridioides difficile in 2016. Clostridioides difficile infection (CDI) is a prevalent infection in cirrhosis and negatively affects prognosis. This study aimed to provide a concise review with clinical practice implications. The prevalence of CDI in cirrhotic patients increases, while the associated mortality decreases. Multiple groups of risk factors increase the likelihood of CDI in patients with cirrhosis, such as antibiotic use, the severity of cirrhosis, some comorbidities, and demographic aspects. Treatment in the general population is currently described in the latest guidelines. In patients with cirrhosis, rifaximin and lactulose have been shown to reduce CDI risk due to their modulatory effects on the intestinal flora, although conflicting results exist. Fecal microbiota transplantation (FMT) as a treatment for the second or subsequent CDI recurrences has demonstrated a good safety and efficacy in cirrhosis and CDI. Future validation in more prospective studies is needed. Screening of asymptomatic patients appears to be discouraged for the prevention currently, with strict hand hygiene and cleaning of the ward and medical equipment surfaces being the cornerstone of minimizing transmission.}, }
@article {pmid35710492, year = {2022}, author = {Zhong, W and Wu, K and Long, Z and Zhou, X and Zhong, C and Wang, S and Lai, H and Guo, Y and Lv, D and Lu, J and Mao, X}, title = {Gut dysbiosis promotes prostate cancer progression and docetaxel resistance via activating NF-κB-IL6-STAT3 axis.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {94}, pmid = {35710492}, issn = {2049-2618}, support = {82173039//National Natural Science Foundation of China/ ; 81773277//National Natural Science Foundation of China/ ; 82003271//National Natural Science Foundation of China/ ; 201803010014//Science and Technology Plan Project of Guangzhou/ ; 202102010150//Science and Technology Plan Project of Guangzhou/ ; 202102080010//Science and Technology Plan Project of Guangzhou/ ; 2021A1515010659//Guangdong Province Basic and Applied Basic Research Foundation/ ; 2020A1515110922//Guangdong Province Basic and Applied Basic Research Foundation/ ; 2019A1515110033//Guangdong Province Basic and Applied Basic Research Foundation/ ; 2019M662865//China Postdoctoral Science Foundation/ ; 2019KQNCX115//Distinguished Young Talents in Higher Education Foundation of Guangdong Province/ ; ZH201908//Achievement cultivation and clinical transformation application cultivation projects of the First Affiliated Hospital of Guangzhou Medical University/ ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Docetaxel/pharmacology ; *Dysbiosis/microbiology ; Feces/microbiology ; Humans ; Interleukin-6 ; Lipopolysaccharides ; Male ; Mice ; NF-kappa B ; *Prostatic Neoplasms ; Proteobacteria/genetics ; RNA, Ribosomal, 16S/genetics ; STAT3 Transcription Factor/genetics ; }, abstract = {BACKGROUND: The gut microbiota is reportedly involved in the progression and chemoresistance of various human malignancies. However, the underlying mechanisms behind how it exerts some effect on prostate cancer, as an extra-intestinal tumor, in a contact-independent way remain elusive and deserve exploration. Antibiotic exposure, one of the various factors affecting the gut microbiota community and capable of causing gut dysbiosis, is associated with multiple disorders. This study aims to preliminarily clarify the link between gut dysbiosis and prostate cancer.
RESULTS: First, we discovered that perturbing the gut microbiota by consuming broad-spectrum antibiotics in water promoted the growth of subcutaneous and orthotopic tumors in mice. Fecal microbiota transplantation could transmit the effect of antibiotic exposure on tumor growth. Then, 16S rRNA sequencing for mouse feces indicated that the relative abundance of Proteobacteria was significantly higher after antibiotic exposure. Meanwhile, intratumoral lipopolysaccharide (LPS) profoundly increased under the elevation of gut permeability. Both in vivo and in vitro experiments revealed that the NF-κB-IL6-STAT3 axis activated by intratumoral LPS facilitated prostate cancer proliferation and docetaxel chemoresistance. Finally, 16S rRNA sequencing of patients' fecal samples revealed that Proteobacteria was enriched in patients with metastatic prostate cancer and was positively correlated with plasma IL6 level, regional lymph node metastasis status, and distant metastasis status. The receiver operating characteristic (ROC) curves showed that the relative abundance of Proteobacteria had better performance than the prostate-specific antigen (PSA) level in predicting the probability of distant metastasis in prostate cancer (area under the ROC curve, 0.860; p < 0.001).
CONCLUSION: Collectively, this research demonstrated that gut dysbiosis, characterized by the enrichment of Proteobacteria due to antibiotic exposure, resulted in the elevation of gut permeability and intratumoral LPS, promoting the development of prostate cancer via the NF-κB-IL6-STAT3 axis in mice. Considering findings from human patients, Proteobacteria might act as an intestinal biomarker for progressive prostate cancer. Video Abstract.}, }
@article {pmid35710014, year = {2022}, author = {Wen, S and Zhao, Y and Liu, S and Chen, Y and Yuan, H and Xu, H}, title = {Polystyrene microplastics exacerbated liver injury from cyclophosphamide in mice: Insight into gut microbiota.}, journal = {The Science of the total environment}, volume = {840}, number = {}, pages = {156668}, doi = {10.1016/j.scitotenv.2022.156668}, pmid = {35710014}, issn = {1879-1026}, abstract = {Microplastics (MPs) have infiltrated human food system globally, and the latent health risks have been well-described. However, the impact of pre-consumed MPs on liver resistance to foreign robust stimuli remains unclear. In this study, we developed a mouse model drinking roughly 18 and 180 μg/kg/day polystyrene MPs for 90 days, then intraperitoneally injected mice with 80 mg/kg cyclophosphamide (CTX) to investigate whether chronic pre-exposure to MPs aggravates hepatoxicity induced by CTX. Slight liver injury was found in single CTX-treated mice, while more significant liver histopathological damage, inflammation and oxidative stress elicited by CTX were observed in pre-drinking MPs mice. Moreover, chronic exposure of MPs induced remarkable colonic impairments (e.g., leaky gut, mild inflammation and repressed antioxidant activity) as well as gut microbiota perturbation, which manifested positive association with aggravated hepatotoxicity via spearman correlation analysis. Fecal microbiota transplantation (FMT) trail was conducted to ulteriorly demonstrate the critical role of MPs-altered gut bacteria in exaggerated liver susceptibility to CTX stimulation. In conclusion, our study provided an insight that the adverse impact of MPs could be best revealed when animals suffering attack from hazardous substance. It also contributes to comprehensive assessment of health risk from environmentally pervasive MPs.}, }
@article {pmid35709830, year = {2022}, author = {El-Salhy, M and Winkel, R and Casen, C and Hausken, T and Gilja, OH and Hatlebakk, JG}, title = {Efficacy of fecal microbiota transplantation for patients with irritable bowel syndrome at three years after transplantation.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2022.06.020}, pmid = {35709830}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: The long-term efficacy and possible adverse events of fecal microbiota transplantation (FMT) for IBS are unknown. This study performed a 3-year follow-up of the patients in our previous clinical trial to clarify these aspects.
METHODS: This study included 125 patients (104 females, and 21 males): 38 in a placebo group, 42 who received 30 g of donor feces, and 45 who received 60 g of donor feces. Feces was administered to the duodenum. The patients provided a fecal sample and completed five questionnaires at baseline and at 2 and 3 years after FMT. Fecal bacteria and dysbiosis index (DI) were analyzed using 16S rRNA gene PCR DNA amplification/probe hybridization covering the V3-V9 regions.
RESULTS: Response rates were 26.3%, 69.1%, and 77.8% in the placebo, 30-g, and 60-g groups, respectively, at 2 years after FMT, and 27.0%, 64.9%, and 71.8%, respectively, at 3 years after FMT. The response rates were significantly higher in the 30-g and 60-g groups than in the placebo group. Patients in the 30-g and 60-g groups had significantly fewer IBS symptoms and fatigue, and a greater quality of life both at 2 and 3 years after FMT. The DI decreased only in the active treatment groups at 2 and 3 years after FMT. Fluorescent signals of 10 bacteria had significant correlations with IBS symptoms and fatigue after FMT in the 30-g and 60-g groups. No long-term adverse events were recorded.
CONCLUSIONS: FMT performed according to our protocol resulted in high response rates and long-standing effects with only few mild self-limited adverse events.}, }
@article {pmid35698418, year = {2022}, author = {Zhou, W and Yang, T and Xu, W and Huang, Y and Ran, L and Yan, Y and Mi, J and Lu, L and Sun, Y and Zeng, X and Cao, Y}, title = {The polysaccharides from the fruits of Lycium barbarum L. confer anti-diabetic effect by regulating gut microbiota and intestinal barrier.}, journal = {Carbohydrate polymers}, volume = {291}, number = {}, pages = {119626}, doi = {10.1016/j.carbpol.2022.119626}, pmid = {35698418}, issn = {1879-1344}, abstract = {The antidiabetic effect and potential mechanisms of the polysaccharides from the fruits of Lycium barbarum L. (LBPs) by the mouse model of high-fat diet/streptozotocin-induced diabetes were investigated. Six-week oral administration of LBPs (200 mg/kg/day) resulted in improvement in the levels of fasting blood glucose (13.51% decrease) and glycated hemoglobin and β-cell function in diabetic mice, and simultaneously induced a 3.3-fold increment in one taxon belonging to genus Allobaculum in gut bacterial community. The experiments of fecal microbiota transplantation and antibiotics treatment confirmed that the LBPs-mediated gut microbiota participated in the glycemic control of the diabetes management. Moreover, LBPs intervention guarded the intestinal barrier function via upregulating the expression of zonula occludens 1 both in vivo (analyzing the gut permeability in diabetic mice) and in vitro (using intestinal-like Caco-2/RAW264.7 cells co-culture inflammation model). Collectively, our study showed that LBPs could confer anti-diabetic effect through modifying gut microbiota and intestinal barrier.}, }
@article {pmid35697204, year = {2022}, author = {Kattner, AA}, title = {A finger in every pie - the versatility of chemokines.}, journal = {Biomedical journal}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bj.2022.06.001}, pmid = {35697204}, issn = {2320-2890}, abstract = {In this issue of Biomedical Journal we encounter the chemokine superfamily and its clinical potential. The time course from 56 days zero COVID-19 to a resurgence in cases is presented, as well as a possible solution to overcome rejection in vascularized composite allotransplantation. We are shown the opportunity deep learning (DL) offers in the case of tracking single cells and particles, and also use of DL to bring all hands on deck to counter the current challenge of the COVID-19 pandemic. This issue contains articles about the effect of low energy shock waves in cystitis; the negative effect of high fructose on aortic valve stenosis; a study about the outcome of fecal microbiota transplantation in case of refractory Clostridioides difficile infection; a novel long non-coding RNA that could serve in treating triple-negative breast cancer; the benefits of acupressure in patients with restless leg syndrome; and Filamin A mutations in abnormal neuronal migration development. Finally, a link between jaw surgery and the psychological impact on the patient is explored; a method presented that allows identification of cervical characteristics associated with difficult embryo transfer; and a letter suggesting new parameters to evaluate the use of bone-substitute augmentation in the treatment of osteoporotic intertrochanteric fractures.}, }
@article {pmid35695221, year = {2022}, author = {Liu, T and Su, D and Lei, C and Liu, Z}, title = {Treatment of Radiation Enteritis With Fecal Transplantation.}, journal = {The American surgeon}, volume = {}, number = {}, pages = {31348221091954}, doi = {10.1177/00031348221091954}, pmid = {35695221}, issn = {1555-9823}, abstract = {Radiation enteritis (RE) is a frequent complication in patients who undergo pelvic irradiation, and this condition has been increasingly diagnosed. Fecal microbiota transplantation (FMT) is being developed in recent years, and it has remarkable curative effect for the clostridium and inflammatory bowel disease. Herein, we present a case of recurrent RE in a 59-year-old woman with RE 18 years after radiotherapy for cervical carcinoma. Fecal microbiota transplantation therapy with intestinal flora from her 18-year-old son was applied and was successful in relieving the symptoms. To the best of our knowledge, this study is the first case report of FMT in a patient with RE.}, }
@article {pmid35694271, year = {2022}, author = {Cai, M and Xiao, Y and Lin, Z and Lu, J and Wang, X and Rahman, SU and Zhu, S and Chen, X and Gu, J and Ma, Y and Chen, Z and Huo, J}, title = {Disordered Gut Microbiota in Colorectal Tumor-Bearing Mice Altered Serum Metabolome Related to Fufangchangtai.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {889181}, doi = {10.3389/fphar.2022.889181}, pmid = {35694271}, issn = {1663-9812}, abstract = {Purpose: This study aimed to investigate the relationship between gut microbiota (GM) and serum metabolism using antineoplastic Fufangchangtai (FFCT) as the model prescription in the treatment of colorectal cancer (CRC). Methods: Tumor-bearing mice and normal mice were administered different doses of FFCT. The tumor volume of tumor-bearing mice was observed. The levels of CD4+ and CD8+ T cells in the blood, spleen, and tumor of mice were determined using a flow cytometer. The bacterial microbiota in stool samples from mice and the serum metabolomics of FFCT-treated mice and fecal microbiota transplantation mice were detected using 16s RNA sequencing and liquid chromatography-mass spectrometry (LC/MS), respectively. Results: The tumor volume of mice showed no significant decrease after FFCT intervention. The levels of CD4+ and CD8+T lymphocytes showed a significant increase under the intervention of FFCT. GM of colorectal tumor-bearing mice and healthy mice were determined, and the diversity and abundance of Firmicutes, Deferribacteres, Bacteroidetes, and Proteobacteria were significantly different between the two groups. Furthermore, we found that the levels of matrine, isogingerenone B, and armillaripin were significantly decreased in tumor-bearing mice after FFCT intervention, indicating that the tumor-induced dysbiosis of gut bacteria may affect the absorption and metabolism of FFCT. Under the intervention of FFCT, serum metabolism of mice transplanted with feces from CRC patients showed less metabolites related to FFCT than that from healthy people, indicating that GM could be a single factor affecting the metabolism of FFCT. Furthermore, we found that different doses of FFCT-treated mice had higher abundance of Roseburia, Turicibacter, and Flexispira than that in the non-intervention control group. Firmicutes and Bacteroidetes in FFCT-treated groups showed a similar trend compared to the healthy group, indicating that FFCT might correct the intestinal microenvironment by modulating gut microbiota in colorectal tumor-bearing mice. Conclusion: The dysbiosis of GM in tumor-bearing mice reduced the serum metabolites related to FFCT, and FFCT could correct the disordered GM of colorectal tumor-bearing mice to exert efficacy.}, }
@article {pmid35693372, year = {2022}, author = {Gupta, K and Tappiti, M and Nazir, AM and Koganti, B and Memon, MS and Aslam Zahid, MB and Shantha Kumar, V and Mostafa, JA}, title = {Fecal Microbiota Transplant in Recurrent Clostridium Difficile Infections: A Systematic Review.}, journal = {Cureus}, volume = {14}, number = {5}, pages = {e24754}, doi = {10.7759/cureus.24754}, pmid = {35693372}, issn = {2168-8184}, abstract = {Fecal Microbiota Transplantation (FMT) is the process of transferring the fecal microbiome from a healthy donor to an individual with repeated multiple episodes of Clostridium difficile infection. It is also known as stool transplant. Fecal microbiota transplant is effective and safe in various studies, the approval from the Food and Drug Administration (FDA) remains pending. The main objective of this systemic review is to evaluate the efficacy and safety of stool transplant in studies with only treatment groups (FMT) and studies with treatment (FMT) and antibiotic (AB) groups and previous studies. Online databases PubMed, PubMed Central, Science Direct, Google Scholar, and Embase were searched for relevant articles in the last five years (2016 to 2021) using automation tools. Following the removal of duplicates, screening of eligibility criteria, titles/abstracts, and quality appraisal were done by two authors independently. In total, seven observational studies are in this review article. Out of the seven observational studies, five are retrospective and two prospective. Two of the five retrospective and one of two prospective studies have a control group. In both the prospective studies and one retrospective study, FMT efficacy of (68% to 93%) was demonstrated in the elderly population despite high index comorbidities. In the younger individuals with inflammatory bowel disease, and efficacy of 90% or above was found. The most common side effects were minor such as fever, abdominal pain, bloating, and flatulence. In one study, two cases of aspiration events occurred attributed to the gastroscopy route of donor feces delivery. There was no statistical significance in the incidence of diseases such as (allergies, autoimmune diseases, cancer, inflammatory bowel diseases, and neurological diseases like dementia and migraine). Fecal microbiota transplantation has shown to be effective and safe in recurrent Clostridium difficile infections. Since very few pragmatic studies have demonstrated its efficacy and safety, their application is not well established. Robust studies, both observation and experiment, are required in the future to well-establish its effectiveness, safety in the treatment of recurrent Clostridium difficile infection.}, }
@article {pmid35691195, year = {2022}, author = {Li, T and Tian, D and Lu, M and Wang, B and Li, J and Xu, B and Chen, H and Wu, S}, title = {Gut microbiota dysbiosis induced by polychlorinated biphenyl 126 contributes to increased brain proinflammatory cytokines: Landscapes from the gut-brain axis and fecal microbiota transplantation.}, journal = {Ecotoxicology and environmental safety}, volume = {241}, number = {}, pages = {113726}, doi = {10.1016/j.ecoenv.2022.113726}, pmid = {35691195}, issn = {1090-2414}, abstract = {The pathogenesis of brain inflammation induced by polychlorinated biphenyl 126 (PCB126) has not yet been fully illustrated. Growing evidence highlights the relevance of the microbiota-gut-brain axis in central nervous system (CNS) dysfunction. Therefore, we aimed to study the role of the gut microbiota in PCB126-induced proinflammatory cytokine increases in the mouse brain. The results showed that PCB126 exposure significantly disordered gut bacterial communities, resulting in the enrichment of gram-negative bacteria (e.g., Bacteroidetes and Proteobacteria), further leading to elevated levels of the gram-negative bacterial lipopolysaccharide (LPS). Subsequently, colonic toll-like receptor 4 (TLR-4) was activated by bacterial LPS, which promoted proinflammatory cytokine generation and inhibited tight junction (TJ) protein expression. Then, bacterial LPS translocated from the gut lumen into the blood circulation and reached the brain, triggering LPS/TLR-4-mediated increases in brain proinflammatory cytokines. Further analysis after fecal microbiota transplantation (FMT) suggested that the gut microbiota disturbance caused by PCB126 could induce elevated bacterial LPS and trigger TLR-4-mediated increases in proinflammatory cytokines in the brain. This study highlights the possibility that PCB126-induced gut microbiota disorder contributes to increased brain proinflammatory cytokines. These results provide a new perspective for identifying the toxicity mechanisms of PCB126 and open up the possibility of modulating the gut microbiota as a therapeutic target for CNS disease caused by environmental pollution.}, }
@article {pmid35690527, year = {2022}, author = {Huang, C and Yi, P and Zhu, M and Zhou, W and Zhang, B and Yi, X and Long, H and Zhang, G and Wu, H and Tsokos, GC and Zhao, M and Lu, Q}, title = {Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial.}, journal = {Journal of autoimmunity}, volume = {}, number = {}, pages = {102844}, doi = {10.1016/j.jaut.2022.102844}, pmid = {35690527}, issn = {1095-9157}, abstract = {Gut microbiota dysbiosis is involved in the development of systemic lupus erythematosus (SLE). The safety and efficacy of fecal microbiota transplantation (FMT) for the treatment of SLE patients has not been explored. In this 12-week, single-arm pilot clinical trial of oral encapsulated fecal microbiome from healthy donors to patients with active SLE, we aimed to evaluate the safety and efficacy of FMT in patients with SLE (ChiCTR2000036352). 20 SLE patients with SLEDAI ≥6 were recruited. FMT was administered once a week for three consecutive weeks along with standard treatment and the patients were followed for 12 weeks. Safety was evaluated throughout the trial. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. Microbiome composition, levels of short chain fatty acids (SCFAs) in the gut and of cytokines in the sera were measured along with lymphocyte phenotyping. No serious adverse events were observed after FMT. At week 12, the SRI-4 response rate was 42.12%, and significant reductions in the SLEDAI-2K scores and the level of serum anti-dsDNA antibody were observed compared to baseline. Significant enrichment of SCFAs-producing bacterial taxa and reduction of inflammation-related bacterial taxa were observed, along with increased production of SCFAs in the gut and reduced levels of IL-6 and CD4+ memory/naïve ratio in the peripheral blood. Furthermore, SRI-4 responding patients displayed specific microbiota signatures both before and after FMT. The first clinical trial of FMT in active SLE patients provide supportive evidence that FMT might be a feasible, safe, and potentially effective therapy in SLE patients by modifying the gut microbiome and its metabolic profile.}, }
@article {pmid35690329, year = {2022}, author = {Gu, Y and Wang, C and Qin, X and Zhou, B and Liu, X and Liu, T and Xie, R and Liu, J and Wang, B and Cao, H}, title = {Saccharomyces boulardii, a yeast probiotic, inhibits gut motility through upregulating intestinal serotonin transporter and modulating gut microbiota.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106291}, doi = {10.1016/j.phrs.2022.106291}, pmid = {35690329}, issn = {1096-1186}, abstract = {Saccharomyces boulardii (Sb) is a widely used fungal probiotic in treating various digestive diseases, including irritable bowel syndrome (IBS). However, the specific mechanisms of Sb relieving IBS remain unclear. The abnormal serotonin transporter (SERT) / 5-hydroxytryptamine (5-HT) system could cause disordered gastrointestinal sensation and motility, which closely related to IBS pathogenesis. The aim of this study was to explore the effects and mechanisms of Sb on regulating gut motility. Sb supernatant (SbS) was administered to intestinal epithelial cells and mice. SbS upregulated SERT expression via enhancing heparin-binding epidermal growth factor (HB-EGF) release to activate epidermal growth factor receptor (EGFR). EGFR kinase inhibitor treatment or HB-EGF siRNA transfection in cells blocked SbS upregulating SERT. Consistently, SbS-treated mice presented inhibited gut motility, and EGFR activation and SERT upregulation were found. Moreover, 16S rDNA sequence presented an evident decrease in Firmicutes / Bacteroidetes ratio in SbS group. In genus level, SbS reduced Escherichia_Shigella, Alistipes, Clostridium XlVa, and Saccharibacteria_genera_incertae_sedis, meanwhile, increased Parasutterella. The abundance of Saccharibacteria_genera_incertae_sedis positively correlated with defecation parameters and intestinal 5-HT content. Fecal microbiota transplantation showed that SbS could modulate gut microbiota to influence gut motility. Interestingly, elimination of gut microbiota with antibiotic cocktail did not entirely block SbS regulating gut motility. Furthermore, SbS administration to IBS-D mice significantly upregulated SERT and inhibited gut motility. In conclusion, SbS could upregulate SERT by EGFR activation, and modulate gut microbiota to inhibit gut motility. This finding would provide more evidence for the application of this yeast probiotic in IBS and other diarrheal disorders.}, }
@article {pmid35688268, year = {2022}, author = {Zhang, KK and Liu, JL and Chen, LJ and Li, JH and Yang, JZ and Xu, LL and Chen, YK and Zhang, QY and Li, XW and Liu, Y and Zhao, D and Xie, XL and Wang, Q}, title = {Gut microbiota mediates methamphetamine-induced hepatic inflammation via the impairment of bile acid homeostasis.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {}, number = {}, pages = {113208}, doi = {10.1016/j.fct.2022.113208}, pmid = {35688268}, issn = {1873-6351}, abstract = {Methamphetamine (Meth), an addictive psychostimulant of abuse worldwide, has been a common cause of acute toxic hepatitis in adults. Gut microbiota has emerged as a modulator of host immunity via metabolic pathways. However, the microbial mechanism of Meth-induced hepatic inflammation and effective therapeutic strategies remain unknown. Here, mice were intraperitoneally (i.p.) injected with Meth to induce hepatotoxicity. Cecal microbiome and bile acids (BAs) composition were analysed after Meth administration. Fecal microbiota transplantation (FMT) technology was utilized to investigate the role of microbiota. Additionally, the protective effects of obeticholic acid (OCA), an agonist of farnesoid X receptor (FXR), were evaluated. Results indicated that Meth administration induced hepatic cholestasis, dysfunction and aroused hepatic inflammation by stimulating the TLR4/MyD88/NF-κB pathway in mice. Meanwhile, Meth disturbed the cecal microbiome and impaired the homeostasis of BAs. Interestingly, FMT from Meth administered mice resulted in serum and hepatic BA accumulation and transferred similar phenotypic changes into the healthy recipient mice. Finally, OCA normalized Meth-induced BA accumulation in both serum and the liver, and effectively protected against Meth-induced hepatic dysfunction and inflammation by suppressing the TLR4/MyD88/NF-κB pathway. This study established the importance of microbial mechanism and its inhibition as a potential therapeutic target to treat Meth-related hepatotoxicity.}, }
@article {pmid35681702, year = {2022}, author = {Sampsell, K and Wang, W and Ohland, C and Mager, LF and Pett, N and Lowry, DE and Sales, KM and McNeely, ML and McCoy, KD and Culos-Reed, SN and Reimer, RA}, title = {Exercise and Prebiotic Fiber Provide Gut Microbiota-Driven Benefit in a Survivor to Germ-Free Mouse Translational Model of Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {11}, pages = {}, doi = {10.3390/cancers14112722}, pmid = {35681702}, issn = {2072-6694}, support = {VPR Catalyst Grant//University of Calgary/ ; Cancer Prevention Research Opportunity//Alberta Innovates/ ; Grant//Alberta Cancer Foundation/ ; }, abstract = {The gut microbiota plays a role in shaping overall host health and response to several cancer treatments. Factors, such as diet, exercise, and chemotherapy, can alter the gut microbiota. In the present study, the Alberta Cancer Exercise (ACE) program was investigated as a strategy to favorably modify the gut microbiota of breast cancer survivors who had received chemotherapy. Subsequently, the ability of post-exercise gut microbiota, alone or with prebiotic fiber supplementation, to influence breast cancer outcomes was interrogated using fecal microbiota transplant (FMT) in germ-free mice. While cancer survivors experienced little gut microbial change following ACE, in the mice, tumor volume trended consistently lower over time in mice colonized with post-exercise compared to pre-exercise microbiota with significant differences on days 16 and 22. Beta diversity analysis revealed that EO771 breast tumor cell injection and Paclitaxel chemotherapy altered the gut microbial communities in mice. Enrichment of potentially protective microbes was found in post-exercise microbiota groups. Tumors of mice colonized with post-exercise microbiota exhibited more favorable cytokine profiles, including decreased vascular endothelial growth factor (VEGF) levels. Beneficial microbial and molecular outcomes were augmented with prebiotic supplementation. Exercise and prebiotic fiber demonstrated adjuvant action, potentially via an enhanced anti-tumor immune response modulated by advantageous gut microbial shifts.}, }
@article {pmid35681546, year = {2022}, author = {Huang, C and Mei, Q and Lou, L and Huang, Z and Fu, Y and Fan, J and Wang, J and Yin, N and Zheng, Y and Lu, Y and Zeng, Y}, title = {Ulcerative Colitis in Response to Fecal Microbiota Transplantation via Modulation of Gut Microbiota and Th17/Treg Cell Balance.}, journal = {Cells}, volume = {11}, number = {11}, pages = {}, doi = {10.3390/cells11111851}, pmid = {35681546}, issn = {2073-4409}, support = {SHDC12017X09, SHDC2020CR2014A//Shanghai Hospital Development Center/ ; 20181813//Shanghai Jiao Tong University School of Medicine/ ; 81970555//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) may contribute to disease remission in ulcerative colitis (UC). We studied the microbiota change and its regulation on T cells after FMT.
METHODS: Patients with mild to moderately active UC were included to receive FMT. The intestinal histopathological changes and barrier function were evaluated. The fecal samples of donors and patients were analyzed by 16S rRNA gene-based microbiota analysis, and the colon Th17 and Treg cells were assessed.
RESULTS: Fifteen patients completed the 8-week-follow-up. A total of 10 patients (66.7%) were in the responders (RE) group and five in the non-responders (NR) group. The Nancy histological index and fecal calprotectin decreased (p < 0.001, p = 0.06, respectively) and Occludin and Claudin1 increased in the RE group. The abundance of Faecalibaterium increased significantly by 2.3-fold in the RE group at week 8 (p = 0.043), but it was suppressed in the NR group. Fecal calprotectin (r = -0.382, p = 0.003) and Nancy index (r = -0.497, p = 0.006) were correlated inversely with the abundance of Faecalibacterium, respectively. In the RE group the relative mRNA expression of RORγt decreased and Foxp3 increased. Significantly decreased CD4+ RORγt+ Th17 and increased CD4+ Foxp3+ Treg were also observed in the RE group. The relative abundance of Faecalibacterium correlated with CD4+ RORγt+ Th17 (r = -0.430, p = 0.018) and CD4+ Foxp3+ Treg (r = 0.571, p = 0.001).
CONCLUSIONS: The long-term Faecalibaterium colonization following FMT plays a crucial role in UC remission by alleviating intestinal inflammation. This anti-inflammatory effect of Faecalibacterium may be achieved by regulating the imbalance of Th17/Treg levels in UC.}, }
@article {pmid35680942, year = {2022}, author = {Hui, Y and Vestergaard, G and Deng, L and Kot, WP and Thymann, T and Brunse, A and Nielsen, DS}, title = {Donor-dependent fecal microbiota transplantation efficacy against necrotizing enterocolitis in preterm pigs.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {48}, pmid = {35680942}, issn = {2055-5008}, support = {8022-00188B//Det Frie Forskningsråd (Danish Council for Independent Research)/ ; 8022-00188B//Det Frie Forskningsråd (Danish Council for Independent Research)/ ; 201706350028//China Scholarship Council (CSC)/ ; }, abstract = {The development of necrotizing enterocolitis (NEC), a life-threatening inflammatory bowel disease affecting preterm infants, is connected with gut microbiota dysbiosis. Using preterm piglets as a model for preterm infants we recently showed that fecal microbiota transplantation (FMT) from healthy suckling piglet donors to newborn preterm piglets decreased the NEC risk. However, in a follow-up study using donor stool from piglets recruited from another farm, this finding could not be replicated. This allowed us to study donor-recipient microbiota dynamics in a controlled model system with a clear difference in NEC phenotype. Preterm piglets (n = 38) were randomly allocated to receive control saline (CON), or rectal FMT using either the ineffective (FMT1) or the effective donor stool (FMT2). All animals were followed for four days before necropsy and gut pathological evaluation. Donor and recipient colonic gut microbiota (GM) were analyzed by 16 S rRNA gene amplicon sequencing and shotgun metagenomics. As expected, only FMT2 recipients were protected against NEC. Both FMT groups had shifted GM composition relative to CON, but FMT2 recipients had a higher lactobacilli relative abundance compared to FMT1. Limosilactobacillus reuteri and Lactobacillus crispatus strains of FMT recipients showed high phylogenetic similarity with their respective donors, indicating engraftment. Moreover, the FMT2 group had a higher lactobacilli replication rate and harbored specific glycosaminoglycan-degrading Bacteroides. In conclusion, subtle species-level donor differences translate to major changes in engraftment dynamics and the ability to prevent NEC. This could have implications for proper donor selection in future FMT trials for NEC prevention.}, }
@article {pmid35680592, year = {2022}, author = {Tang, XW and Wu, DP}, title = {[How I treat gastrointestinal tract acute graft versus host disease with fecal microbiota transplantation].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {43}, number = {5}, pages = {365-369}, doi = {10.3760/cma.j.issn.0253-2727.2022.05.003}, pmid = {35680592}, issn = {0253-2727}, }
@article {pmid35533688, year = {2022}, author = {Joachim, A and Schwerd, T and Hölz, H and Sokollik, C and Konrad, LA and Jordan, A and Lanzersdorfer, R and Schmidt-Choudhury, A and Hünseler, C and Adam, R}, title = {[Fecal Microbiota Transfer (FMT) in Children and Adolescents - Review and statement by the GPGE microbiome working group].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {60}, number = {6}, pages = {963-969}, doi = {10.1055/a-1801-0284}, pmid = {35533688}, issn = {1439-7803}, mesh = {Adolescent ; Child ; *Clostridioides difficile ; *Clostridium Infections/complications ; Dysbiosis/complications ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; *Microbiota ; Treatment Outcome ; }, abstract = {The human microbiome and especially the gastrointestinal microbiota are associated with health and disease. Disturbance in the composition or function of fecal microbiota (dysbiosis) plays a role in the development of pediatric gastrointestinal diseases. Fecal microbiota transfer (FMT) is a special intervention, where microbiota are transferred from a healthy donor.In this review we describe the current state of knowledge for FMT in pediatric patients. There is satisfactory evidence concerning FMT in patients with recurrent C. difficile infection. For inflammatory bowel disease, few studies show a potential benefit.Adverse events occurred frequently in clinical studies, but were mostly mild and transient. There are hardly any data on long-term side effects of FMT, which are particularly significant for pediatrics. In practice, there is uncertainty as to which application route, dosage or frequency should be used. Legally, donor stool is considered a drug in German-speaking countries, for which no marketing authorization exists.In conclusion, knowledge about physiology, efficacy and side effects of FMT is insufficient and legal concerns complicate its implementation. More studies on this topic are needed urgently.}, }
@article {pmid35277453, year = {2022}, author = {Ting, NL and Lau, HC and Yu, J}, title = {Cancer pharmacomicrobiomics: targeting microbiota to optimise cancer therapy outcomes.}, journal = {Gut}, volume = {71}, number = {7}, pages = {1412-1425}, doi = {10.1136/gutjnl-2021-326264}, pmid = {35277453}, issn = {1468-3288}, mesh = {Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Humans ; Immunotherapy ; *Microbiota ; *Neoplasms ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {Despite the promising advances in novel cancer therapy such as immune checkpoint inhibitors (ICIs), limitations including therapeutic resistance and toxicity remain. In recent years, the relationship between gut microbiota and cancer has been extensively studied. Accumulating evidence reveals the role of microbiota in defining cancer therapeutic efficacy and toxicity. Unlike host genetics, microbiota can be easily modified via multiple strategies, including faecal microbiota transplantation (FMT), probiotics and antibiotics. Preclinical studies have identified the mechanisms on how microbes influence cancer treatment outcomes. Clinical trials have also demonstrated the potential of microbiota modulation in cancer treatments. Herein, we review the mechanistic insights of gut microbial interactions with chemotherapy and ICIs, particularly focusing on the interplay between gut bacteria and the pharmacokinetics (eg, metabolism, enzymatic degradation) or pharmacodynamics (eg, immunomodulation) of cancer treatment. The translational potential of basic findings in clinical settings is then explored, including using microbes as predictive biomarkers and microbial modulation by antibiotics, probiotics, prebiotics, dietary modulations and FMT. We further discuss the current limitations of gut microbiota modulation in patients with cancer and suggest essential directions for future study. In the era of personalised medicine, it is crucial to understand the microbiota and its interactions with cancer. Manipulating the gut microbiota to augment cancer therapeutic responses can provide new insights into cancer treatment.}, }
@article {pmid35672382, year = {2022}, author = {Bose, D and Chatterjee, S and Older, E and Seth, R and Janulewicz, P and Saha, P and Mondal, A and Carlson, JM and Decho, AW and Sullivan, K and Klimas, N and Lasley, S and Li, J and Chatterjee, S}, title = {Host gut resistome in Gulf War chronic multisymptom illness correlates with persistent inflammation.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {552}, pmid = {35672382}, issn = {2399-3642}, support = {W81XWH-13-2-0072//U.S. Department of Defense (United States Department of Defense)/ ; W81XWH1810374//U.S. Department of Defense (United States Department of Defense)/ ; OIA-1655740//NSF | BIO | Division of Biological Infrastructure (DBI)/ ; I01CX001923-01//U.S. Department of Veterans Affairs (Department of Veterans Affairs)/ ; }, abstract = {Chronic multisymptom illness (CMI) affects a subsection of elderly and war Veterans and is associated with systemic inflammation. Here, using a mouse model of CMI and a group of Gulf War (GW) Veterans' with CMI we show the presence of an altered host resistome. Results show that antibiotic resistance genes (ARGs) are significantly altered in the CMI group in both mice and GW Veterans when compared to control. Fecal samples from GW Veterans with persistent CMI show a significant increase of resistance to a wide class of antibiotics and exhibited an array of mobile genetic elements (MGEs) distinct from normal healthy controls. The altered resistome and gene signature is correlated with mouse serum IL-6 levels. Altered resistome in mice also is correlated strongly with intestinal inflammation, decreased synaptic plasticity, reversible with fecal microbiota transplant (FMT). The results reported might help in understanding the risks to treating hospital acquired infections in this population.}, }
@article {pmid35665355, year = {2022}, author = {Chen, Y and Zhiliang, L and Jiaqu, C and Xiaoqiong, L and Shaoyi, Z and Chunlian, M and Yinmei, Y and Bo, Y and Di, Z and Hongliang, T and Ning, L and Qiyi, C and Huanlong, Q}, title = {Fecal Microbiota and Human Intestinal Fluid Transplantation: Methodologies and Outlook.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {830004}, doi = {10.3389/fmed.2022.830004}, pmid = {35665355}, issn = {2296-858X}, abstract = {Fecal microbiota transplantation (FMT) is a therapy that involves the transplantation of healthy human fecal microorganisms into the gut of patients to rebuild or consolidate the intestinal microecology. It has been utilized in many diseases. However, FMT had a limited effect on patients with small intestinal diseases because of the unique ecological characteristics of the microorganisms. Thus, we proposed a new microecology transplantation therapy called human intestinal fluid transplantation (HIFT). Human intestinal fluid can be collected through a nasojejunal tube and be made into capsules using the freeze-dried powder method. In addition, strict standards for donor screening and management have been established. We are currently developing a high-standard HIFT preparation system and conducting high-quality clinical studies to validate the safety and efficacy of HIFT combined with FMT.}, }
@article {pmid35664229, year = {2022}, author = {Li, M and Yang, L and Mu, C and Sun, Y and Gu, Y and Chen, D and Liu, T and Cao, H}, title = {Gut microbial metabolome in inflammatory bowel disease: From association to therapeutic perspectives.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {2402-2414}, doi = {10.1016/j.csbj.2022.03.038}, pmid = {35664229}, issn = {2001-0370}, abstract = {Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a set of clinically chronic, relapsing gastrointestinal inflammatory disease and lacks of an absolute cure. Although the precise etiology is unknown, developments in high-throughput microbial genomic sequencing significantly illuminate the changes in the intestinal microbial structure and functions in patients with IBD. The application of microbial metabolomics suggests that the microbiota can influence IBD pathogenesis by producing metabolites, which are implicated as crucial mediators of host-microbial crosstalk. This review aims to elaborate the current knowledge of perturbations of the microbiome-metabolome interface in IBD with description of altered composition and metabolite profiles of gut microbiota. We emphasized and elaborated recent findings of several potentially protective metabolite classes in IBD, including fatty acids, amino acids and derivatives and bile acids. This article will facilitate a deeper understanding of the new therapeutic approach for IBD by applying metabolome-based adjunctive treatment.}, }
@article {pmid35664001, year = {2022}, author = {Liu, P and Zhou, X and Zhang, H and Wang, R and Wu, X and Jian, W and Li, W and Yuan, D and Wang, Q and Zhao, W}, title = {Danggui-Shaoyao-San Attenuates Cognitive Impairment via the Microbiota-Gut-Brain Axis With Regulation of Lipid Metabolism in Scopolamine-Induced Amnesia.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {796542}, doi = {10.3389/fimmu.2022.796542}, pmid = {35664001}, issn = {1664-3224}, abstract = {Danggui-Shaoyao-San (DSS) has a long history of being used as a traditional medicine (TCM) and has been reported to show therapeutic effects in alleviating the symptoms of cognitive impairment. The purpose of this study was to investigate whether DSS treatment attenuates cognitive impairment via the microbiota-gut-brain axis in scopolamine-induced amnesia. In this work, we first performed the Morris water maze (MWM) test and novel object recognition (NOR) test to evaluate the memory function of treated C57BL/6N mice. Then we evaluated 16S rRNA for gut microbiota analysis, as well as assessment of blood-brain barrier function and intestinal barrier function and lipid metabolism analysis on tissues from different groups. We hypothesised that DSS may affect brain function and behavior through the gut-brain axis in a bidirectional interplay with both top-down and bottom-up regulation. Furthermore, in order to confirm whether intestinal flora plays a crucial role in scopolamine-induced amnesia, C57BL/6N mice were treated with fecal microbial transplantation (FMT), and then behavioral tests were performed. The mice's feces were simultaneously evaluated by 16S rRNA analysis. The result supported that the FMT-induced improvement in cognitive function highlights the role of the gut microbiota-brain axis to mediate cognitive function and behavior. Besides theses works, more findings indicated that DSS altered lipid metabolism by activating LXR-PPAR-γ and repaired mucosal barrier dysfunction assessed with a broad range of techniques, which attenuated cognitive impairment via the microbiota-gut-brain axis.}, }
@article {pmid35662937, year = {2022}, author = {You, H and Tan, Y and Yu, D and Qiu, S and Bai, Y and He, J and Cao, H and Che, Q and Guo, J and Su, Z}, title = {The Therapeutic Effect of SCFA-Mediated Regulation of the Intestinal Environment on Obesity.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {886902}, doi = {10.3389/fnut.2022.886902}, pmid = {35662937}, issn = {2296-861X}, abstract = {Intestinal environment disorder is a potential pathological mechanism of obesity. There is increasing evidence that disorders in the homeostasis of the intestinal environment can affect various metabolic organs, such as fat and liver, and lead to metabolic diseases. However, there are few therapeutic approaches for obesity targeting the intestinal environment. In this review, on the one hand, we discuss how intestinal microbial metabolites SCFA regulate intestinal function to improve obesity and the possible mechanisms and pathways related to obesity-related pathological processes (depending on SCFA-related receptors such as GPCRs, MCT and SMCT, and through epigenetic processes). On the other hand, we discuss dietary management strategies to enrich SCFA-producing bacteria and target specific SCFA-producing bacteria and whether fecal bacteria transplantation therapy to restore the composition of the gut microbiota to regulate SCFA can help prevent or improve obesity. Finally, we believe that it will be of great significance to establish a working model of gut- SCFA- metabolic disease development in the future for the improvement this human health concern.}, }
@article {pmid35660350, year = {2022}, author = {Yan, S and Chang, J and Hao, X and Liu, J and Tan, X and Geng, Z and Wang, Z}, title = {Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {102}, number = {}, pages = {154217}, doi = {10.1016/j.phymed.2022.154217}, pmid = {35660350}, issn = {1618-095X}, abstract = {BACKGROUND: Colitis-associated cancer (CAC) is known to be a complex combination of tumor cells, non-tumor cells and a large intestinal flora. The increasing role of intestinal flora in CAC may represent a new approach to improving CAC treatment. Berberine can reduce colorectal adenoma recurrence and inhibit colorectal carcinogenesis.
PURPOSE: Berberine has demonstrated efficacy for the control and suppression of CAC. Given the low oral absorption into the blood and large intestinal excretion of berberine, intestinal flora may be one of the important targets of berberine inhibiting the occurrence of colorectal cancer (CRC). The purpose of this study was to investigate the effects of berberine on intestinal flora in CAC mice and its ability to remodel intestinal flora to improve short-chain fatty acid metabolism.
STUDY DESIGN AND METHODS: The CAC model in mice was induced by Azoxymethane/Dextran sodium sulfate (AOM/DSS). Berberine was administered daily at doses of 50 and 100 mg/kg, and aspirin was used as the positive control. The effect of berberine on colitis-associated colorectal tumorigenesis was assessed by general imaging, tumor counting, and Ki67 staining. Intestinal flora changes were detected by 16S rDNA sequencing technology. Targeted short-chain fatty acid detection was performed by GC-MS/MS, and Lipopolysaccharide (LPS) levels in feces were quantified with an ELISA kit. The signaling pathway of TLR4/NF-κB P65/IL-6/p-STAT3 was evaluated by Western blotting and immunofluorescence. The expression levels of intestinal barrier functional biomarkers Occludin and ZO-1 were detected by immunohistochemistry. Fecal flora transplantation (FMT) was used to evaluate the effect of intestinal flora in inhibiting inflammatory cancer transformation by berberine.
RESULTS: Berberine reduced the number and load of tumors in CAC mice. Berberine remodeled the composition of pathogenic and beneficial bacteria in mice with colitis-associated colorectal tumorigenesis. Berberine treatment resulted in increases in fecal butyric acid, acetic acid and propionic acid levels, but did not alter isobutyric acid, isovaleric acid, valeric acid and caproic acid. In addition, berberine reduced LPS content in feces in mice with colitis-associated colorectal tumorigenesis. Occludin and ZO-1 were upregulated, and the TLR4/p-NF-κB p65/IL-6/p-STAT3 inflammatory-cancer transformation pathway was inhibited with berberine. The FMT results further verified that the berberine-treated intestinal flora was sufficient to alleviate the occurrence of colonic tumors associated with colitis in mice.
CONCLUSION: Our study showed that berberine alleviated the colitis-associated colorectal tumorigenesis from three equilibrium levels: (1) Pathogenic and beneficial bacteria; (2) Short-chain fatty acids and LPS produced by intestinal flora; and (3) Inflammatory cancer transformation signaling and intestinal barrier function. This study provided a new approach and experimental basis for the application of berberine in the treatment of CAC in clinical practice.}, }
@article {pmid35658593, year = {2022}, author = {Fang, H and Fang, M and Wang, Y and Zhang, H and Li, J and Chen, J and Wu, Q and He, L and Xu, J and Deng, J and Liu, M and Deng, Y and Chen, C}, title = {Indole-3-Propionic Acid as a Potential Therapeutic Agent for Sepsis-Induced Gut Microbiota Disturbance.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0012522}, doi = {10.1128/spectrum.00125-22}, pmid = {35658593}, issn = {2165-0497}, abstract = {The effects of using gut microbiota metabolites instead of live microorganisms to modulate sepsis-induced gut dysbiosis remain largely unknown. We assessed the effects of microbiota metabolite indole-3-propionic acid (IPA) on gut microbiota in mice during sepsis. Sepsis models were constructed by cecal ligation and puncture (CLP) methods. Fecal microbiota composition analysis was performed to characterize the gut microbiota composition. Fecal microbiota transplantation was performed to validate the roles of gut microbiota on sepsis progression. IPA-treated mice exhibited lower serum inflammatory mediator levels and a higher survival rate than those of saline-treated mice after modeling of sepsis, which were negated in the presence of antibiotics. Compared with saline-treated mice after modeling, IPA-treated mice showed a markedly different intestinal microbiota composition, with an enrichment of Bifidobacteriaceae family and a depletion of Enterobacteriaceae family. Mice gavaged with postoperative feces from IPA-treated animals displayed better survival than mice gavaged with feces from saline-treated animals. Overall, these data suggest that IPA offers a microbe-modulated survival advantage in septic mice, indicating that some microbiota metabolites could replace live microorganisms as potential options for regulation of sepsis-induced gut dysbiosis. IMPORTANCE The role of gut microbiota in the pathophysiology of sepsis is gaining increasing attention and developing effective and safe sepsis therapies targeting intestinal microorganisms is promising. Given the safety of probiotic supplementation or fecal microbiota transplantation in critically ill patients, identifying an abiotic agent to regulate the intestinal microbiota of septic patients is of clinical significance. This study revealed that IPA, a microbiota-generated tryptophan metabolite, ameliorated sepsis-induced mortality and decreased the serum levels of proinflammatory cytokines by modulating intestinal microbiota. Although IPA did not increase the abundance and diversity of the microbiota of septic mice, it significantly decreased the number of Enterobacteriaceae family. These findings indicate that a specific microbiota metabolite (e.g., IPA) can mediate the intestinal microbiota apart from FMT or probiotics.}, }
@article {pmid35654347, year = {2022}, author = {Xu, L and Zhang, Q and Dou, X and Wang, Y and Wang, J and Zhou, Y and Liu, X and Li, J}, title = {Fecal microbiota transplantation from young donor mice improves ovarian function in aged mice.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jgg.2022.05.006}, pmid = {35654347}, issn = {1673-8527}, abstract = {Advanced maternal age is characterized by declines in the quantity and quality of oocytes in the ovaries, and the aging process is accompanied by changes in gut microbiota composition. However, little is known about the relationship between gut microbiota and ovarian aging. By using fecal microbiota transplantation (FMT) to transplant material from young (5-week-old) into aged (42-week-old) mice, we find that the composition of gut microbiota in FMT-treated mice presents a "younger-like phenotype" and an increase of commensal bacteria, such as Bifidobacterium and Ruminococcaceae. Moreover, the FMT-treated mice show increased anti-inflammatory cytokine IL-4 and decreased pro-inflammatory cytokine IFN-γ. Fertility tests for assessing ovarian function reveal that the first litter size of female FMT-treated mice is significantly higher than that of the non-FMT group. Morphology analysis demonstrates a dramatic decrease in follicle atresia and apoptosis as well as an increase in cellular proliferation in the ovaries of the FMT-treated mice. Our results also show that FMT improves the immune microenvironment in aged ovaries, with decreased macrophages and macrophage-derived multinucleated giant cells (MNGCs). These results suggest that FMT from young donors could be a good choice for delaying ovarian aging.}, }
@article {pmid35653887, year = {2022}, author = {Duan, S and Li, X and Fan, G and Liu, R}, title = {Targeting bile acid signaling for the treatment of liver diseases: From bench to bed.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {152}, number = {}, pages = {113154}, doi = {10.1016/j.biopha.2022.113154}, pmid = {35653887}, issn = {1950-6007}, abstract = {Liver diseases and related complications have become one of the leading causes of morbidity and mortality worldwide, yet effective medicine or approved treatment approach is still limited. Thus, novel therapy is urgently required to prevent or at least slow down the growing burden of liver transplantation or even death caused by malignant liver diseases. As the irreplaceable modulator of hepatic and intestinal signaling cascades, bile acids (BAs) play complex physiological as well as pathological roles in regulating energy and immune homeostasis in various liver diseases, including but not limited to metabolic diseases and cholangiopathies, making them highly attractive therapeutic targets. In the current review, recent progress in the research of enterohepatic circulation of BAs and potential therapeutic targets of BAs signaling, especially the development of currently available treatments, including agonizts of FXR and TGR5, analogs of FGF19, inhibitors of ASBT, and the regulation of gut microbiome through fecal microbiota transplantation were extensively summarized. Their protective effects, molecular mechanisms, and outcomes of clinical trials were highlighted. The structural features of these candidates and perspectives for their future development were further discussed. In conclusion, we believe that pharmacological therapies targeting BAs signaling represent promising and efficient strategies for the treatment of complex and multifactorial liver disorders.}, }
@article {pmid35650202, year = {2022}, author = {Pu, Y and Zhang, Q and Tang, Z and Lu, C and Wu, L and Zhong, Y and Chen, Y and Hashimoto, K and Luo, Y and Liu, Y}, title = {Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation.}, journal = {Translational psychiatry}, volume = {12}, number = {1}, pages = {223}, pmid = {35650202}, issn = {2158-3188}, support = {21H00184//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05612//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 82101616//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81973540//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Depression is common in patients with rheumatoid arthritis (RA); however, the precise mechanisms underlying a link between depression and RA remain unclear. Accumulating evidence suggests the role of gut-microbiota-brain axis in depression. In this study, we investigated whether collagen-induced arthritis (CIA) mice produce depression-like behaviors and abnormal composition of gut microbiota. Furthermore, we investigated whether fecal microbiota transplantation (FMT) from RA patients causes depression-like phenotypes in antibiotic cocktail (ABX)-treated mice. CIA mice displayed depression-like behaviors, increased blood levels of pro-inflammatory cytokine interleukin-6 (IL-6), decreased expression of synaptic proteins in the prefrontal cortex (PFC), and abnormal composition of gut microbiota. Furthermore, FMT from RA patients caused depression-like phenotypes, alterations of gut microbiota composition, increased levels of IL-6 and tumor necrosis factor-α (TNF-α), and downregulation of synaptic proteins in the PFC compared to FMT from healthy controls. There were correlations between relative abundance of microbiota and plasma cytokines, expression of synaptic proteins in the PFC or depression-like behaviors. Interestingly, FMT from RA patients induced T cells differentiation in Peyer's patches and spleen. Reduced percentage of Treg cells with an increase of Th1/Th2 index was observed in the mice after FMT from RA patients. These findings suggest that CIA mice exhibit depression-like behaviors, systemic inflammation, and abnormal composition of gut microbiota, and that FMT from RA patients produces depression-like behaviors in ABX-treated mice via T cells differentiation. Therefore, abnormalities in gut microbiota in RA patients may contribute to depression via gut-microbiota-brain axis.}, }
@article {pmid35647000, year = {2022}, author = {Zhi, W and Song, W and Abdi Saed, Y and Wang, Y and Li, Y}, title = {Fecal Capsule as a Therapeutic Strategy in IgA Nephropathy: A Brief Report.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {914250}, doi = {10.3389/fmed.2022.914250}, pmid = {35647000}, issn = {2296-858X}, abstract = {In this brief report, we reported an IgA nephropathy (IgAN) patient who presented in November 2020 with an acute exacerbation with massive proteinuria and diarrhea. He had the earliest onset in 2018 when his IgAN was diagnosed by renal biopsy. He has been treated with active ACEI/ARB drugs for more than 90 days, intermittent steroid therapy, combined with anti-infective therapy. Although his acute symptoms resolved with each episode, he became increasingly severe as the interval between episodes shortened. Accordingly, the immunosuppressive drugs were administered under the KDIGO guidelines and related guidelines. However, the patient and his family refused this treatment. We pondered over the possible pathogenesis of IgAN, and after a full discussion with the patient and his family, FMT was administered to him after obtaining his informed consent. During the FMT procedure, one healthy volunteer (the doctor himself) also took the FMT capsules. In the end, the patient's urine protein dropped significantly and even turned negative after treatment. Neither the patient nor the healthy volunteer experienced any serious adverse effects during the use of the capsules and the subsequent 6-month follow-up period. We also used metagenomic sequencing to analyze the intestinal flora of patients before and after treatment, and a gradual increase stood out in the abundance of the patient's intestinal flora after drug administration.}, }
@article {pmid35646285, year = {2022}, author = {Said, I and Ahad, H and Said, A}, title = {Gut microbiome in non-alcoholic fatty liver disease associated hepatocellular carcinoma: Current knowledge and potential for therapeutics.}, journal = {World journal of gastrointestinal oncology}, volume = {14}, number = {5}, pages = {947-958}, doi = {10.4251/wjgo.v14.i5.947}, pmid = {35646285}, issn = {1948-5204}, abstract = {Metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). The gut microbiome is closely connected to the liver via the portal vein, and has recently been identified as a predictor of liver disease state. Studies in NAFLD, cirrhosis and HCC have identified certain microbial signatures associated with these diseases, with the disease-associated microbiome changes collectively referred to as dysbiosis. The pathophysiologic underpinnings of these observations are an area of ongoing investigation, with current evidence demonstrating that the gut microbiome can influence liver disease and carcinogenesis via effects on intestinal permeability (leaky gut) and activation of the innate immune system. In the innate immune system, pathogen recognition receptors (Toll like receptors) on resident liver cells and macrophages cause liver inflammation, fibrosis, hepatocyte proliferation and reduced antitumor immunity, leading to chronic liver disease and carcinogenesis. Dysbiosis-associated changes include increase in secondary bile acids and reduced expression of FXR (nuclear receptor), which have also been associated with deleterious effects on lipid and carbohydrate metabolism associated with progressive liver disease. Longitudinal experimental and clinical studies are needed in different populations to examine these questions further. The role of therapeutics that modulate the microbiome is an emerging field with experimental studies showing the potential of diet, probiotics, fecal microbiota transplantation and prebiotics in improving liver disease in experimental models. Clinical studies are ongoing with preliminary evidence showing improvement in liver enzymes and steatosis. The microbial profile is different in responders to cancer immunotherapy including liver cancer, but whether or not manipulation of the microbiome can be utilized to affect response is being investigated.}, }
@article {pmid35646276, year = {2022}, author = {Hoilat, GJ and Suhail, FK and Adhami, T and John, S}, title = {Evidence-based approach to management of hepatic encephalopathy in adults.}, journal = {World journal of hepatology}, volume = {14}, number = {4}, pages = {670-681}, doi = {10.4254/wjh.v14.i4.670}, pmid = {35646276}, issn = {1948-5182}, abstract = {Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function and represents one of the many complications of portal hypertension and decompensated liver disease. Although ammonia is clearly implicated in the pathogenesis of HE, the pathogenesis of HE is multifactorial with numerous mechanisms that results in functional impairment of neuronal cells. The initial management of HE focuses on supportive care and stabilization which includes providing appropriate nutritional support. Thereafter, focus should be on identifying and treating the precipitating factors. There are many therapeutic agents available for the management of HE, most of which are directed towards lowering the gut nitrogen load and thus the serum ammonia level. This review aims to provide an update on the conventional and emerging treatment options for HE.}, }
@article {pmid35643532, year = {2022}, author = {He, Z and Ma, Y and Yang, S and Zhang, S and Liu, S and Xiao, J and Wang, Y and Wang, W and Yang, H and Li, S and Cao, Z}, title = {Gut microbiota-derived ursodeoxycholic acid from neonatal dairy calves improves intestinal homeostasis and colitis to attenuate extended-spectrum β-lactamase-producing enteroaggregative Escherichia coli infection.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {79}, pmid = {35643532}, issn = {2049-2618}, support = {2021YFF1000703-03//National Key Research and Development Program of China/ ; }, abstract = {BACKGROUND: Antimicrobials are often used to prevent and treat diarrhea induced by enteroaggregative Escherichia coli (EAEC) in young ruminants. However, drug overuse or misuse accelerates the spread of multidrug-resistant extended-spectrum β-lactamase (ESBL)-producing E. coli. Thus, supplementary foods as alternatives to antibiotics are needed to prevent colibacillus diarrhea in neonatal dairy calves. Ursodeoxycholic acid (UDCA), a therapeutic bile acid, helps alleviate colitis. However, how UDCA helps alleviate ESBL-EAEC-induced clinical symptoms and colitis remains unclear.
RESULTS: We investigated the microbial profiles and metabolites of healthy and diarrheic neonatal calves to determine microbial and metabolite biomarkers in early-life development. Both the gut microbiota communities and their associated metabolites differed between healthy and diarrheic calves. Commensal Butyricicoccus, Faecalibacterium, Ruminococcus, Collinsella, and Coriobacterium were key microbial markers that distinguished healthy and diarrheic gut microbiomes. Random forest machine-learning algorithm and Spearman correlation results indicated that enriched UDCA, short-chain fatty acids (SCFAs), and other prebiotics were strongly positively correlated with these five bacterial genera. We explored the effect of ursodiol on bacterial growth, cell adherence, and lipopolysaccharide-treated Caco-2 cells. Adding ursodiol induced direct antibacterial effects, suppressed proinflammatory effects, and reduced cell integrity damage. Oral ursodiol delivery to neonatal mice exhibited significant antibacterial effects and helped maintain colonic barrier integrity in mouse models of peritonitis sepsis and oral infection. UDCA supplementation attenuated colitis and recovered colonic SCFA production. To validate this, we performed fecal microbiota transplantations to inoculate ESBL-EAEC-infected neonatal mice. Microbiotas from UDCA-treated neonatal mice ameliorated colitis and hindgut commensal bacterial damage compared with that of the microbiotas from the control and placebo mice, as evidenced by colonization of abundant bacteria, including Oscillospiraceae, Ruminococcaceae, Lachnospiraceae, and Clostridia_UCG-014, and upregulated SCFA production.
CONCLUSIONS: This study provided the first evidence that UDCA could confer diarrhea resistance in ESBL-EAEC-infected newborn dairy calves. UDCA blocked bacterial growth and invasion both in vitro and in vivo, alleviated commensal bacterial dysbiosis during ESBL-EAEC infection in neonatal mouse models of sepsis and colitis via the TGR5-NF-κB axis, and upregulated SCFA production in the hindgut digesta. Our findings provide insight into the UDCA-mediated remission of ESBL-EAEC infections and the potential role of UDCA as an antibiotic alternative. Video abstract.}, }
@article {pmid35642928, year = {2022}, author = {Liu, Q and Zuo, T and Lu, W and Yeoh, YK and Su, Q and Xu, Z and Tang, W and Yang, K and Zhang, F and Lau, LHS and Lui, RNS and Chin, ML and Wong, R and Cheung, CP and Zhu, W and Chan, PKS and Chan, FKL and Lui, GC and Ng, SC}, title = {Longitudinal Evaluation of Gut Bacteriomes and Viromes after Fecal Microbiota Transplantation for Eradication of Carbapenem-Resistant Enterobacteriaceae.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0151021}, doi = {10.1128/msystems.01510-21}, pmid = {35642928}, issn = {2379-5077}, abstract = {Understanding the role of fecal microbiota transplantation (FMT) in the decolonization of multidrug-resistant organisms (MDRO) is critical. Specifically, little is known about virome changes in MDRO-infected subjects treated with FMT. Using shotgun metagenomic sequencing, we characterized longitudinal dynamics of the gut virome and bacteriome in three recipients who successfully decolonized carbapenem-resistant Enterobacteriaceae (CRE), including Klebsiella spp. and Escherichia coli, after FMT. We observed large shifts of the fecal bacterial microbiota resembling a donor-like community after transfer of a fecal microbiota dominated by the genus Ruminococcus. We found a substantial expansion of Klebsiella phages after FMT with a concordant decrease of Klebsiella spp. and striking increase of Escherichia phages in CRE E. coli carriers after FMT. We also observed the CRE elimination and similar evolution of Klebsiella phage in mice, which may play a role in the collapse of the Klebsiella population after FMT. In summary, our pilot study documented bacteriome and virome alterations after FMT which mediate many of the effects of FMT on the gut microbiome community. IMPORTANCE Fecal microbiota transplantation (FMT) is an effective treatment for multidrug-resistant organisms; however, introducing a complex mixture of microbes also has unknown consequences for landscape features of gut microbiome. We sought to understand bacteriome and virome alterations in patients undergoing FMT to treat infection with carbapenem-resistant Enterobacteriaceae. This finding indicates that transkingdom interactions between the virome and bacteriome communities may have evolved in part to support efficient FMT for treating CRE.}, }
@article {pmid35642838, year = {2022}, author = {Fang, H and Wang, Y and Deng, J and Zhang, H and Wu, Q and He, L and Xu, J and Shao, X and Ouyang, X and He, Z and Zhou, Q and Wang, H and Deng, Y and Chen, C}, title = {Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0139921}, doi = {10.1128/msystems.01399-21}, pmid = {35642838}, issn = {2379-5077}, abstract = {Sepsis-associated encephalopathy (SAE) is common in septic patients and is associated with adverse outcomes. The gut microbiota has been recognized as a key mediator of neurological disease development. However, the exact role of the gut microbiota in regulating SAE remains elusive. Here, we investigated the role of the gut microbiota in SAE and its underlying mechanisms. Cecal ligation and puncture (CLP) was conducted to induce sepsis in mice. Neurological scores were recorded to distinguish SAE-resistant (SER) (score of >6 at 36 h postoperatively) from SAE-susceptible (SES) (score of ≤6 at 36 h postoperatively) mice. 16S rRNA gene sequencing and metabolomics analyses were used to characterize the gut microbiota in the two groups. Fecal microbiota transplantation was performed to validate the role of the gut microbiota in SAE progression. The gut microbiota was more severely disrupted in SES mice than in SER mice after sepsis modeling. Interestingly, mice receiving postoperative feces from SES mice exhibited more severe cortical inflammation than mice receiving feces from SER mice. Indole-3-propionic acid (IPA), a neuroprotective molecule, was more enriched in feces from SER mice than in feces from SES mice. IPA alleviated CLP-induced anxiety and spatial memory impairment in septic mice. Moreover, IPA markedly inhibited NLRP3 inflammasome activation and interleukin-1β (IL-1β) secretion in lipopolysaccharide-stimulated microglia. These responses were attenuated after antagonizing the aryl hydrocarbon receptor. Our study indicates that the variability in sepsis-induced gut dysbiosis mediates the differential susceptibility to SAE in CLP-induced experimental sepsis mice, and microbially derived IPA is possibly involved in SAE development as a neuroprotective compound. IMPORTANCE The bidirectional interactions between the gut microbiota and sepsis-associated encephalopathy (SAE) are not well characterized. We found that the gut microbiota was more severely disturbed in SAE-susceptible (SES) mice than in SAE-resistant (SER) mice after sepsis modeling. Mice gavaged with postoperative feces from SES mice exhibited more severe neuroinflammation than mice gavaged with feces from SER mice. The gut microbiota from SER mice enriched a neuroprotective metabolite, IPA, which appeared to protect mice from SAE. The potential underlying mechanism of the protective effect of IPA may be mediated via the inhibition of NLRP3 inflammasome activation and IL-1β secretion in microglia. These anti-inflammatory effects of IPA may be regulated by aryl hydrocarbon receptors. These results enhance our understanding of the role of the intestinal microbiota in sepsis. In particular, gut microbiota-derived IPA may serve as a potential therapeutic agent to prevent neuroinflammation in SAE.}, }
@article {pmid35635005, year = {2022}, author = {Li, WJ and Zhang, L and Wu, HX and Li, M and Wang, T and Zhang, WB and Du, ZY and Zhang, ML}, title = {Intestinal Microbiota Mediates Gossypol-Induced Intestinal Inflammation, Oxidative Stress, and Apoptosis in Fish.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c01263}, pmid = {35635005}, issn = {1520-5118}, abstract = {Gossypol, the main antinutritional factor in cottonseed protein concentrate (CPC), could affect the growth conditions of fish, but the underlying mechanism remains unclear. In this study, an 8-week feeding trial was carried out to investigate the effects of gossypol on Nile tilapia (Oreochromis niloticus). Three experimental diets were designed, including control diet (CON), control diet supplemented with 150 mg/kg gossypol (ML), and 300 mg/kg gossypol (MH). 16S rRNA gene sequencing showed that gossypol significantly reduced the richness and diversity of the gut microbiota. Untargeted metabolite analysis revealed that most metabolites were down-regulated by gossypol, and riboflavin was the key metabolite with significant difference between CON-treated and gossypol-treated groups. Gossypol caused intestinal inflammation, oxidative stress, and apoptosis. Through fecal bacteria transplantation experiments, we demonstrated that intestinal microbiota mediated gossypol-induced negative effects, suggesting that intestinal microbiota and its metabolite may account for the harmful effects of gossypol.}, }
@article {pmid35634716, year = {2022}, author = {González-Dávila, P and Schwalbe, M and Danewalia, A and Wardenaar, R and Dalile, B and Verbeke, K and Mahata, SK and El Aidy, S}, title = {Gut microbiota transplantation drives the adoptive transfer of colonic genotype-phenotype characteristics between mice lacking catestatin and their wild type counterparts.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2081476}, doi = {10.1080/19490976.2022.2081476}, pmid = {35634716}, issn = {1949-0984}, abstract = {The gut microbiota is in continuous interaction with the intestinal mucosa via metabolic, neuro-immunological, and neuroendocrine pathways. Disruption in levels of antimicrobial peptides produced by the enteroendocrine cells, such as catestatin, has been associated with changes in the gut microbiota and imbalance in intestinal homeostasis. However, whether the changes in the gut microbiota have a causational role in intestinal dyshomeostasis has remained elusive. To this end, we performed reciprocal fecal microbial transplantation in wild-type mice and mice with a knockout in the catestatin coding region of the chromogranin-A gene (CST-KO mice). Combined microbiota phylogenetic profiling, RNA sequencing, and transmission electron microscopy were employed. Fecal microbiota transplantation from mice deficient in catestatin (CST-KO) to microbiota-depleted wild-type mice induced transcriptional and physiological features characteristic of a distorted colon in the recipient animals, including impairment in tight junctions, as well as an increased collagen area fraction indicating colonic fibrosis. In contrast, fecal microbiota transplantation from wild-type mice to microbiota-depleted CST-KO mice reduced collagen fibrotic area, restored disrupted tight junction morphology, and altered fatty acid metabolism in recipient CST-KO mice. This study provides a comprehensive overview of the murine metabolic- and immune-related cellular pathways and processes that are co-mediated by the fecal microbiota transplantation and supports a prominent role for the gut microbiota in the colonic distortion associated with the lack of catestatin in mice. Overall, the data show that the gut microbiota may play a causal role in the development of features of intestinal inflammation and metabolic disorders, known to be associated with altered levels of catestatin and may, thus, provide a tractable target in the treatment and prevention of these disorders.}, }
@article {pmid35634319, year = {2022}, author = {Xia, Y and Shi, H and Qian, C and Han, H and Lu, K and Tao, R and Gu, R and Zhao, Y and Wei, Z and Lu, Y}, title = {Modulation of Gut Microbiota by Magnesium Isoglycyrrhizinate Mediates Enhancement of Intestinal Barrier Function and Amelioration of Methotrexate-Induced Liver Injury.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {874878}, doi = {10.3389/fimmu.2022.874878}, pmid = {35634319}, issn = {1664-3224}, abstract = {Background: The gut-liver axis plays a crucial role in various liver diseases. Therefore, targeting this crosstalk may provide a new treatment strategy for liver diseases. However, the exact mechanism underlying this crosstalk and its impact on drug-induced liver injury (DILI) requires clarification.
Aim: This study aimed to investigate the potential mechanism and therapeutic effect of MgIG on MTX-induced liver injury, which is associated with the gut-liver axis and gut microbiota.
Methods: An MTX-induced liver injury model was generated after 20-mg/kg/3d MTX application for 30 days. Meanwhile, the treatment group was treated with 40-mg/kg MgIG daily. Histological examination, aminotransferase, and aspartate aminotransferase enzyme levels were estimated to evaluate liver function. Immune cells infiltration and inflammatory cytokines were detected to indicate inflammation levels. Colon histological score, intestinal barrier leakage, and expression of tight junctions were employed to assess the intestinal injury. Bacterial translocation was observed using fluorescent in situ hybridisation, colony-forming unit counting, and lipopolysaccharide detection. Alterations in gut microbial composition were analysed using 16s rDNA sequencing and relative quantitative polymerase chain reaction. Short-chain-fatty-acids and lactic acid concentrations were then utilized to validate changes in metabolites of specific bacteria. Lactobacillus sp. supplement and fecal microbiota transplantation were used to evaluate gut microbiota contribution.
Results: MTX-induced intestinal and liver injuries were significantly alleviated using MgIG treatment. Bacterial translocation resulting from the intestinal barrier disruption was considered a crucial cause of MTX-induced liver injury and the therapeutic target of MgIG. Moreover, MgIG was speculated to have changed the gut microbial composition by up-regulating probiotic Lactobacillus and down-regulating Muribaculaceae, thereby remodelling the intestinal barrier and inhibiting bacterial translocation.
Conclusion: The MTX-induced intestinal barrier was protected owing to MgIG administration, which reshaped the gut microbial composition and inhibited bacterial translocation into the liver, thus attenuating MTX-related DILI.}, }
@article {pmid35631220, year = {2022}, author = {Yoo, JW and Shin, YJ and Ma, X and Son, YH and Jang, HM and Lee, CK and Kim, DH}, title = {The Alleviation of Gut Microbiota-Induced Depression and Colitis in Mice by Anti-Inflammatory Probiotics NK151, NK173, and NK175.}, journal = {Nutrients}, volume = {14}, number = {10}, pages = {}, doi = {10.3390/nu14102080}, pmid = {35631220}, issn = {2072-6643}, support = {2017R1A5A2014768//National Research Foundation of Korea/ ; }, abstract = {Gut microbiota dysbiosis is strongly associated with psychiatric disorders and inflammatory bowel disease (IBD). Herein, we examined whether the fecal microbiota of IBD patients with depression (IBDD) and their gut microbiota culture (iGm) could cause depression and colitis in mice and anti-inflammatory probiotics could mitigate depression in iGm-transplanted or immobilization stress (IS)-exposed mice. Fecal microbiota transplantation (FMT) from IBDD patients, which exhibited Enterobacteriaceae-rich gut microbiota, and its gut microbiota culture (iGm) increased depression-like behaviors in mice. Their treatments heightened the blood lipopolysaccharide (LPS) level and colonic IL-1β and IL-6 expression. However, FMT from healthy volunteers or sulfasalazine treatment alleviated cGm-induced depressive-like behaviors and hippocampal and colonic inflammation in mice. Moreover, oral administration of Lactobacillus plantarum NK151, Bifidobacterium longum NK173, and Bifidobacterium bifidum NK175, which inhibited LPS-induced IL-6 expression in macrophages, alleviated cGm-induced depression-like behaviors, hippocampal NF-κB+Iba1+ cell numbers and IL-1β and IL-6 expression, blood LPS, IL-6, and creatinine levels, and colonic NF-κB+CD11c+ number and IL-1β and IL-6 expression in mice. Treatment with NK151, NK173, or NK175 mitigated immobilization stress (IS)-induced depressive-like behaviors, neuroinflammation, and gut inflammation in mice. NK151, NK173, or NK175 also decreased IS-induced blood LPS, IL-6, and creatinine levels. The transplantation of Enterobacteriaceae-rich gut microbiota can cause depression and colitis, as IS exposure, and anti-inflammatory NK151, NK173, and NK175, may alleviate stress-induced fatigue, depression, and colitis by regulating the expression of proinflammatory and anti-inflammatory cytokines through the suppression of gut bacterial LPS.}, }
@article {pmid35631150, year = {2022}, author = {Wang, P and Ma, Y and Wang, D and Zhao, W and Hu, X and Chen, F and Zhao, X}, title = {Protective Effects of Dietary Resveratrol against Chronic Low-Grade Inflammation Mediated through the Gut Microbiota in High-Fat Diet Mice.}, journal = {Nutrients}, volume = {14}, number = {10}, pages = {}, doi = {10.3390/nu14101994}, pmid = {35631150}, issn = {2072-6643}, support = {32101959//National Natural Science Foundation of China/ ; 202244/WT_/Wellcome Trust/United Kingdom ; KJCX201915//the Collaborative Innovation Center of Beijing Academy of Agricultural and Forestry Sciences/ ; KJCX20200208//Scientific and Technological Innovation Ability Foundation of Beijing Academy of Agricultural and Forestry Sciences/ ; CARS-23//China Agriculture Research System of MOF and MRAR/ ; }, abstract = {Resveratrol (RSV), a natural polyphenol, has been shown to exert activity against obesity and related chronic inflammation. However, due to the poor bioavailability of RSV, the mechanisms of RSV against inflammation in obesity models remain unclear. In this study, we aimed to investigate the relationship between the gut bacteria and the anti-inflammation effects of RSV in HFD-fed mice. We found that RSV supplementation reduced fat accumulation and improved systemic inflammation in HFD-fed mice. Meanwhile, RSV attenuated HFD-induced changes in the gut microbiota's structure, which were associated with inflammatory parameters. A fecal microbiota transplantation (FMT) experiment proved that the anti-inflammation effects of RSV largely rely on the gut microbiota. Moreover, the microbiota-genera-changing trend in the FMT experiment was similar to that in the oral RSV-feeding experiment. Thus, these results demonstrate that modulation of the gut bacteria induced by RSV treatment has a therapeutic effect on chronic low-grade inflammation in HFD-fed mice.}, }
@article {pmid35630496, year = {2022}, author = {Gan, L and Bo, T and Liu, W and Wang, D}, title = {The Gut Microbiota May Affect Personality in Mongolian Gerbils.}, journal = {Microorganisms}, volume = {10}, number = {5}, pages = {}, doi = {10.3390/microorganisms10051054}, pmid = {35630496}, issn = {2076-2607}, support = {31872232//National Natural Science Foundation of China/ ; 32090024//State Natural Sciences Foundation Monumental Projects/ ; XDPB16//Strategic Priority Research Program of Chinese Academy of Sciences/ ; 2021M693158//Postdoctoral Research Foundation of China/ ; }, abstract = {The "gut-microbiota-brain axis" reveals that gut microbiota plays a critical role in the orchestrating behavior of the host. However, the correlation between the host personalities and the gut microbiota is still rarely known. To investigate whether the gut microbiota of Mongolian gerbils (Meriones unguiculatus) differs between bold and shy personalities, we compared the gut microbiota of bold and shy gerbils, and then we transplanted the gut microbiota of bold and shy gerbils into middle group gerbils (individuals with less bold and shy personalities). We found a significant overall correlation between host boldness and gut microbiota. Even though there were no significant differences in alpha diversity and beta diversity of gut microbiota between bold and shy gerbils, the Firmicutes/Bacteroidetes phyla and Odoribacter and Blautia genus were higher in bold gerbils, and Escherichia_shigella genus was lower. Furthermore, the fecal microbiota transplantation showed that changes in gut microbiota could not evidently cause the increase or decrease in the gerbil's boldness score, but it increased the part of boldness behaviors by gavaging the "bold fecal microbiota". Overall, these data demonstrated that gut microbiota were significantly correlated with the personalities of the hosts, and alteration of microbiota could alter host boldness to a certain extent.}, }
@article {pmid35630347, year = {2022}, author = {Shang, L and Tu, J and Dai, Z and Zeng, X and Qiao, S}, title = {Microbiota Transplantation in an Antibiotic-Induced Bacterial Depletion Mouse Model: Reproducible Establishment, Analysis, and Application.}, journal = {Microorganisms}, volume = {10}, number = {5}, pages = {}, doi = {10.3390/microorganisms10050902}, pmid = {35630347}, issn = {2076-2607}, support = {32030105//National Key Research and Development Program of China/ ; cstc2019ngzx0019//Chongqing Rongchang Agricultural and Animal Husbandry High-tech Industry Research and Development Project/ ; }, abstract = {The fecal bacteria transplantation (FMT) technique is indispensable when exploring the pathogenesis and potential treatments for microbiota-related diseases. For FMT clinical treatments, there are already systematic guidelines for donor selection, fecal bacterial separation, FMT frequency, and infusion methods. However, only a few studies have demonstrated the use of standardized FMT procedures for animal models used in theoretical research, creating difficulties for many new researchers in this field. In the present paper, we provide a brief overview of FMT and discuss its contribution to the current understanding of disease mechanisms that relate to microbiota. This protocol can be used to generate a commonly used FMT mouse model and provides a literature reference of customizable steps.}, }
@article {pmid35625513, year = {2022}, author = {Ugrayová, S and Švec, P and Hric, I and Šardzíková, S and Kubáňová, L and Penesová, A and Adamčáková, J and Pačesová, P and Horáková, J and Kolenová, A and Šoltys, K and Kolisek, M and Bielik, V}, title = {Gut Microbiome Suffers from Hematopoietic Stem Cell Transplantation in Childhood and Its Characteristics Are Positively Associated with Intra-Hospital Physical Exercise.}, journal = {Biology}, volume = {11}, number = {5}, pages = {}, doi = {10.3390/biology11050785}, pmid = {35625513}, issn = {2079-7737}, support = {APVV-17-0099//Slovak Research and Development Agency/ ; APVV-19-0222//Slovak Research and Development Agency/ ; No. MAGDG2000059//Grant program for the development of sport and education in the capital of the Slovak Republic in Bratislava/ ; UK/38/20//Comenius University/ ; UK/112/2021//Comenius University/ ; VEGA 1/0260/21//Vedecká grantová agentúra MŠVVaŠ SR a SAV (VEGA)/ ; }, abstract = {Gut microbiome impairment is a serious side effect of cancer treatment. The aim of this study was to identify the effects of hematopoietic stem cell transplantation (HSCT) treatment on gut microbiota composition in children with acute lymphoblastic leukemia (ALL). Fecal microbiotas were categorized using specific primers targeting the V1-V3 region of 16S rDNA in eligible pediatric ALL patients after HSCT (n = 16) and in healthy controls (Ctrl, n = 13). An intra-hospital exercise program was also organized for child patients during HSCT treatment. Significant differences in gut microbiota composition were observed between ALL HSCT and Ctrl with further negative effects. Plasma C-reactive protein correlated positively with the pathogenic bacteria Enterococcus spp. and negatively with beneficial bacteria Butyriccocus spp. or Akkermansia spp., respectively (rs = 0.511, p = 0.05; rs = -0.541, p = 0.04; rs = -0.738, p = 0.02). Bacterial alpha diversity correlated with the exercise training characteristics. Therefore, specific changes in the microbiota of children were associated with systemic inflammation or the ability to exercise physically during HSCT treatment.}, }
@article {pmid35625485, year = {2022}, author = {Dey, P and Ray Chaudhuri, S}, title = {Cancer-Associated Microbiota: From Mechanisms of Disease Causation to Microbiota-Centric Anti-Cancer Approaches.}, journal = {Biology}, volume = {11}, number = {5}, pages = {}, doi = {10.3390/biology11050757}, pmid = {35625485}, issn = {2079-7737}, support = {SRG/2021/000082//Science and Engineering Research Board/ ; }, abstract = {Helicobacter pylori infection is the only well-established bacterial cause of cancer. However, due to the integral role of tissue-resident commensals in maintaining tissue-specific immunometabolic homeostasis, accumulated evidence suggests that an imbalance of tissue-resident microbiota that are otherwise considered as commensals, can also promote various types of cancers. Therefore, the present review discusses compelling evidence linking tissue-resident microbiota (especially gut bacteria) with cancer initiation and progression. Experimental evidence supporting the cancer-causing role of gut commensal through the modulation of host-specific processes (e.g., bile acid metabolism, hormonal effects) or by direct DNA damage and toxicity has been discussed. The opportunistic role of commensal through pathoadaptive mutation and overcoming colonization resistance is discussed, and how chronic inflammation triggered by microbiota could be an intermediate in cancer-causing infections has been discussed. Finally, we discuss microbiota-centric strategies, including fecal microbiota transplantation, proven to be beneficial in preventing and treating cancers. Collectively, this review provides a comprehensive understanding of the role of tissue-resident microbiota, their cancer-promoting potentials, and how beneficial bacteria can be used against cancers.}, }
@article {pmid35624084, year = {2022}, author = {Jee, JJ and Lim, J and Park, S and Koh, H and Lee, HW}, title = {The gut microbial community differentially characterizes patients with nonalcoholic fatty liver disease.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15903}, pmid = {35624084}, issn = {1440-1746}, abstract = {BACKGROUND AND AIM: Discordant reports of the signature gut microbes involved in nonalcoholic fatty liver disease (NAFLD) have hampered understanding of the pathogenesis of the disease, and thus its diagnosis. Thus, we investigated diagnostic factors and the potential mechanisms for heterogenous NAFLD based on the gut environment, including microbes and functional pathways.
METHODS: Stools from 16 biopsy-proven NAFLD patients were analyzed for bacterial taxonomy and functional pathways based on 16s rRNA gene sequencing. Data from the physical examination, serum biochemistry, and the gut environment were subjected to a decision tree classifier to identify diagnostic markers.
RESULTS: We identified two NAFLD subpopulations: those with and without a gut microbiota similar to health controls (HCs), defined as PHC-like and P patients, respectively. Stools of PHC-like patients were significantly populated with Enterobacteriaceae and were inferred to be rich in metabolites degraded from dicarboxylic acid sugars. Significant colonization of Prevotella was observed in the stools of P patients, in parallel with enrichment of metabolites from heme b biosynthesis and sulfate reduction. As a potential mechanism, we suggest that protoporphyrin IX and/or protoheme from Prevotella participates in hepatic injury, and that endogenous hydrogen sulfide increases serum IL-6 level in P patients. However, endotoxin-producing Enterobacteriaceae are thought to produce glycerate, triggering a peroxisome proliferator- activated receptor-alpha-mediated decrease in IL-6 level and fat accumulation in PHC-like patients.
CONCLUSIONS: Heterogenous NAFLD subpopulations were identified, defined according to gut microbial composition and their potential underlying pathogenic mechanisms; our results raise the possibility of personalized treatment for NALFD patients.}, }
@article {pmid35623598, year = {2022}, author = {Pane, K and Boccella, S and Guida, F and Franzese, M and Maione, S and Salvatore, M}, title = {Role of gut microbiota in neuropathy and neuropathic pain states: A systematic preclinical review.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {105773}, doi = {10.1016/j.nbd.2022.105773}, pmid = {35623598}, issn = {1095-953X}, abstract = {Gut microbiota has implications in Central Nervous System (CNS) disorders. Our study systematically identified preclinical studies aimed to investigate the possible gut microbiota contribution in neuropathy and neuropathic pain. The systematic review is reported in accordance with PRISMA checklist and guidelines outlined updated to 2020. We included research articles reporting neuropathy-related behavioral evaluations and/or neurological scores coupled to gut microbiota analysis performed by high-throughput technologies in the last ten years. Two investigators performed a search through 3 electronic bibliographic databases for full-text articles (PubMed, Scopus, and EMBASE) and three registries (Prospero, SyRF, and bioRxiv), cross-references, and linear searches. We assessed the methodological quality via the CAMARADES checklist and appraised the heterogeneous body of evidence by narrative synthesis. In total, there were 19 eligible studies. The most of these reports showed significant changes in gut microbiota setting in neuropathy conditions. The major gut microbiome remodeling was through fecal microbiome transplantation. Mechanistic proof of the gut-CNS communication was achieved by measuring inflammatory mediators, metabolic products, or neurotransmitters. As a limitation, we found considerable heterogeneity across eligible studies. We conclude that the current understanding of preclinical findings suggested an association between neuropathy and/or neuropathic pain and gut microbiota modifications. Our analysis provides the basis for further studies targeting microbiota for managing symptoms of neuropathy or other neuroinflammation-based CNS disorders. The systematic review protocol was registered on the international database Prospero under the registration number (# 257628).}, }
@article {pmid35620724, year = {2022}, author = {Hu, Y and Ye, Z and Wu, M and She, Y and Li, L and Xu, Y and Qin, K and Hu, Z and Yang, M and Lu, F and Ye, Q}, title = {Corrigendum: The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {886105}, doi = {10.3389/fmed.2022.886105}, pmid = {35620724}, issn = {2296-858X}, abstract = {[This corrects the article DOI: 10.3389/fmed.2021.766126.].}, }
@article {pmid35619714, year = {2022}, author = {Zhang, B and Chen, T and Cao, M and Yuan, C and Reiter, RJ and Zhao, Z and Zhao, Y and Chen, L and Fan, W and Wang, X and Zhou, X and Li, C}, title = {Gut Microbiota Dysbiosis Induced by Decreasing Endogenous Melatonin Mediates the Pathogenesis of Alzheimer's Disease and Obesity.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {900132}, doi = {10.3389/fimmu.2022.900132}, pmid = {35619714}, issn = {1664-3224}, abstract = {Lifestyle choices, external environment, aging, and other factors influence the synthesis of melatonin. Although the physiological functions of melatonin have been widely studied in relation to specific organs, the systemic effects of endogenous melatonin reduction has not been reported. This study evaluates the systemic changes and possible pathogenic risks in an endogenous melatonin reduction (EMR) mouse model deficient in the rate limiting enzyme in melatonin production, arylalkylamine N-acetyltransferase (Aanat) gene. Using this model, we identified a new relationship between melatonin, Alzheimer's disease (AD), and gut microbiota. Systematic changes were evaluated using multi-omics analysis. Fecal microbiota transplantation (FMT) was performed to examine the role of gut microbiota in the pathogenic risks of EMR. EMR mice exhibited a pan-metabolic disorder, with significant transcriptome changes in 11 organs, serum metabolome alterations as well as microbiota dysbiosis. Microbiota dysbiosis was accompanied by increased gut permeability along with gut and systemic inflammation. Correlation analysis revealed that systemic inflammation may be related to the increase of Ruminiclostridium_5 relative abundance. 8-month-old EMR mice had AD-like phenotypes, including Iba-1 activation, A β protein deposition and decreased spatial memory ability. Moreover, EMR mice showed decreased anti stress ability, under high-fat diet, EMR mice had greater body weight and more obvious hepatic steatosis compared with WT group. FMT improved gut permeability, systemic inflammation, and AD-related phenotypes, while reducing obesity in EMR mice. Our findings suggest EMR causes systemic changes mediated by gut microbiota dysbiosis, which may be a pathogenic factor for AD and obesity, we further proved the gut microbiota is a potential target for the prevention and treatment of AD and obesity.}, }
@article {pmid35616308, year = {2022}, author = {Yan, X and Zhai, Y and Zhou, W and Qiao, Y and Guan, L and Liu, H and Jiang, J and Peng, L}, title = {Intestinal Flora Mediates Antiobesity Effect of Rutin in High-Fat-Diet Mice.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2100948}, doi = {10.1002/mnfr.202100948}, pmid = {35616308}, issn = {1613-4133}, abstract = {SCOPE: Intestinal flora plays a critical role in the development of diet-induced obesity and related metabolic complications. Rutin is a natural flavonoid with potential prebiotic effects on regulating the intestinal flora composition that is beneficial for host health. Therefore, we hypothesized that rutin supplementation has beneficial effects on high-fat-diet (HFD)-induced obesity and metabolic disorder through the modulation of intestinal flora in mice.
METHODS AND RESULTS: We investigated the obesity-alleviating property of rutin using 6-week-old C57BL/6J male mice fed on HFD with or without rutin supplementation for 16 weeks. Rutin supplementation effectively reduced body-weight gain, insulin resistance, and acted favorably on the intestinal barrier, thereby reducing endotoxemia and systemic inflammation. Sequencing of 16S rRNA genes from fecal samples indicated that rutin exerted modulatory effects on HFD-induced intestinal flora disorders (e.g., rutin decreased Firmicutes abundance and increased Bacteroidetes and Verrucomicrobia abundance). Antibiotic treatment and fecal microbiota transplantation further demonstrated that the salutary effects of rutin on obesity control were strongly dependent on the intestinal flora.
CONCLUSION: Rutin can be considered as a prebiotic agent for improving intestinal flora disorders and obesity-associated metabolic perturbations in obese individuals. This article is protected by copyright. All rights reserved.}, }
@article {pmid35613492, year = {2022}, author = {Fu, Y and Hu, J and Erasmus, MA and Johnson, TA and Cheng, HW}, title = {Effects of early-life cecal microbiota transplantation from divergently selected inbred chicken lines on growth, gut serotonin, and immune parameters in recipient chickens.}, journal = {Poultry science}, volume = {101}, number = {7}, pages = {101925}, doi = {10.1016/j.psj.2022.101925}, pmid = {35613492}, issn = {1525-3171}, abstract = {Recent studies have revealed that fecal microbiota transplantation exerts beneficial effects on modulating stress-related inflammation and gastrointestinal health of the host. The aim of this study was to examine if cecal microbiota transplantation (CMT) presents similar efficiency in improving the health status of egg-laying strain chickens. Chicken lines 63 and 72 divergently selected for resistance or susceptibility to Marek's disease were used as CMT donors. Eighty-four d-old male recipient chicks (a commercial DeKalb XL layer strain) were randomly assigned into 3 treatments with 7 replicates per treatment and 4 birds per replicate (n = 7): saline (control, CTRL), cecal solution of line 63 (63-CMT), and cecal solution of line 72 (72-CMT) for a 16-wk trial. Cecal transplant gavage was conducted once daily from d 1 to d 10, then boosted once weekly from wk 3 to wk 5. The results indicated that 72-CMT birds had the highest body weight and ileal villus/crypt ratio among the treatments at wk 5 (P ≤ 0.05); and higher heterophil/lymphocyte ratios than that of 63-CMT birds at wk 16 (P < 0.05). 72-CMT birds also had higher levels of plasma natural IgG and Interleukin (IL)-6 at wk 16, while 63-CMT birds had higher concentrations of ileal mucosal secretory IgA at wk 5 and plasma IL-10 at wk 16 (P < 0.05), with a tendency for lower mRNA abundance of splenic IL-6 and tumor necrosis factor (TNF)-α at wk 16 (P = 0.08 and 0.07, respectively). In addition, 72-CMT birds tended to have the lowest serotonin concentrations (P = 0.07) with the highest serotonin turnover in the ileum at wk 5 (P < 0.05). There were no treatment effects on the levels of plasma corticosterone and testosterone at wk 16 (P > 0.05). In conclusion, early postnatal CMT from different donors led to different patterns of growth and health status through the regulation of ileal morphological structures, gut-derived serotonergic activities, peripheral cytokines, and antibody production in recipient chickens.}, }
@article {pmid35610004, year = {2022}, author = {Zeyue, YU and Liyu, H and Zongyuan, LI and Jianhui, S and Hongying, C and Hairu, H and Xiaoqin, LI and Zhongchao, S and Hongmei, LI}, title = {Correlation between slow transit constipation and spleen deficiency, and gut microbiota: a pilot study.}, journal = {Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan}, volume = {42}, number = {3}, pages = {353-363}, doi = {10.19852/j.cnki.jtcm.20220408.002}, pmid = {35610004}, issn = {2589-451X}, support = {Z2021022//Fundamental Scientific Research Business Fees of Central Public Welfare Scientific Research Institutes of China Academy of Chinese Medical Sciences/ ; 81891010//National Natural Science Foundation Project: Study on the Authenticity of Traditional Chinese Medicine/ ; CI2021A04605//Science and Technology Innovation Project of China Academy of Chinese Medical Sciences: Efficacy Evaluation and Mechanism Exploration of Huashi Baidu Granule based on "multi-link and multi-target" in the Prevention and Treatment of Influenza Virus Infection/ ; ZZ15-WT-04//Basic Scientific Research Business Fee Project of Central Public Welfare Scientific Research Institutes of the Chinese Academy of Chinese Medical Sciences: Study on the Novel Coronavirus Pneumonia Mech-anism of Yiqi Zeng Fang and Huashi Baidu Granules/ ; }, abstract = {OBJECTIVE: To investigate the effect of slow transit constipation (STC) and spleen deficiency on gut microbiota, and the mechanism underlying the action that the positive drug Maren Runchang (MR) alleviates STC.
METHODS: STC was induced, using the cathartic method of Senna and the hunger-fullness disorder method, in ICR mice; one group of model mice was treated with MR (6.24 g/kg). The changes in the general condition, fecal parameters, D-xylose content in the serum, intestinal propulsion rate, and histopathology of the colon were assessed after STC induction in the control, model, and MR groups. Fecal microbiota transplantation (FMT) was performed from STC mice into pseudo germ-free mice. Changes in the contents of substance P (SP), vasoactive intestinal peptide (VIP), and gut microbiota in STC mice and pseudo germ-free mice were assessed after FMT.
RESULTS: Compared with the control group, the model mice showed the following results: the time of the first black stool was significantly longer (0.01), the number and weight of black stools were significantly reduced within 6 h (0.05), the D-xylose content in the serum was significantly reduced (< 0.05), the intestinal propulsion rate decreased (< 0.01), the content of VIP in colon tissue significantly increased (< 0.05), and SP content in the colon tissue significantly decreased (< 0.01); moreover, the colon showed significant inflame-mation and injury. Furthermore, the abundance of Firmicutes was increased, the abundance of Bacteroides decreased, and the abundance of decreased, while the abundance of the conditional pathogenic bacteria and Klebsiella increased. However, after treatment with MR, the time of the first black stool decreased (0.01), the number of black stools within 6 h increased, and the intestinal propulsion rate increased (< 0.05). Moreover, the content of D-xylose in the serum and the content of VIP in colon tissue significantly decreased (< 0.05), the content of SP in colon tissue significantly increased (< 0.01), and colon inflammation significantly improved. Additionally, the abundance of Firmicutes decreased, and the abundance of Bacteroides increased. The abundance of increased, and the abundance of decreased. In the model + FMT group, compared with control + FMT group, the content of VIP in colon tissue decreased (< 0.05), the content of SP in colon tissue significantly increased (< 0.01), and the abundance of probiotics, such as , decreased. In the MR + FMT group, compared with the model + FMT group, the content of VIP in colon tissue increased, the content of SP in colon tissue significantly decreased (< 0.01), and the abundance of probiotics increased.
CONCLUSIONS: STC mice with spleen deficiency show a decreased abundance of beneficial bacteria, such as , and an increased abundance of the conditional pathogenic bacteria . Furthermore, the mechanism of action of MR in treating STC may involve the regulation of intestinal movement, reduction of intestinal inflammation, elevation of intestinal absorption, and regulation of gut microbiota.}, }
@article {pmid35609771, year = {2022}, author = {Li, M and Guo, W and Dong, Y and Wang, W and Tian, C and Zhang, Z and Yu, T and Zhou, H and Gui, Y and Xue, K and Li, J and Jiang, F and Sarapultsev, A and Wang, H and Zhang, G and Luo, S and Fan, H and Hu, D}, title = {Beneficial effects of celastrol on immune balance by modulating gut microbiota in experimental ulcerative colitis.}, journal = {Genomics, proteomics & bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gpb.2022.05.002}, pmid = {35609771}, issn = {2210-3244}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and the mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR exerts the protective effects. We characterized the therapeutic effects and the potential mechanism of CSR in treating UC with histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation. CSR administration significantly ameliorated dextran sodium sulfate (DSS)-induced colitis in mice, which was evidenced by the recovered body weight, colon length, and the decreased disease activity index (DAI) score, as well as intestinal permeability. Meanwhile, CSR down-regulated the secretion of pro-inflammatory cytokines, up-regulated the anti-inflammatory mediators at both mRNA and protein levels, and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis. It's worth noting that all the therapeutic effects were exerted in a gut microbiota-dependent manner. Furthermore, CSR treatment increased the gut microbiota diversity and composition, and changed the metabolic productions, which was probably associated with the gut microbiota-mediated protective effects. In conclusion, this study provided the strong evidence that CSR may be a promising therapeutic drug for UC.}, }
@article {pmid35606800, year = {2022}, author = {Sun, Y and Sun, P and Hu, Y and Shan, L and Geng, Q and Gong, Y and Fan, H and Zhang, T and Zhou, Y}, title = {Elevated testicular apoptosis is associated with elevated sphingosine driven by gut microbiota in prediabetic sheep.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {121}, pmid = {35606800}, issn = {1741-7007}, support = {31900595//National Natural Science Foundation of China/ ; 32000582//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Apoptosis ; *Gastrointestinal Microbiome ; Humans ; Male ; *Melatonin ; Mice ; *Prediabetic State/complications ; Sheep ; Sphingosine ; Testis ; }, abstract = {BACKGROUND: Men with prediabetes often exhibit concomitant low-quality sperm production or even infertility, problems which urgently require improved therapeutic options. In this study, we have established a sheep model of diet-induced prediabetes that is associated with spermatogenic defects and have explored the possible underlying metabolic causes.
RESULTS: We compared male sheep fed a normal diet with those in which prediabetes was induced by a rich diet and with a third group in which the rich diet was supplemented by melatonin. Only the rich diet group had symptoms of prediabetes, and in these sheep, we found impaired spermatogenesis characterized by a block in the development of round spermatids and an increased quantity of testicular apoptotic cells. Comparing the gut microbiomes and intestinal digest metabolomes of the three groups revealed a distinctive difference in the taxonomic composition of the microbiota in prediabetic sheep, and an altered metabolome, whose most significant feature was altered sphingosine metabolism; elevated sphingosine was also found in blood and testes. Administration of melatonin alleviated the symptoms of prediabetes, including those of impaired spermatogenesis, while restoring a more normal microbiota and metabolic levels of sphingosine. Fecal microbiota transplantation from prediabetic sheep induced elevated sphingosine levels and impaired spermatogenesis in recipient mice, indicating a causal role of gut microbiota in these phenotypes.
CONCLUSIONS: Our results point to a key role of sphingosine in the disruption of spermatogenesis in prediabetic sheep and suggest it could be a useful disease marker; furthermore, melatonin represents a potential prebiotic agent for the treatment of male infertility caused by prediabetes.}, }
@article {pmid35604764, year = {2022}, author = {Benítez-Páez, A and Hartstra, AV and Nieuwdorp, M and Sanz, Y}, title = {Species- and strain-level assessment using rrn long-amplicons suggests donor's influence on gut microbial transference via fecal transplants in metabolic syndrome subjects.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2078621}, doi = {10.1080/19490976.2022.2078621}, pmid = {35604764}, issn = {1949-0984}, abstract = {Fecal microbiota transplantation (FMT) is currently used for treating Clostridium difficile infection and explored for other clinical applications in experimental trials. However, the effectiveness of this therapy could vary, and partly depend on the donor's bacterial species engraftment, whose evaluation is challenging because there are no cost-effective strategies for accurately tracking the microbe transference. In this regard, the precise identification of bacterial species inhabiting the human gut is essential to define their role in human health unambiguously. We used Nanopore-based device to sequence bacterial rrn operons (16S-ITS-23S) and to reveal species-level abundance changes in the human gut microbiota of a FMT trial. By assessing the donor and recipient microbiota before and after FMT, we further evaluated whether this molecular approach reveals strain-level genetic variation to demonstrate microbe transfer and engraftment. Strict control over sequencing data quality and major microbiota covariates was critical for accurately estimating the changes in gut microbial species abundance in the recipients after FMT. We detected strain-level variation via single-nucleotide variants (SNVs) at rrn regions in a species-specific manner. We showed that it was possible to explore successfully the donor-bacterial strain (e.g., Parabacteroides merdae) engraftment in recipients of the FMT by assessing the nucleotide frequencies at rrn-associated SNVs. Our findings indicate that the engraftment of donors' microbiota is to some extent correlated with the improvement of metabolic health in recipients and that parameters such as the baseline gut microbiota configuration, sex, and age of donors should be considered to ensure the success of FMT in humans. The study was prospectively registered at the Dutch Trial registry - NTR4488 (https://www.trialregister.nl/trial/4488).}, }
@article {pmid35601099, year = {2022}, author = {Wang, J and Zhou, X and Li, X and Guo, W and Zhu, Q and Zhu, B and Lu, Y and Zheng, X and Yang, D and Wang, B}, title = {Fecal Microbiota Transplantation Alters the Outcome of Hepatitis B Virus Infection in Mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {844132}, doi = {10.3389/fcimb.2022.844132}, pmid = {35601099}, issn = {2235-2988}, abstract = {The susceptibility of mice to hepatitis B virus (HBV) infection depends on their genetic background. The gut microbiota modulates the antiviral immune response in the liver and plays a protective role against HBV infection. However, whether HBV infection outcomes depend on the gut microbiota remains unclear. In this study, we assessed the gut microbiota composition in naïve BALB/c and C57BL/6 mice using 16S rRNA gene sequencing. The gut microbiota in BALB/c mice was depleted using broad-spectrum antibiotics (ABX) and then reconstituted with fecal microbiota from naïve BALB/c or C57BL/6 mice to evaluate the effect of fecal microbiota transplantation (FMT) on the outcomes of and immune response to HBV infection. We found that HBV infection outcomes and the gut microbiota composition differed between BALB/c and C57BL/6 mice. Commensal bacteria from the fecal microbiota selectively colonized the guts of ABX-treated BALB/c mice. Mice receiving fecal microbiota from BALB/c or C57BL/6 mice displayed different HBV infection outcomes. The fecal microbiota from C57BL/6 mice induced immune tolerance in the liver and prolonged HBV infection. In conclusion, HBV infection outcomes in mice are determined by the host genetic background and gut microbiota composition. Reconstitution of the gut microbiota by FMT can alter the susceptibility to HBV infection in mice.}, }
@article {pmid35600753, year = {2022}, author = {Singh, R and Stogios, N and Smith, E and Lee, J and Maksyutynsk, K and Au, E and Wright, DC and De Palma, G and Graff-Guerrero, A and Gerretsen, P and Müller, DJ and Remington, G and Hahn, M and Agarwal, SM}, title = {Gut microbiome in schizophrenia and antipsychotic-induced metabolic alterations: a scoping review.}, journal = {Therapeutic advances in psychopharmacology}, volume = {12}, number = {}, pages = {20451253221096525}, doi = {10.1177/20451253221096525}, pmid = {35600753}, issn = {2045-1253}, abstract = {Schizophrenia (SCZ) is a severe mental disorder with high morbidity and lifetime disability rates. Patients with SCZ have a higher risk of developing metabolic comorbidities such as obesity and diabetes mellitus, leading to increased mortality. Antipsychotics (APs), which are the mainstay in the treatment of SCZ, increase the risk of these metabolic perturbations. Despite extensive research, the mechanism underlying SCZ pathophysiology and associated metabolic comorbidities remains unclear. In recent years, gut microbiota (GMB) has been regarded as a 'chamber of secrets', particularly in the context of severe mental illnesses such as SCZ, depression, and bipolar disorder. In this scoping review, we aimed to investigate the underlying role of GMB in the pathophysiology of SCZ and metabolic alterations associated with APs. Furthermore, we also explored the therapeutic benefits of prebiotic and probiotic formulations in managing SCZ and AP-induced metabolic alterations. A systematic literature search yielded 46 studies from both preclinical and clinical settings that met inclusion criteria for qualitative synthesis. Preliminary evidence from preclinical and clinical studies indicates that GMB composition changes are associated with SCZ pathogenesis and AP-induced metabolic perturbations. Fecal microbiota transplantation from SCZ patients to mice has been shown to induce SCZ-like behavioral phenotypes, further supporting the plausible role of GMB in SCZ pathogenesis. This scoping review recapitulates the preclinical and clinical evidence suggesting the role of GMB in SCZ symptomatology and metabolic adverse effects associated with APs. Moreover, this scoping review also discusses the therapeutic potentials of prebiotic/probiotic formulations in improving SCZ symptoms and attenuating metabolic alterations related to APs.}, }
@article {pmid35598286, year = {2022}, author = {Batra, M and Bhatnager, R and Kumar, A and Suneja, P and Dang, AS}, title = {Interplay between PCOS and Microbiome: The road less travelled.}, journal = {American journal of reproductive immunology (New York, N.Y. : 1989)}, volume = {}, number = {}, pages = {}, doi = {10.1111/aji.13580}, pmid = {35598286}, issn = {1600-0897}, abstract = {: Polycystic ovarian syndrome (PCOS) is a complicated neuro-endocrinal, reproductive, and metabolic condition. It encompasses patterns such as hyperandrogenism, recurrent cysts triggered by steroidogenic functional aberrations in the ovaries, overweight, chronic inflammation, and more. The underlying cause of this heterogeneous illness is obscure, although it is suspected to be driven by a blend of environmental and hereditary factors. In recent years, the connection between the microbiome and PCOS has been acknowledged and is thought to be involved in the genesis of the syndrome's emergence. Microbiota vary in different pathological features of PCOS, and fundamental pathways linked to their involvement in the commencement of diverse clinical presentations in PCOS open up a new avenue for its management . Prebiotic, probiotic, synbiotic, and fecal-microbiota-transplant, by promoting eubiosis and nullifying the effect caused by the altered microbial profile in PCOS women, can aid in management of diverse phenotypes associated with the syndrome. These microbiota-mediated treatments improve PCOS women's metabolic, inflammatory, and hormonal profiles. However, more studies are needed to elucidate the mechanisms that drive this positive effect . This article is protected by copyright. All rights reserved.}, }
@article {pmid35596224, year = {2022}, author = {Chen, H and Ye, C and Cai, B and Zhang, F and Wang, X and Zhang, J and Zhang, Z and Guo, Y and Yao, Q}, title = {Berberine inhibits intestinal carcinogenesis by suppressing intestinal pro-inflammatory genes and oncogenic factors through modulating gut microbiota.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {566}, pmid = {35596224}, issn = {1471-2407}, support = {LY21H290001//Natural Science Foundation of Zhejiang Province/ ; Z20H290002//Natural Science Foundation of Zhejiang Province/ ; 2021KY569//Medical and Health Platform Program of Zhejiang Province/ ; 2017-XK-A09//Zhejiang Provincial Project for the key discipline of Traditional Chinese Medicine/ ; 82074201//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The role of Berberine (BBR) in colorectal cancer (CRC) and gut microbiota has begun to appreciate. However, there was no direct evidence confirm that the gut microbiota regulated by BBR could inhibit CRC. This report investigated the effect of stool from BBR treated subjects and its effect on CRC.
METHODS: A mouse model for CRC was developed using azoxymethane (AOM) and dextran sulfate sodium (DSS). Intestinal tissue from affected mice were used to determine the efficacy of BBR against CRC. Stool samples were collected for the 16s rRNA gene sequencing and fecal microbiota transplantation (FMT). Finally, the mechanism of gut microbiota from BBR treated mice on CRC was explored using immunohistochemistry, RNA-Sequencing, quantitative RT-PCR, and western blot analyses.
RESULTS: BBR significantly reduced intestinal tumor development. The richness of gut microbiota were notably decreased by BBR. Specifically, the relative abundance of beneficial bacteria (Roseburia, Eubacterium, Ruminococcaceae, and Firmicutes_unclassified) was increased while the level of bacteria (Odoribacter, Muribaculum, Mucispirillum, and Parasutterella) was decreased by BBR treatment. FMT experiment determined that the mice fed with stool from BBR treated AOM/DSS mice demonstrated a relatively lower abundance of macroscopic polyps and a significantly lower expression of β-catenin, and PCNA in intestinal tissue than mice fed with stool from AOM/DSS mice. Mechanistically, intestinal tissue obtained from mice fed with stool from BBR treated AOM/DSS mice demonstrated a decreased expression of inflammatory cytokines including interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), C-C motif chemokine 1 (Ccl1), Ccl6, and C-X-C motif ligand (Cxcl9). In addition, the NF-κB expression was greatly suppressed in mice fed with stool from BBR treated AOM/DSS mice. Real-time PCR arrays revealed a down-regulation of genes involved in cell proliferation, angiogenesis, invasiveness, and metastasis in mice fed with stool from BBR treated AOM/DSS mice.
CONCLUSIONS: Stool obtained from BBR treated AOM/DSS mice was able to increase colon length while simultaneously decreasing the density of macroscopic polyps, cell proliferation, inflammatory modulators and the expression of NF-κB. Therefore, it was concluded that suppression of pro-inflammatory genes and carcinogens factors by modulating gut microbiota was an important pathway for BBR to inhibit tumor growth in conventional mice.}, }
@article {pmid35595837, year = {2022}, author = {Quaranta, G and Mandrioli, J and Bibbò, S and Guarnaccia, A and Fancello, G and Simonini, C and Amedei, A and Niccolai, E and Nannini, G and Cammarota, G and Sanguinetti, M and Masucci, L}, title = {Rummeliibacillus suwonensis: First Time Isolation from Human Feces by Culturomics.}, journal = {Current microbiology}, volume = {79}, number = {7}, pages = {197}, pmid = {35595837}, issn = {1432-0991}, support = {RF-2016-02361616.//italian ministry of health/ ; }, abstract = {Gut microbiota is a complex ecosystem composed by trillions of microorganisms that are crucial for human health or disease status. Currently, there are two methodological options to explore its complexity: metagenomics and culturomics. Culturomics is an approach that uses multiple culture conditions (days of incubation, enrichment factors and growth temperature) and MALDI-TOF mass spectrometry for the identification of bacterial species and sequencing when this method fails. In this paper, we describe how Colturomic's protocol has allowed the first isolation in human sample of Rummeliibacillus suwonensis, a Gram positive, facultative anaerobe bacterium. The bacterium was isolated from feces of a 69 years old male with amyotrophic lateral sclerosis (ALS) recruited for a clinical trial assessing safety and efficacy of fecal microbiota transplantation in ALS. The first isolation of the microorganism dates back to 2013 from the soil of a South Korean mountain area. In this report, morphological description, biochemical characterization and antibiotic susceptibility tests were performed to outline the bacterial properties.}, }
@article {pmid35593345, year = {2022}, author = {Bashir, R and Wani, IA and Ganie, MA}, title = {Insights into new therapeutic approaches for the treatment and management of polycystic ovary syndrome: An updated review.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/1381612828666220518150754}, pmid = {35593345}, issn = {1873-4286}, abstract = {BACKGROUND: Polycystic ovary syndrome (PCOS) is a long-term, highly prevalent, complex heterogeneous, polygenic endocrine disorder characterized by both metabolic and reproductive disorders. It affects 6-23% of reproductive age women globally.
OBJECTIVE: This review aims to facilitate an understanding of novel PCOS management approaches and highlights the results from relevant interventional studies from animal and human studies.
METHODS: Manual search on PubMed, Cochrane, Scopus databases was performed for relevant articles, preclinical and clinical trials based on related keywords.
RESULTS: According to a multitude of studies, PCOS has evolved over time, but a substantial lag remains in management approaches. New insights into the cross-talk between muscle, brain, fat, and ovaries pointed out new therapeutic targets. This review has highlighted the efficacy of a wide spectrum of novel therapeutic agents [Phosphodiesterase-4 Inhibitors, Glucagon-like peptide-1 receptor agonists, nutritional supplements (Vitamins D and K, omega-3, prebiotics, probiotics and synbiotics), fecal microbiota transplantation (FMT) and intestinal cytokine IL-22] as PCOS therapeutic options. These novel therapies combine anti-inflammatory, insulin sensitizing, anti-obesity, and restoration of the gut microbiota and thus hold the potential to address the basic pathogenic mechanisms of PCOS.
CONCLUSION: Exhaustive, multicentric and multiethnic studies are vital to generate a network of normative data to better figure out the PCOS trajectory and change prognostic outcomes. Preclinical and clinical data is warranted to corroborate the new therapeutics and direct health care resources accordingly.}, }
@article {pmid34992261, year = {2022}, author = {Sorbara, MT and Pamer, EG}, title = {Microbiome-based therapeutics.}, journal = {Nature reviews. Microbiology}, volume = {20}, number = {6}, pages = {365-380}, pmid = {34992261}, issn = {1740-1534}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Health Promotion ; Humans ; *Microbiota ; }, abstract = {Symbiotic microorganisms inhabiting the gastrointestinal tract promote health by decreasing susceptibility to infection and enhancing resistance to a range of diseases. In this Review, we discuss our increasing understanding of the impact of the microbiome on the mammalian host and recent efforts to culture and characterize intestinal symbiotic microorganisms that produce or modify metabolites that impact disease pathology. Manipulation of the intestinal microbiome has great potential to reduce the incidence and/or severity of a wide range of human conditions and diseases, and the biomedical research community now faces the challenge of translating our understanding of the microbiome into beneficial medical therapies. Our increasing understanding of symbiotic microbial species and the application of ecological principles and machine learning are providing exciting opportunities for microbiome-based therapeutics to progress from faecal microbiota transplantation to the administration of precisely defined and clinically validated symbiotic microbial consortia that optimize disease resistance.}, }
@article {pmid35589257, year = {2022}, author = {Bajaj, JS and Ng, SC and Schnabl, B}, title = {Promises of microbiome-based therapies.}, journal = {Journal of hepatology}, volume = {76}, number = {6}, pages = {1379-1391}, doi = {10.1016/j.jhep.2021.12.003}, pmid = {35589257}, issn = {1600-0641}, abstract = {Humans harbour large quantities of microbes, including bacteria, fungi, viruses and archaea, in the gut. Patients with liver disease exhibit changes in the intestinal microbiota and gut barrier dysfunction. Preclinical models demonstrate the importance of the gut microbiota in the pathogenesis of various liver diseases. In this review, we discuss how manipulation of the gut microbiota can be used as a novel treatment approach for liver disease. We summarise current data on untargeted approaches, including probiotics and faecal microbiota transplantation, and precision microbiome-centered therapies, including engineered bacteria, postbiotics and phages, for the treatment of liver diseases.}, }
@article {pmid35587527, year = {2022}, author = {Yan, S and Chen, J and Zhu, L and Guo, T and Qin, D and Hu, Z and Han, S and Zhou, Y and Akan, OD and Wang, J and Luo, F and Lin, Q}, title = {Oryzanol Attenuates High Fat and Cholesterol Diet-Induced Hyperlipidemia by Regulating the Gut Microbiome and Amino Acid Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c00885}, pmid = {35587527}, issn = {1520-5118}, abstract = {Hyperlipidemia is intricately associated with the dysregulation of gut microbiota and host metabolomes. This study explored the antihyperlipidemic function of oryzanol and investigated whether the function of oryzanol affected the gut microbiome and its related metabolites. Hamsters were fed a standard diet (Control) and a high fat and cholesterol (HFCD) diet with or without oryzanol, separately. Our results showed that oryzanol significantly decreased HFCD-induced fat accumulation, serum total cholesterol, low-density lipoprotein cholesterol (LDL-c), LDL-c/HDL-c ratio, triglyceride, and liver steatohepatitis, attenuated HFCD-induced gut microbiota alterations, and altered amino acid concentrations in feces and the liver. We investigated the role of the gut microbiota in the observed beneficial effects; the protective effects of oryzanol were partly diminished by suppressing the gut bacteria of hamsters after using antibiotics. A fecal microbiota transplantation experiment was carried out by transplanting the feces from HFCD group hamsters or hamsters given oryzanol supplementation (as a donor hamster). Our results showed that administering the fecal liquid from oryzanol-treated hamsters attenuated HFCD-induced hyperlipidemia, significantly decreased the abundance of norank_f__Erysipelotrichaceae, norank_f__Eubacteriaceae, and norank_f__Oscillospiraceae and the concentration of tyrosine. These outcomes are significantly positively correlated with serum lipid concentration. This study illustrated that gut microbiota is the target of oryzanol in the antihyperlipidemic effect.}, }
@article {pmid35585088, year = {2022}, author = {Yan, J and Liao, C and Taylor, BP and Fontana, E and Amoretti, LA and Wright, RJ and Littmann, ER and Dai, A and Waters, N and Peled, JU and Taur, Y and Perales, MA and Siranosian, BA and Bhatt, AS and van den Brink, MRM and Pamer, EG and Schluter, J and Xavier, JB}, title = {A compilation of fecal microbiome shotgun metagenomics from hematopoietic cell transplantation patients.}, journal = {Scientific data}, volume = {9}, number = {1}, pages = {219}, pmid = {35585088}, issn = {2052-4463}, support = {R01 AI137269/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; }, abstract = {Hospitalized patients receiving hematopoietic cell transplants provide a unique opportunity to study the human gut microbiome. We previously compiled a large-scale longitudinal dataset of fecal microbiota and associated metadata, but we had limited that analysis to taxonomic composition of bacteria from 16S rRNA gene sequencing. Here we augment those data with shotgun metagenomics. The compilation amounts to a nested subset of 395 samples compiled from different studies at Memorial Sloan Kettering. Shotgun metagenomics describes the microbiome at the functional level, particularly in antimicrobial resistances and virulence factors. We provide accession numbers that link each sample to the paired-end sequencing files deposited in a public repository, which can be directly accessed by the online services of PATRIC to be analyzed without the users having to download or transfer the files. Then, we show how shotgun sequencing enables the assembly of genomes from metagenomic data. The new data, combined with the metadata published previously, enables new functional studies of the microbiomes of patients with cancer receiving bone marrow transplantation.}, }
@article {pmid35584163, year = {2022}, author = {Benech, N and Galperine, T and Sokol, H and , }, title = {SER-109 for Recurrent Clostridioides difficile Infection.}, journal = {The New England journal of medicine}, volume = {386}, number = {20}, pages = {1956-1957}, doi = {10.1056/NEJMc2202493}, pmid = {35584163}, issn = {1533-4406}, }
@article {pmid35579462, year = {2022}, author = {Renu, S and Deblais, L and Patil, V and Schrock, J and Kathayat, D and Srivastava, V and Feliciano-Ruiz, N and Han, Y and Ramesh, A and Lakshmanappa, YS and Ghimire, S and Dhakal, S and Rajashekara, G and Renukaradhya, GJ}, title = {Gut Microbiota of Obese Children Influences Inflammatory Mucosal Immune Pathways in the Respiratory Tract to Influenza Virus Infection: Optimization of an Ideal Duration of Microbial Colonization in a Gnotobiotic Pig Model.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0267421}, doi = {10.1128/spectrum.02674-21}, pmid = {35579462}, issn = {2165-0497}, abstract = {The impact of obesity on the human microbiota, immune maturation, and influenza virus infection has not been yet established in natural host animal models of influenza. In this study, gnotobiotic (Gn) pigs were colonized with human fecal microbiota (HFM) of obese (oHFM) or healthy lean (hHFM) children and infected at different periods (2-, 3-, and 5-weeks post-transplantation) using a zoonotic influenza virus strain. The infected oHFM pigs were characterized by lower levels of Firmicutes (Lactococcus, Lactobacillus, Turicibacter, and Streptococcus) and Actinobacteria (Bifidobacterium), which was associated with higher levels of Proteobacteria (Klebsiella), Bacteroidetes, and Verrucomicrobia (Akkermansia) compared with the infected hHFM group (P < 0.01). Furthermore, these genera significantly correlated with the expression of immune effectors, immune regulators, and inflammatory mediators, and displayed opposite trends between oHFM and hHFM groups (P < 0.01). The lymphoid and myeloid immune cell frequencies were differently modulated by the oHFM and hHFM colonization, especially apparent in the 5-weeks HFM colonized piglets. In addition, oHFM group had higher pro-inflammatory cytokines (IL-6, IL-12, TNF-α, and IFNγ) gene expression in the respiratory tract compared with the hHFM colonized pigs was detected. In conclusion, pigs colonized for longer duration, established oHFM increased the immune maturation favoring the activation of inflammatory mediators, however, the influenza virus load remained comparable with the hHFM group. Further, a longer duration of microbial colonization (5 weeks) may be required to reveal the impact of microbiome on the host immune maturation and susceptibility to influenza virus infection in the humanized Gn pig model. IMPORTANCE The diversity of gut microbiome of obese people differs markedly from that of lean healthy individuals which, in turn, influences the severity of inflammatory diseases because of differential maturation of immune system. The mouse model provides crucial insights into the mechanism(s) regulating the immune systems mediated by the gut microbiota but its applicability to humans is questionable because immune cells in mice are poorly activated in microbiota humanized mice. Several important strains of Bifidobacterium, Lactobacillus, and Clostridium fails to colonize the murine gut. Thus, understanding the role of certain important commensal gut bacterial species influences upon health and disease, a suitable large animal model like pig that supports the growth and colonization of most of the important human gut bacteria and possess comparable immunology and physiology to humans is beneficial to improve health.}, }
@article {pmid35577712, year = {2022}, author = {Piawah, S and Walker, EJ and Van Blarigan, EL and Atreya, CE}, title = {The Gut Microbiome in Colorectal Cancer.}, journal = {Hematology/oncology clinics of North America}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.hoc.2022.03.001}, pmid = {35577712}, issn = {1558-1977}, abstract = {The gut microbiome is important in human health and disease. Recent studies have begun to elucidate its specific role in colorectal cancer. The gut microbiome seems to play an integral role in colorectal cancer initiation and progression, and oncologic drug metabolism and toxicity. This review examines the associations between the gut microbiome and colorectal cancer initiation, progression, and oncologic drug metabolism, highlighting proposed mechanisms and landmark publications in this field. It also discusses potential methods of modulating the gut microbiome, underscoring the gaps in current understanding, and ends with a clinically relevant overview of microbiome research considerations and study design.}, }
@article {pmid35574751, year = {2022}, author = {Yan, Y and Peng, X and Chen, Y}, title = {[Fecal microbiota transplantation in the treatment of acute intestinal pseudo obstruction secondary to intracerebral hemorrhage: a case report and literature review].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {34}, number = {3}, pages = {306-310}, doi = {10.3760/cma.j.cn121430-20220225-00179}, pmid = {35574751}, issn = {2095-4352}, abstract = {OBJECTIVE: To analyze the clinical effects of fecal microbiota transplantation (FMT) on the treatment of acute intestinal pseudo obstruction (AIPO) secondary to intracerebral hemorrhage.
METHODS: The clinical data of a patient with AIPO secondary to intracerebral hemorrhage who was admitted to Nanfang Hospital of Southern Medical University was analyzed. The flora compositon between donor and patient was compared, finding the changes of intestinal flora before and after FMT (day 0 and day 25).
RESULTS: The main clinical findings in the patient were serious bloating, expansion of the intestinal canal and intra-abdominal hypertension. A week of conventional therapy was not effective, and the symptoms became progressively worse, affecting respiratory function.The result of fecal flora suggested the intestinal microbiota dybiosis, so FMT was attempted. After FMT, the patient's gastrointestinal symptoms were significantly relieved, and there were no further episodes within 25 days. The new result of fecal flora showed that the flora colonizing the intestine was dominated by Akkermansia and Bifidobacterium, with a significant decrease in potential pro-inflammatory and gas-producing bacteria and an increased gut microbiota diversity. The results trended to be partly consistent with the donor at 25 days after FMT: at the phylum level, the relative abundance of Bacterioidetes, Vereucomicrobia, Firmicutes and Actinobacteria were increased while Proteobacteria was decreased; at the class level, the relative abundance of Verrucomicrobiae, Bacterioidia, Actinobacteria, Coriobacteriia and Clostridia were increased and Gammaproteobacteria was decreased; at the order level, the relative abundance of Bacterioidales, Verrucomicrobiales, Clostridiale, Coriobacteriales were increased and Betaproteobacteriales, Enterobacteriales were decreased; at the family level, the relative abundance of Bifidobacteriaceae, Akkermansiaceae, Ruminococcaceae were increased and Enterobacteriaceae was decreased; at the genus level, the relative abundance of Akkermansia, Bifidobacterium were increased and Escherichia-Shigella, Klebsiella were decreased. At 1-year follow-up, the patient lived with self-care and scored 5 points in Glasgow outcome scale (GOS).
CONCLUSIONS: FMT may provide clinical benefit in treated patients with AIPO secondary to intracerebral hemorrhage, probably by regulating the intestinal microflora, and re-establishing proper intestinal barrier, to maintain intestinal homeostasis.}, }
@article {pmid35572534, year = {2022}, author = {Zhao, H and Lyu, Y and Zhai, R and Sun, G and Ding, X}, title = {Metformin Mitigates Sepsis-Related Neuroinflammation via Modulating Gut Microbiota and Metabolites.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {797312}, doi = {10.3389/fimmu.2022.797312}, pmid = {35572534}, issn = {1664-3224}, abstract = {Gut microbiota affects the functions of brains. However, its mechanism in sepsis remains unclear. This study evaluated the effect of metformin on ameliorating sepsis-related neurodamage by regulating gut microbiota and metabolites in septic rats. Cecal ligation and puncture (CLP) was used to establish the sepsis-related neurodamage animal models. Metformin therapy by gavage at 1 h after CLP administration was followed by fecal microbiota transplantation (FMT) to ensure the efficacy and safety of metformin on the sepsis-related neurodamage by regulating gut microbiota. The gut microbiota and metabolites were conducted by 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry metabolomic analysis. The brain tissue inflammation response was analyzed by histopathology and reverse transcription-polymerase chain reaction (RT-PCR). This study reported brain inflammatory response, hemorrhage in sepsis-related neurodamage rats compared with the control group (C group). Surprisingly, the abundance of gut microbiota slightly increased in sepsis-related neurodamage rats than C group. The ratio of Firmicutes/Bacteroidetes was significantly increased in the CLP group than the C group. However, no difference was observed between the CLP and the metformin-treated rats (MET group). Interestingly, the abundance of Escherichia_Shigella increased in the MET group than the C and CLP groups, while Lactobacillaceae abundance decreased. Furthermore, Prevotella_9, Muribaculaceae, and Alloprevotella related to short-chain fatty acids production increased in the sepsis-related neurodamage of metformin-treated rats. Additionally, Prevotella_9 and Muribaculaceae correlated positively to 29 metabolites that might affect the inflammatory factors in the brain. The FMT assay showed that metformin improved sepsis-related neurodamage by regulating the gut microbiota and metabolites in septic rats. The findings suggest that metformin improves the sepsis-related neurodamage through modulating the gut microbiota and metabolites in septic rats, which may be an effective therapy for patients with sepsis-related neurodamage.}, }
@article {pmid35572528, year = {2022}, author = {Kawasoe, J and Uchida, Y and Kawamoto, H and Miyauchi, T and Watanabe, T and Saga, K and Tanaka, K and Ueda, S and Terajima, H and Taura, K and Hatano, E}, title = {Propionic Acid, Induced in Gut by an Inulin Diet, Suppresses Inflammation and Ameliorates Liver Ischemia and Reperfusion Injury in Mice.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {862503}, doi = {10.3389/fimmu.2022.862503}, pmid = {35572528}, issn = {1664-3224}, abstract = {Liver ischemia and reperfusion injury (IRI) is one of the obstacles in liver surgery such as liver resection and transplantation. In this study, we investigated the preventive effect on mouse liver IRI by feeding mice with inulin, which is a heterogeneous blend of indigestible fructose polymer. Mice were fed either a control ordinary diet (CD) or an inulin diet (ID) containing 5% inulin in the CD, for 14 days before the ischemia and reperfusion (IR) maneuver. IR induced-liver damages were significantly ameliorated in the ID group, compared with those in the CD group. Feeding mice with an ID, but not a CD, elevated levels of Bacteroidetes among gut microbiota, and especially increased Bacteroides acidifaciens in mouse feces, which resulted in significant elevation of short-chain fatty acids (SCFAs) in the portal vein of mice. Among SCFAs, propionic acid (PA) was most significantly increased. The microbial gene functions related to PA biosynthesis were much higher in the fecal microbiome of the ID group compared to the CD. However, the action of PA on liver IRI has not been yet clarified. Direct intraperitoneal administration of PA alone prior to the ischemia strongly suppressed liver cell damages as well as inflammatory responses caused by liver IR. Furthermore, PA suppressed the secretion of inflammatory cytokines from peritoneal macrophages stimulated in vitro through TLR-4 with high-mobility group box 1 protein (HMGB-1), known to be released from apoptotic liver cells during the IR insult. The present study shows that PA may play a key role in the inulin-induced amelioration of mouse liver IRI.}, }
@article {pmid35571974, year = {2022}, author = {Al, KF and Craven, LJ and Gibbons, S and Parvathy, SN and Wing, AC and Graf, C and Parham, KA and Kerfoot, SM and Wilcox, H and Burton, JP and Kremenchutzky, M and Morrow, SA and Casserly, C and Meddings, J and Sharma, M and Silverman, MS}, title = {Fecal microbiota transplantation is safe and tolerable in patients with multiple sclerosis: A pilot randomized controlled trial.}, journal = {Multiple sclerosis journal - experimental, translational and clinical}, volume = {8}, number = {2}, pages = {20552173221086662}, doi = {10.1177/20552173221086662}, pmid = {35571974}, issn = {2055-2173}, abstract = {Background: Patients with MS have an altered gut microbiota compared to healthy individuals, as well as elevated small intestinal permeability, which may be contributing to the development and progression of the disease.
Objective: We sought to investigate if fecal microbiota transplantation was safe and tolerable in MS patients and if it could improve abnormal intestinal permeability.
Methods: Nine patients with MS were recruited and provided monthly FMTs for up to six months. The primary outcome investigated was change in peripheral blood cytokine concentrations. The secondary outcomes were gut microbiota composition, intestinal permeability, and safety (assessed with EDSS and MRI).
Results: The study was terminated early and was subsequently underpowered to assess whether peripheral blood cytokines were altered following FMTs. FMTs were safe in this group of patients. Two of five patients had elevated small intestinal permeability at baseline that improved to normal values following FMTs. Significant, donor-specific, beneficial alterations to the MS patient gut microbiota were observed following FMT.
Conclusion: FMT was safe and tolerable in this cohort of RRMS patients, may improve elevated small intestinal permeability, and has the potential to enrich for an MS-protective microbiota. Further studies with longer follow-up and larger sample sizes are required to determine if FMT is a suitable therapy for MS.}, }
@article {pmid35568180, year = {2022}, author = {Chatterjee, G and Negi, S and Basu, S and Faintuch, J and O'Donovan, A and Shukla, P}, title = {Microbiome systems biology advancements for natural well-being.}, journal = {The Science of the total environment}, volume = {}, number = {}, pages = {155915}, doi = {10.1016/j.scitotenv.2022.155915}, pmid = {35568180}, issn = {1879-1026}, abstract = {Over the course of years all data from epidemiological, physiological and omics have suggested that the microbial communities play a considerable role in modulating human health. These set of microorganisms residing in the human intestine collectively known as microbiota presents a genetic repertoire that is higher in magnitude than the human genome. They play an essential role in host immunity and neuronal signaling. Rapid enhancement of sequence based screening and humanized gnotobiotic model has sparked a great deal of interest among scientists to interact the dynamic interactions of the commensal bacteria. This review focuses on systemic analysis of the gut microbiome to decipher the complexity of the host-microbe intercommunication and gives a special emphasis on the evolution of targeted precision medicine through microbiome engineering. In addition, we have also provided a comprehensive understanding of how interconnection between metabolism and biochemical reactions in a specific organism can be obtained from a metabolic network or a flux balance analysis and can help in the identification of a particular metabolite, by combining multiple datasets. The review highlights on how the genetic modification of the critical components and programming the resident microflora can be employed for targeted precision medicine. Inspite of the ongoing debate on the utility of gut microbiome we have explored on the probable new therapeutic avenues like FMT (Fecal microbiota transplant) can be utilized. This review also recapitulates integrating human-relevant 3D cellular models coupled with computational models and the metadata obtained from interventional and epidemiological studies may decipher the complex interactome of diet-microbiota-disease pathophysiology. In addition, it will also open new avenues for the development of therapeutics derived from microbiome or implementation of personalized nutrition. In addition, the identification of biomarkers can also help towards the development of new diagnostic tools and eventually will lead to strategic management of the disease.}, }
@article {pmid35563189, year = {2022}, author = {Fan, Z and Zhang, X and Shang, Y and Zou, M and Zhou, M and E, Q and Fei, S and Chen, W and Li, J and Zhang, X and Liu, X}, title = {Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries.}, journal = {International journal of molecular sciences}, volume = {23}, number = {9}, pages = {}, doi = {10.3390/ijms23094797}, pmid = {35563189}, issn = {1422-0067}, abstract = {Obesity induced by a high-fat diet (HFD) leads to the excessive consumption of primordial follicles (PFs) in the ovaries. There is systemic chronic inflammation under HFD conditions, but no previous studies have explored whether there is a certain causal relationship between HFD-induced chronic inflammation and the overactivation of PFs. Here, we showed that HFD causes disorders of intestinal microflora in mice, with five Gram-negative bacteria showing the most profound increase at the genus level compared to the normal diet (ND) groups and contributes to the production of endotoxin. Endotoxin promotes M1 macrophage infiltration in the ovaries, where they exhibit proinflammatory actions by secreting cytokines IL-6, IL-8, and TNFα. These cytokines then boost the activation of PFs by activating Signal Transducer and Activator of Transcription 3 (STAT3) signaling in follicles. Interestingly, transplantation of the HFD intestinal microflora to the ND mice partly replicates ovarian macrophage infiltration, proinflammation, and the overactivation of PFs. Conversely, transplanting the ND fecal microbiota to the HFD mice can alleviate ovarian inflammation and rescue the excessive consumption of PFs. Our findings uncover a novel and critical function of gut microbes in the process of PF overactivation under HFD conditions, and may provide a new theoretical basis for the microbial treatment of patients with premature ovarian insufficiency caused by HFD.}, }
@article {pmid35562867, year = {2022}, author = {Soriano, S and Curry, K and Wang, Q and Chow, E and Treangen, TJ and Villapol, S}, title = {Fecal Microbiota Transplantation Derived from Alzheimer's Disease Mice Worsens Brain Trauma Outcomes in Wild-Type Controls.}, journal = {International journal of molecular sciences}, volume = {23}, number = {9}, pages = {}, doi = {10.3390/ijms23094476}, pmid = {35562867}, issn = {1422-0067}, support = {R21NS106640/NH/NIH HHS/United States ; }, abstract = {Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration, both of which increase the risk and accelerate the progression of Alzheimer's disease (AD). The gut microbiome is an essential modulator of the immune system, impacting the brain. AD has been related with reduced diversity and alterations in the community composition of the gut microbiota. This study aimed to determine whether the gut microbiota from AD mice exacerbates neurological deficits after TBI in control mice. We prepared fecal microbiota transplants from 18 to 24 month old 3×Tg-AD (FMT-AD) and from healthy control (FMT-young) mice. FMTs were administered orally to young control C57BL/6 (wild-type, WT) mice after they underwent controlled cortical impact (CCI) injury, as a model of TBI. Then, we characterized the microbiota composition of the fecal samples by full-length 16S rRNA gene sequencing analysis. We collected the blood, brain, and gut tissues for protein and immunohistochemical analysis. Our results showed that FMT-AD administration stimulates a higher relative abundance of the genus Muribaculum and a decrease in Lactobacillus johnsonii compared to FMT-young in WT mice. Furthermore, WT mice exhibited larger lesion, increased activated microglia/macrophages, and reduced motor recovery after FMT-AD compared to FMT-young one day after TBI. In summary, we observed gut microbiota from AD mice to have a detrimental effect and aggravate the neuroinflammatory response and neurological outcomes after TBI in young WT mice.}, }
@article {pmid35561601, year = {2022}, author = {Wang, X and Wu, X and Cong, X and Ren, J and Li, J and Zhu, J and Dai, M and Hrabchenko, N and Du, Y and Qi, J}, title = {The functional role of fecal microbiota transplantation on Salmonella Enteritidis infection in chicks.}, journal = {Veterinary microbiology}, volume = {269}, number = {}, pages = {109449}, doi = {10.1016/j.vetmic.2022.109449}, pmid = {35561601}, issn = {1873-2542}, abstract = {The intestinal microbiota plays important roles in animal health and growth. We investigated the efficacy and mechanisms of fecal microbiota transplantation (FMT) from adult SPF chickens against Salmonella Enteritidis (SE) infection in chicks. We transplanted 160 recipient SPF chicks (1-day-old) that were randomly divided into four groups, Ca (challenge), Cb (non-challenge), Fa (FMT and challenge) and Fb (FMT without challenge). The experiment lasted 40 days. We found that FMT reduced mortality as well as liver inflammatory lesions, promoted weight gain, improved immunity, ameliorated the digestion and absorption ability and inhibited SE colonization in the liver of challenged chicks. 16S rRNA gene high-throughput sequencing indicated that SE challenge caused a significant increase in the relative abundance of Parasutterella in the cecal microbiota of the recipient chicks (P < 0.05). FMT led to the maturation of the intestinal flora of recipients and the relative abundance of the Bacteroides, Rikenellaceae_ RC9_ gut_ group, Prevotellaceae_ UCG_ 001, Prevotellaceae_ Ga6A1_ group and Parabacteroides was significantly increased (P < 0.05). FMT from adult SPF chickens regulated the intestinal microbiota of chicks and increased resistance to SE infection.}, }
@article {pmid35560552, year = {2022}, author = {Hermanson, JB and Fei, N and Miyoshi, S and Miyoshi, J and Hawkins, M and Xie, B and Sulakhe, D and Hart, J and Chang, EB and Leone, VA and Charlton, M}, title = {Dietary Cholesterol-Induced Gut Microbes Drive Nonalcoholic Fatty Liver Disease Pathogenesis in a Murine Model.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {36 Suppl 1}, number = {}, pages = {}, doi = {10.1096/fasebj.2022.36.S1.0R748}, pmid = {35560552}, issn = {1530-6860}, abstract = {Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are hepatic manifestations of metabolic syndrome and major indications for liver transplantation. Western diet contributes to disease pathogenesis, partially mediated through the gut microbiome, yet mechanisms remain elusive. Human epidemiological studies identified high dietary cholesterol intake as a NAFLD risk factor and it is essential to drive disease in murine models, yet little is known about its role in reshaping gut microbiota. Using the fast food (FF) diet murine model in germ-free (GF) mice completely devoid of all microbes and their conventionally-raised (control) counterparts harboring complex microbiomes, we hypothesized high dietary cholesterol-induced gut microbiota impact NAFLD onset, progression, and severity. Male C57Bl/6 age-matched GF and control mice were fed 1 of 4 semi-purified diets: low-fat (LF); high fat (HF); FF + 0.2% high cholesterol (FFHC); FF + 2% very high cholesterol (FFVHC) for 8 or 24 weeks. Fecal gut microbiota profiles were tracked over time via Illumina MiSeq 16S rRNA gene amplicon sequencing. Serum alanine transaminase (ALT) and lipopolysaccharide binding protein (LBP, an indicator of gut barrier function) were measured throughout the study. Livers were collected for histology and Illumina NovaSeq RNA-sequencing. Despite equal caloric intake between GF and controls across diets, significant weight gain and increased liver weight to body weight ratios (P<0.05) were observed only in control mice fed FF diets. GF mice were largely protected from disease, with no elevation in plasma ALT, LBP, or histology-based NAFLD activity score (NAS) regardless of treatment. Conversely, FFVHC control mice exhibited significantly elevated plasma ALT after 8 weeks on diet, which was exacerbated at 24 weeks relative to LF control and all GF groups. FF diets significantly increased (FFHC: P<0.05; FFVHC: P<0.01) plasma LBP after 24 weeks. Control mice fed FF diets exhibited severe steatosis, where FFVHC significantly increased NAS at 8 (P<0.05) and 24 (P<0.001) weeks relative to LF control and all GF groups. Microbiota profiling revealed no change in α-diversity regardless of diet in control mice. β-diversity analysis showed HF and FF diets, particularly FFVHC, rapidly shifted gut microbiota community membership after only 4 weeks, preceding disease onset and was further exacerbated over time. Liver RNA-seq revealed FFVHC diet in control, but not GF, mice significantly enriched genes involved in the KEGG pathway, "antigen processing and presentation" (Bonferroni P<0.001) relative to HF-fed counterparts at 24 weeks. Taken together, FF diet-induced shifts in gut microbes are both a prerequisite for and precede NAFLD/NASH disease onset, which is exacerbated by increased dietary cholesterol, driving liver inflammation. These data provide unique insights into how Western diet components impact host-microbe interactions in complex liver diseases, which may aid in identifying novel therapeutic interventions.}, }
@article {pmid35548572, year = {2022}, author = {Inczefi, O and Bacsur, P and Resál, T and Keresztes, C and Molnár, T}, title = {The Influence of Nutrition on Intestinal Permeability and the Microbiome in Health and Disease.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {718710}, doi = {10.3389/fnut.2022.718710}, pmid = {35548572}, issn = {2296-861X}, abstract = {The leakage of the intestinal barrier and the disruption of the gut microbiome are increasingly recognized as key factors in different pathophysiological conditions, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), chronic liver diseases, obesity, diabetes mellitus, types of cancer, and neuropsychiatric disorders. In this study, the mechanisms leading to dysbiosis and "leaky gut" are reviewed, and a short summary of the current knowledge regarding different diseases is provided. The simplest way to restore intestinal permeability and the microbiota could be ideal nutrition. Further therapeutic options are also available, such as the administration of probiotics or postbiotics or fecal microbiota transplantation.}, }
@article {pmid35548562, year = {2022}, author = {Lei, J and Dong, Y and Hou, Q and He, Y and Lai, Y and Liao, C and Kawamura, Y and Li, J and Zhang, B}, title = {Intestinal Microbiota Regulate Certain Meat Quality Parameters in Chicken.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {747705}, doi = {10.3389/fnut.2022.747705}, pmid = {35548562}, issn = {2296-861X}, abstract = {Growing evidence of intestinal microbiota-muscle axis provides a possibility to improve meat quality of broilers through regulating intestinal microbiota. Water-holding capacity is a crucial factor to evaluate the meat quality. High quality of water-holding capacity is usually described as a low drip-losing rate. This study aimed to explore the relationship between intestinal microbiota and water-holding capacity of muscle in broilers. According to our results, two native breeds of broilers (the Arbor Acres broilers and the Beijing-You broilers) exhibited remarkable differences in microbiota composition. However, the regular of gut bacteria compositions gradually became similar when the two breeds of broiler were raised in a same feeding environment. Therefore, this similar regular of intestinal microbiota induced similar water-holding capacity of the muscle from the two breeds. In subsequent fecal microbiota transplantation (FMT) experiments, the intestinal microbiota community of the Arbor Acres broilers was remodeling by oral gavage of bacterial suspension that was derived from the Beijing-You broilers. Then, not only body weight and abdominal fat rate were increased, but also drip loss of muscle was decreased in the Arbor Acres broilers. Additionally, muscle fiber diameter of biceps femoris muscle and expression of MyoD1 were notably enlarged. Muscle fiber diameter and related genes were deemed as important elements for water-holding capacity of muscle. Simultaneously, we screened typical intestinal bacteria in both the two native breeds of broilers by 16S rDNA sequencing. Lachnoclostridium was the only bacteria genus associated with drip-losing rate, meat fiber diameter, body weight, and abdominal fat rate.
Importance: Higher body weight and superior meat quality in livestock imply an adequate source of protein and substantial commercial value. Regulating the intestinal microbiota of broilers is a promising approach to optimize commercial phenotypes. Our results indicate that the intestinal microbiota profile could be reconstructed by external factors, leading to advantageous changes in muscle characteristics. The cecum microbiota of native broilers have the ability to improve certain meat quality and production performance. The population of Lachnoclostridium spp. could be used to regulate body weight and drip-losing rate in broilers, but more study is needed.}, }
@article {pmid35545183, year = {2022}, author = {Ouyang, ZR and Niu, XR and Wang, WG and Zhao, JH}, title = {The role of short-chain fatty acids in Clostridioides difficile infection: A review.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {102585}, doi = {10.1016/j.anaerobe.2022.102585}, pmid = {35545183}, issn = {1095-8274}, abstract = {Clostridioides difficile is a Gram-positive, obligate anaerobic, spore-producing intestinal opportunistic pathogen. CDI outbreaks in Europe and the Americas in recent years are a major health concern. Intestinal short-chain fatty acids (SCFAs) are an important energy source for colonic epithelial cells, and the roles of SCFAs in reducing intestinal inflammation, inhibiting intestinal tumours, and regulating gut microbial homeostasis are being actively researched. Furthermore, SCFAs attenuate CDI or directly inhibit C. difficile growth through different pathways in vivo and in vitro. This review assesses the role of SCFAs in CDI and discusses the potential use of these molecules as therapeutic targets for CDI.}, }
@article {pmid35539874, year = {2018}, author = {Diao, H and Yan, HL and Xiao, Y and Yu, B and Zheng, P and He, J and Yu, J and Mao, XB and Chen, DW}, title = {Modulation of intestine development by fecal microbiota transplantation in suckling pigs.}, journal = {RSC advances}, volume = {8}, number = {16}, pages = {8709-8720}, doi = {10.1039/c7ra11234c}, pmid = {35539874}, issn = {2046-2069}, abstract = {The present study was conducted to investigate the effects of early fecal microbiota transplantation on gut development in sucking piglets. A total of 24 3 day-old DLY sucking piglets (2.11 ± 0.15) kg were randomly divided into four groups (TMP, YMP, RMP and control group (CON)), which were transplanted with intact fecal microbiota of Tibetan pig (TP), Yorkshire pig (YP), Rongchang pig (RP), and without transplantation, respectively. The whole trial lasted for 56 d. The results are as follows: when compared with the YMP and RMP treatments, TMP and CON had a lower diarrhea index (P < 0.05), TMP and CON had higher GLP-2 and ANG4 mRNA abundances in the ileum (P < 0.05), and the TMP had a higher jejunal villus height: crypt depth and a higher colonic GLP-2 mRNA abundance (P < 0.05). Moreover, when compared with the YMP and RMP treatments, TMP had an enhanced DMT1 mRNA abundance in the duodenum (P < 0.05), TMP and CON had a greater lactase activity and a higher DMT1 mRNA abundance in the jejunum (P < 0.05), and CON had a higher γ-GT activity in the jejunum (P < 0.05). The jejunal Ca2+, Mg2+-ATPase activity in TMP was higher than that in CON, and the jejunal Na+, K+-ATPase activity in TMP was higher than that in the other three treatments (P < 0.05). Besides, when compared with the YMP and RMP treatments, TMP had a lower MDA content and a higher MUC1 mRNA abundance in the jejunum (P < 0.05); CON had a higher SOD activity in the jejunum (P < 0.05), whereas TMP and CON had a higher butyric acid concentration in the colon and a lower LPS content in the serum (P < 0.05). Finally, when compared with the TMP treatment, the other three treatments had an enhanced IL-10 mRNA abundance in the colon (P < 0.05), YMP and CON had higher counts of Escherichia coli in the colonic digesta (P < 0.05), and the CON had lower counts of Lactobacillus spp in the cecal and colonic digesta (P < 0.05). These data indicated that early transplantation of the fecal microbiota from the Yorkshire pigs and Rongchang pigs to DLY suckling piglets would destroy the gut microbiota balance and thus damage intestinal health.}, }
@article {pmid35538082, year = {2022}, author = {Shin, J and Noh, JR and Choe, D and Lee, N and Song, Y and Cho, S and Kang, EJ and Go, MJ and Ha, SK and Kim, JH and Kim, YH and Kim, KS and Kim, BC and Lee, CH and Cho, BK}, title = {Comprehensive 16S rRNA and metagenomic data from the gut microbiome of aging and rejuvenation mouse models.}, journal = {Scientific data}, volume = {9}, number = {1}, pages = {197}, pmid = {35538082}, issn = {2052-4463}, support = {2019M3A9F3065867//National Research Foundation of Korea (NRF)/ ; 2018M3A9H3024759//National Research Foundation of Korea (NRF)/ ; }, abstract = {The gut microbiota is associated with the health and longevity of the host. A few methods, such as fecal microbiota transplantation and oral administration of probiotics, have been applied to alter the gut microbiome and promote healthy aging. The changes in host microbiomes still remain poorly understood. Here, we characterized both the changes in gut microbial communities and their functional potential derived from colon samples in mouse models during aging. We achieved this through four procedures including co-housing, serum injection, parabiosis, and oral administration of Akkermansia muciniphila as probiotics using bacterial 16 S rRNA sequencing and shotgun metagenomic sequencing. The dataset comprised 16 S rRNA sequencing (36,249,200 paired-end reads, 107 sequencing data) and metagenomic sequencing data (307,194,369 paired-end reads, 109 sequencing data), characterizing the taxonomy of bacterial communities and their functional potential during aging and rejuvenation. The generated data expand the resources of the gut microbiome related to aging and rejuvenation and provide a useful dataset for research on developing therapeutic strategies to achieve healthy active aging.}, }
@article {pmid35535879, year = {2022}, author = {Alsegiani, AS and Shah, ZA}, title = {The influence of gut microbiota alteration on age-related neuroinflammation and cognitive decline.}, journal = {Neural regeneration research}, volume = {17}, number = {11}, pages = {2407-2412}, doi = {10.4103/1673-5374.335837}, pmid = {35535879}, issn = {1673-5374}, abstract = {Recent emerging research on intestinal microbiota and its contribution to the central nervous system during health and disease has attracted significant attention. Age-related intestinal microbiota changes initiate brain aging and age-related neurodegenerative disorders. Aging is one of the critical predisposing risk factors for the development of neurodegenerative diseases. Maintaining a healthy gut microbiota is essential for a healthy body and aging, but dysbiosis could initiate many chronic diseases. Understanding the underlying mechanisms of gut microbiota alterations/dysbiosis will help identify biomarkers for aging-related chronic conditions. This review summarizes recent advances in microbiota-neurodegenerative disease research and will enhance our understanding of gut microbiota dysbiosis and its effects on brain aging.}, }
@article {pmid35535069, year = {2022}, author = {Philips, CA and Augustine, P}, title = {Gut Barrier and Microbiota in Cirrhosis.}, journal = {Journal of clinical and experimental hepatology}, volume = {12}, number = {2}, pages = {625-638}, doi = {10.1016/j.jceh.2021.08.027}, pmid = {35535069}, issn = {0973-6883}, abstract = {Gut microbiota and their homeostatic functions are central to the maintenance of the intestinal mucosal barrier. The gut barrier functions as a structural, biological, and immunological barrier, preventing local and systemic invasion and inflammation of pathogenic taxa, resulting in the propagation or causation of organ-specific (liver disease) or systemic diseases (sepsis) in the host. In health, commensal bacteria are involved in regulating pathogenic bacteria, sinister bacterial products, and antigens; and help control and kill pathogenic organisms by secreting antimicrobial metabolites. Gut microbiota also participates in the extraction, synthesis, and absorption of nutrient metabolites, maintains intestinal epithelial integrity and regulates the development, homeostasis, and function of innate and adaptive immune cells. Cirrhosis is associated with local and systemic immune, vascular, and inflammatory changes directly or indirectly linked to perturbations in quality and quantity of intestinal microbiota and intestinal mucosal integrity. Dysbiosis and gut barrier dysfunction are directly involved in the pathogenesis of compensated cirrhosis and the type and severity of complications in decompensated cirrhosis, such as bacterial infections, encephalopathy, extrahepatic organ failure, and progression to acute on chronic liver failure. This paper reviews the normal gut barrier, gut barrier dysfunction, and dysbiosis-associated clinical events in patients with cirrhosis. The role of dietary interventions, antibiotics, prebiotics, probiotics, synbiotics, and healthy donor fecal microbiota transplantation (FMT) to modulate the gut microbiota for improving patient outcomes is further discussed.}, }
@article {pmid35530905, year = {2022}, author = {Alabdaljabar, MS and Aslam, HM and Veeraballi, S and Faizee, FA and Husain, BH and Iqbal, SM and Hashmi, SK}, title = {Restoration of the Original Inhabitants: A Systematic Review on Fecal Microbiota Transplantation for Graft-Versus-Host Disease.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e23873}, doi = {10.7759/cureus.23873}, pmid = {35530905}, issn = {2168-8184}, abstract = {A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD, we conducted a systemic literature search using multiple electronic databases. Upon pooling of data, 79 patients from six studies and five case reports were included. Complete remission (CR) occurred in 55.9% of patients, and partial remission (PR) occurred in 26.5% of patients (82.4% overall response rate). A limited number of patients had treatment-related mortality (TRM), while few showed mild gastrointestinal (GI)-related and non-GI adverse effects. None of the studies directly examined the role of FMT in the prevention of GVHD. In conclusion, FMT seems to be a safe and effective strategy for the management of GVHD based on the current evidence. Due to the small number of patients evaluated and the absence of randomized data, one cannot portray FMT as a standard of care yet; however, the low toxicity along with the clinical improvement justifies this modality to be tested in a randomized fashion.}, }
@article {pmid35530507, year = {2022}, author = {Lai, Z and Chen, Z and Zhang, A and Niu, Z and Cheng, M and Huo, C and Xu, J}, title = {The Gut Microbiota in Liver Transplantation Recipients During the Perioperative Period.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {854017}, doi = {10.3389/fphys.2022.854017}, pmid = {35530507}, issn = {1664-042X}, abstract = {Background: Chronic liver disease is a global problem, and an increasing number of patients receive a liver transplant yearly. The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients during the perioperative. Methods: We studied gut fecal microbial community signatures in 37 Chinese adults using 16S rRNA sequencing targeting V3-V4 hypervariable regions, with a total of 69 fecal samples. We analyzed the Alpha and Beta diversities of various groups. Then we compared the abundance of bacteria in groups at the phylum, family, and genus levels. Results: The healthy gut microbiota predominantly consisted of the phyla Firmicutes and Bacteroidestes, followed by Proteobacteria and Actinobacteria. Compared with healthy people, due to the dominant bacteria in patients with chronic liver disease losing their advantages in the gut, the antagonistic effect on the inferior bacteria was reduced. The inferior bacteria multiplied in large numbers during this process. Some of these significant changes were observed in bacterial species belonging to Enterococcus, Klebsiella, and Enterobacter, which increased in patients' intestines. There were low abundances of signature genes such as Bacteroides, Prevotella, and Ruminococcus. Blautia and Bifidobacterium (considered probiotics) almost disappeared after liver transplantation. Conclusion: There is an altered microbial composition in liver transplantation patients and a distinct signature of microbiota associated with the perioperative period.}, }
@article {pmid35528013, year = {2022}, author = {Liang, F and Lu, X and Deng, Z and Zhong, HJ and Zhang, W and Li, Q and Zhou, HH and Liou, YL and He, XX}, title = {Effect of Washed Microbiota Transplantation on Patients With Dyslipidemia in South China.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {827107}, doi = {10.3389/fendo.2022.827107}, pmid = {35528013}, issn = {1664-2392}, abstract = {Background and Aims: Although the manual crude fecal microbiota transplantation (FMT) reduces blood lipids in animal models of hyperlipidemia, its clinical effect on blood lipid metabolism in patients with hyperlipidemia and hypolipidemia remains unclear, especially in the Chinese population. It was reported that washed microbiota transplantation (WMT) was safer, more precise, and more quality-controllable than the crude FMT by manual. This study aimed to investigate the feasibility and effectiveness of WMT on lipid metabolism in the Chinese population.
Methods: Clinical data of patients with various indications who received WMT for 1-3 treatment procedures were collected. Changes in blood lipids before and after WMT, namely, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), liver fat attenuation, and liver stiffness measurement, were compared.
Results: A total of 177 patients (40 cases of hyperlipidemia, 87 cases with normal blood lipids, and 50 cases of hypolipidemia) were enrolled in the First Affiliated Hospital of Guangdong Pharmaceutical University. WMT has a significant therapeutic effect in reducing blood lipid levels (TC and TG) in the short- and medium term in patients with hyperlipidemia (p <0.05). Hyper blood lipid decreased to normal in the short-term (35.14%; p <0.001), and LDL-C changed to normal in the medium term (33.33%; p = 0.013). In the hypolipidemia group, 36.36% and 47.06% changed to normal in the short-term (p = 0.006) and medium term (p = 0.005) of therapeutic effects based on blood lipid levels. In the normal blood lipid group and the low-risk group of atherosclerotic cardiovascular disease (ASCVD), the change was not statistically significant, indicating that WMT does not increase the risk of blood lipid and ASCVD in the long-term.
Conclusions: WMT treatment changes blood lipids in patients with hyperlipidemia and hypolipidemia without serious adverse events, with no risk for increasing blood lipids and ASCVD in the long-term. There were significant decreased TC, TG, and LDL-C levels in the medium term of WMT treatment for hyperlipidemia. Therefore, the regulation of gut microbiota by WMT may indicate a new clinical method for the treatment of dyslipidemia.}, }
@article {pmid35526726, year = {2022}, author = {Kinoshita, Y and Niwa, H and Uchida-Fujii, E and Nukada, T and Ueno, T}, title = {Simultaneous daily fecal microbiota transplantation fails to prevent metronidazole-induced dysbiosis of equine gut microbiota.}, journal = {Journal of equine veterinary science}, volume = {}, number = {}, pages = {104004}, doi = {10.1016/j.jevs.2022.104004}, pmid = {35526726}, issn = {0737-0806}, abstract = {Antimicrobial administration can lead to imbalances of gastrointestinal microbiota, called dysbiosis. Dysbiosis sometimes results in diarrhea and enteritis in horses. Fecal microbiota transplantation (FMT) is used to treat affected horses, but whether it is effective as a prophylactic approach for dysbiosis in horses receiving antimicrobials remains unknown. The aim of this study was to assess the efficacy of simultaneous FMT against metronidazole-induced dysbiosis in horses. Changes in the ratios of bacterial families, determined by metagenomic analysis, were similar between the metronidazole-treated group and the simultaneous metronidazole- and FMT-treated group, notably in the Clostridiaceae, Ruminococcaceae, and Enterobacteriaceae. Differences in fecal bacterial compositions were due mainly to metronidazole administration (P = 0.0003), but not to FMT (P = 0.3136). Simultaneous FMT at 500 g of donor feces in 1 L of suspension once a day did not inhibit metronidazole-induced dysbiosis. The results show that the FMT protocol needs to be improved to prevent metronidazole-induced gut dysbiosis in horses.}, }
@article {pmid35332832, year = {2022}, author = {Crits-Christoph, A and Hallowell, HA and Koutouvalis, K and Suez, J}, title = {Good microbes, bad genes? The dissemination of antimicrobial resistance in the human microbiome.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2055944}, pmid = {35332832}, issn = {1949-0984}, support = {DP5 OD029603/OD/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Drug Resistance, Bacterial/genetics ; *Gastrointestinal Microbiome/genetics ; Genes, Bacterial ; Humans ; Metagenomics ; *Microbiota/genetics ; }, abstract = {A global rise in antimicrobial resistance among pathogenic bacteria has proved to be a major public health threat, with the rate of multidrug-resistant bacterial infections increasing over time. The gut microbiome has been studied as a reservoir of antibiotic resistance genes (ARGs) that can be transferred to bacterial pathogens via horizontal gene transfer (HGT) of conjugative plasmids and mobile genetic elements (the gut resistome). Advances in metagenomic sequencing have facilitated the identification of resistome modulators, including live microbial therapeutics such as probiotics and fecal microbiome transplantation that can either expand or reduce the abundances of ARG-carrying bacteria in the gut. While many different gut microbes encode for ARGs, they are not uniformly distributed across, or transmitted by, various members of the microbiome, and not all are of equal clinical relevance. Both experimental and theoretical approaches in microbial ecology have been applied to understand differing frequencies of ARG horizontal transfer between commensal microbes as well as between commensals and pathogens. In this commentary, we assess the evidence for the role of commensal gut microbes in encoding antimicrobial resistance genes, the degree to which they are shared both with other commensals and with pathogens, and the host and environmental factors that can impact resistome dynamics. We further discuss novel sequencing-based approaches for identifying ARGs and predicting future transfer events of clinically relevant ARGs from commensals to pathogens.}, }
@article {pmid33785557, year = {2022}, author = {Ng, SC and Xu, Z and Mak, JWY and Yang, K and Liu, Q and Zuo, T and Tang, W and Lau, L and Lui, RN and Wong, SH and Tse, YK and Li, AYL and Cheung, K and Ching, JYL and Wong, VWS and Kong, APS and Ma, RCW and Chow, EYK and Wong, SKH and Ho, ICH and Chan, PKS and Chan, FKL}, title = {Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: a 24-week, double-blind, randomised controlled trial.}, journal = {Gut}, volume = {71}, number = {4}, pages = {716-723}, doi = {10.1136/gutjnl-2020-323617}, pmid = {33785557}, issn = {1468-3288}, mesh = {*Diabetes Mellitus, Type 2/complications/therapy ; Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Obesity/complications/microbiology/therapy ; Treatment Outcome ; }, abstract = {OBJECTIVE: The impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).
DESIGN: In this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24.
RESULTS: Proportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in Bifidobacterium and Lactobacillus compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05).
CONCLUSION: Repeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients' microbiota and improvement in lipid profile and liver stiffness.
TRIAL REGISTRATION NUMBER: NCT03127696.}, }
@article {pmid35525320, year = {2022}, author = {Ianiro, G}, title = {An artificial microbiome consortium prevents recurrence of C. difficile infection: paving the way for fecal microbiota transplantation 2.0.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2022.05.002}, pmid = {35525320}, issn = {1528-0012}, }
@article {pmid35517805, year = {2022}, author = {Liu, D and Zhao, R and Wu, Y and Wang, Y and Yang, R and Ke, X}, title = {Variation in the Efficacy of Anti-Ulcerative Colitis Treatments Reveals the Conflict Between Precipitating Compatibility of Traditional Chinese Medicine and Modern Technology: A Case of Scutellaria-Coptis.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {819851}, doi = {10.3389/fphar.2022.819851}, pmid = {35517805}, issn = {1663-9812}, abstract = {Scutellariae and Coptidis compose a classical drug pair applied in clinical practice to dispel heat, dryness, and dampness, and they are also precipitation compatible drug pairs. With modern technology, Scutellaria-Coptis is mostly prepared by decocting its components separately, while in the traditional method, it is predominantly prepared as a combined decoction. The present study investigated the effects and mechanisms of separate and combined application of Scutellaria-Coptis decoction on ulcerative colitis (UC) in mice induced by the administration of dextran sulfate sodium (DSS). Changes in body weight, colon length, and Disease Activity Index scores were also evaluated. Hematoxylin and eosin staining and other methods were used to evaluate the overall condition of animals in each group. Intestinal microflora was analyzed using 16S rRNA sequencing, while colon inflammation and antioxidant capacity were evaluated based on the levels of interleukin-6 (IL-6), IL-10, IL-1β, tumor necrosis factor-α, superoxide dismutase, malondialdehyde, and reduced glutathione. The results revealed that Scutellaria-Coptis significantly relieved colon inflammation in mice, and the combined decoction of Scutellaria-Coptis exerted a significant effect on UC. Notably, the protective effect of Scutellaria-Coptis against colon inflammation was weakened when the antibiotic mixture was partially consumed by the gut microbiota. The results of 16S rRNA sequencing showed that the group treated with combined decoction of Scutellaria-Coptis exhibited a higher intestinal microbial diversity and intestinal flora composition than the separated decoction group. Treatment of mice with UC by administering Scutellaria-Coptis decoction through intestinal flora removal (ABX) and fecal microbial transplantation (FMT) was closely associated with intestinal flora composition. In conclusion, Scutellaria-Coptis can relieve UC with an excellent effect especially when taken as a combined decoction, alleviating colon inflammation incurred by intestinal microbes to a certain extent.}, }
@article {pmid35510325, year = {2022}, author = {Cheng, F and Huang, Z and Li, Z and Wei, W}, title = {Efficacy and safety of fecal microbiota transplant for recurrent Clostridium difficile infection in inflammatory bowel disease patients: a systematic review and meta-analysis.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {}, number = {}, pages = {}, doi = {10.17235/reed.2022.8814/2022}, pmid = {35510325}, issn = {1130-0108}, abstract = {OBJECTIVES: The objective of this systematic review and meta-analysis was to evaluate the outcomes of fecal microbiota transplantation (FMT) therapy for recurrent Clostridium difficile infection (C) among inflammatory bowel disease (IBD) patients.
METHODS: Electronic databases were searched for studies that reported efficacy and/or safety of FMT therapy for recurrent CDI among IBD. We used the meta-prop command of the meta package in R to assess the efficacy and safety. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes.
RESULTS: 11 trials were included in our study. Pooled analysis showed that the initial cure rate of recurrent CDI among IBD patients was 80% (95% CI 0.76, 0.84), and the overall cure rate after two or more FMT procedures was 90% (95% CI 0.84, 0.94). The recurrence rate post FMT therapy was 25% (95% CI: 0.20, 0.32). Sub-analyses suggested that the initial cure rate of CDI in ulcerative colitis (UC) patients was higher than that in Crohn's disease (CD) patients (85% vs. 79%), with no statistically significant differences (P >0.05). No serious adverse events were noted in any of the patients post-FMT.
CONCLUSIONS: FMT is an effective and safe treatment for recurrent CDI in patients with IBD. FMT should be considered early in cases of recurrent or refractory CDI. Multiple FMT procedures can improve the cure rate of CDI.}, }
@article {pmid35506083, year = {2022}, author = {Oliveira, AC and Yang, T and Li, J and Sharma, RK and Karas, MK and Bryant, AJ and de Kloet, AD and Krause, EG and Joe, B and Richards, EM and Raizada, MK}, title = {Fecal matter transplant from Ace2 overexpressing mice counteracts chronic hypoxia-induced pulmonary hypertension.}, journal = {Pulmonary circulation}, volume = {12}, number = {1}, pages = {e12015}, doi = {10.1002/pul2.12015}, pmid = {35506083}, issn = {2045-8932}, abstract = {Recent evidence suggests pulmonary hypertension (PH), a disease of the pulmonary vasculature actually has multiorgan pathophysiology and perhaps etiology. Herein, we demonstrated that fecal matter transplantation from angiotensin-converting enzyme 2 overexpressing mice counteracted the effects of chronic hypoxia to prevent pulmonary hypertension, neuroinflammation, and gut dysbiosis in wild type recipients.}, }
@article {pmid35501923, year = {2022}, author = {Parker, A and Romano, S and Ansorge, R and Aboelnour, A and Le Gall, G and Savva, GM and Pontifex, MG and Telatin, A and Baker, D and Jones, E and Vauzour, D and Rudder, S and Blackshaw, LA and Jeffery, G and Carding, SR}, title = {Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {68}, pmid = {35501923}, issn = {2049-2618}, abstract = {BACKGROUND: Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina.
METHODS: Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing.
RESULTS: We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota.
CONCLUSIONS: These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut-brain and gut-retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life. Video abstract.}, }
@article {pmid35493741, year = {2022}, author = {Xing, J and Liao, Y and Zhang, H and Zhang, W and Zhang, Z and Zhang, J and Wang, D and Tang, D}, title = {Impacts of MicroRNAs Induced by the Gut Microbiome on Regulating the Development of Colorectal Cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {804689}, pmid = {35493741}, issn = {2235-2988}, mesh = {*Colorectal Neoplasms/microbiology ; Faecalibacterium prausnitzii ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; *MicroRNAs/genetics ; }, abstract = {Although a dysfunctional gut microbiome is strongly linked to colorectal cancer (CRC), our knowledge of the mediators between CRC and the microbiome is limited. MicroRNAs (miRNAs) affect critical cellular processes, such as apoptosis, proliferation, and differentiation, and contribute to the regulation of CRC progression. Increasingly, studies found that miRNAs can significantly mediate bidirectional interactions between the host and the microbiome. Notably, miRNA expression is regulated by the gut microbiome, which subsequently affects the host transcriptome, thereby influencing the development of CRC. This study typically focuses on the specific functions of the microbiome in CRC and their effect on CRC-related miRNA production and reviews the role of several bacteria on miRNA, including Fusobacterium nucleatum, Escherichia coli, enterotoxigenic Bacteroides fragilis, and Faecalibacterium prausnitzii. Based on the important roles of miRNAs and the gut microbiome in CRC, strategies for modulating miRNA expression and regulating the gut microbiome composition need to be applied, such as bioactive dietary components and fecal microorganism transplantation.}, }
@article {pmid35500802, year = {2022}, author = {Li, X and Zhao, W and Xiao, M and Yu, L and Chen, Q and Hu, X and Zhao, Y and Xiong, L and Chen, X and Wang, X and Ba, Y and Guo, Q and Wu, X}, title = {Penthorum chinense Pursh. extract attenuates non-alcholic fatty liver disease by regulating gut microbiota and bile acid metabolism in mice.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {115333}, doi = {10.1016/j.jep.2022.115333}, pmid = {35500802}, issn = {1872-7573}, abstract = {Penthorum chinense Pursh. (PCP) is commonly used as a Miao ethno-medicine and health food for liver protection in China. Gansukeli (WS3-B-2526-97) is made from the extract of PCP (PCPE) for the treatment of viral hepatitis. In recent years, PCPE has been reported in the treatment of non-alcoholic fatty liver disease (NAFLD), however its potential mechanism is not fully elucidated.
AIM OF THE STUDY: To investigate the ameliorating effect of PCPE on high-fat diet (HFD)-induced NAFLD mice and demonstrate whether its protective effect is gut microbiota dependent and associated with bile acid (BA) metabolism.
MATERIALS AND METHODS: The alleviating effect of PCPE on NAFLD was conducted on male C57BL/6J mice fed an HFD for 16 weeks, and this effect associated with gut microbiota dependent was demonstrated by pseudo-germfree mice treated with antibiotics and fecal microbiota transplantation (FMT). The composition of the gut microbiota in the cecum contents was analyzed by 16S rRNA sequencing, and the levels of BAs in liver and fecal samples were determined by UPLC/MS-MS.
RESULTS: The results showed that administration of PCPE for 8 weeks could potently ameliorate HFD-induced NAFLD and alleviate dyslipidemia and insulin resistance. Moreover, PCPE treatment alleviated gut dysbiosis, especially reducing the relative abundance of bile salt hydrolase (BSH)-producing bacteria. Furthermore, PCPE significantly increased the levels of taurine-conjugated BAs in feces, such as tauro-β-muricholic acid (T-βMCA), tauroursodesoxycholic acid (TUDCA), and taurochenodeoxycholic acid (TCDCA), and increased hepatic chenodeoxycholic acid (CDCA). The protein and mRNA expression of farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) were decreased in intestine, increased taurine-conjugated BAs inhibited the intestinal signaling pathway, which was associated with increased genes expression of enzymes in the alternative BA synthesis pathway that reduced the levels of cholesterol. The increased CDCA produced via the alternative BA synthesis pathway promoted hepatic FXR activation and BA excretion.
CONCLUSION: Our study is the first time to demonstrate that PCPE could ameliorate NAFLD in HFD-induced mice by regulating the gut microbiota and BA metabolism, and from a novel view, to understand the mechanism of PCPE in NAFLD.}, }
@article {pmid35499059, year = {2022}, author = {Shen, Q and Huang, Z and Yao, J and Jin, Y}, title = {Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease.}, journal = {Journal of advanced research}, volume = {37}, number = {}, pages = {221-233}, doi = {10.1016/j.jare.2021.07.002}, pmid = {35499059}, issn = {2090-1224}, abstract = {Background: The intestinal tract is a complicated ecosystem with dynamic homeostasis via interaction of intestine and microbiota. Inflammatory bowel disease (IBD) is chronic intestinal inflammation involving dysbiosis of intestinal microenvironment. Extracellular vesicles (EVs), as vital characteristics of cell-cell and cell-organism communication, contribute to homeostasis in intestine. Recently, EVs showed excellent potential for clinical applications in disease diagnoses and therapies.
Aim of Review: Our current review discusses the modulatory functions of EVs derived from different sources in intestine, especially their effects and applications in IBD clinical therapy. EV-mediated interaction systems between host intestine and microbiota were established to describe possible mechanisms of IBD pathogenesis and its cure.
EVs are excellent vehicles for delivering molecules containing genetic information to recipient cells. Multiple pieces of evidence have illustrated that EVs participate the interaction between host and microbiota in intestinal microenvironment. In inflammatory intestine with dysbiosis of microbiota, EVs as regulators target promoting immune response and microbial reconstruction. EVs-based immunotherapy could be a promising therapeutic approach for the treatment of IBD in the near future.}, }
@article {pmid35499044, year = {2022}, author = {Wu, C and Zhao, Y and Zhang, Y and Yang, Y and Su, W and Yang, Y and Sun, L and Zhang, F and Yu, J and Wang, Y and Guo, P and Zhu, B and Wu, S}, title = {Gut microbiota specifically mediates the anti-hypercholesterolemic effect of berberine (BBR) and facilitates to predict BBR's cholesterol-decreasing efficacy in patients.}, journal = {Journal of advanced research}, volume = {37}, number = {}, pages = {197-208}, doi = {10.1016/j.jare.2021.07.011}, pmid = {35499044}, issn = {2090-1224}, abstract = {Introduction: Gut microbiota has been implicated in the pharmacological activities of many natural products. As an effective hypolipidemic agent, berberine (BBR)'s clinical application is greatly impeded by the obvious inter-individual response variation. To date, little evidence exists on the causality between gut microbes and its therapeutic effects, and the linkage of bacteria alterations to the inter-individual response variation.
Objectives: This study aims to confirm the causal role of the gut microbiota in BBR's anti-hyperlipidemic effect and identify key bacteria that can predict its effectiveness.
Methods: The correlation between gut microbiota and BBR's inter-individual response variation was studied in hyperlipidemic patients. The causal role of gut microbes in BBR's anti-hyperlipidemic effects was subsequently assessed by altered administration routes, co-treatment with antibiotics, fecal microbiota transplantation, and metagenomic analysis.
Results: Three-month clinical study showed that BBR was effectively to decrease serum lipids but displayed an obvious response variation. The cholesterol-lowering but not triglyceride-decreasing effect of BBR was closely related to its modulation on gut microbiota. Interestingly, the baseline levels of Alistipes and Blautia could accurately predict its anti-hypercholesterolemic efficiency in the following treatment. Causality experiments in mice further confirmed that the gut microbiome is both necessary and sufficient to mediate the lipid-lowering effect of BBR. The absence of Blautia substantially abolished BBR's cholesterol-decreasing efficacy.
Conclusion: The gut microbiota is necessary and sufficient for BBR's hyperlipidemia-ameliorating effect. The baseline composition of gut microbes can be an effective predictor for its pharmacotherapeutic efficacy, providing a novel way to achieve personalized therapy.}, }
@article {pmid35498721, year = {2022}, author = {Liu, T and Guo, Y and Lu, C and Cai, C and Gao, P and Cao, G and Li, B and Guo, X and Yang, Y}, title = {Effect of Different Pig Fecal Microbiota Transplantation on Mice Intestinal Function and Microbiota Changes During Cold Exposure.}, journal = {Frontiers in veterinary science}, volume = {9}, number = {}, pages = {805815}, doi = {10.3389/fvets.2022.805815}, pmid = {35498721}, issn = {2297-1769}, abstract = {Cold stress influences intestinal processes, causing physiological and immunological responses in animals. Intestinal microbiota participates in maintaining the stability of the intestinal environment. However, phenotypic characteristics and the effects of porcine microbiota changes under cold conditions remain poorly understood. Here, the fecal microbiota of cold tolerant breed (Mashen) and cold sensitive breed (Duroc-Landrace-Yorkshire) was transferred to germ-free mice, respectively. After a cold exposure (4°C) for 21 days, intestinal function and microbe changes of mice were explored. The results showed that Mashen pigs microbiota transplantation made the body temperature of the mice stable, in which the fat weight and expression of uncoupling protein 1 (UCP1), carnitine palmitoyltransferase 1B (Cpt1b), and Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) were significantly higher (P < 0.05) than those of the control group. The results of intestinal structure and expression of serum inflammatory factors showed that fecal microbiota transplantation (FMT) mice have more intact intestinal structure and high expression of proinflammatory factor such as interleukin-4 (IL-4). The study of mice fecal microbiome characterized via 16S rRNA sequencing found that pig microbiota transplantation changed the abundance of Firmicutes. In addition, it identified discriminative features of Firmicutes in the microbiota between two breeds of pig, in which Clostridiaceae were enriched in the microbiota community of Mashen pig and Coriobacteriales were significantly (P < 0.05) enriched in the Duroc-Landrace-Yorkshire pig microbiota transplantation group based on linear discriminant analysis effect size (LEfSe) analysis. Finally, we found that the content of propionic acid and butyric acid in rectal contents significantly changed and the abundances of Clostridium and Lachnospira showed significant correlations with changes in short-chain fatty acids. The results suggest that pig fecal microbiota transplantation can alleviate the changes in physiological and biochemical indicators in mice caused by cold exposure. Mice have gut microbes altered and improved gut barrier function via fecal microbiota transplantation in pigs.}, }
@article {pmid35496818, year = {2021}, author = {Wang, Q and Wang, X and Lv, Y and Yang, C and Zhou, C and Wang, L}, title = {Changes in Rats' Gut Microbiota Composition Caused by Induced Chronic Myocardial Infarction Lead to Depression-Like Behavior.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {641084}, doi = {10.3389/fmicb.2021.641084}, pmid = {35496818}, issn = {1664-302X}, abstract = {Depression is common among patients who have chronic myocardial infarction (CMI). Despite their frequency, depression and CMI are bidirectional related conditions, each is a risk for the other, and they often co-exist, suggesting shared or interacting pathomechanisms. Accumulating data revealed the effects of gut microbiota in terms of regulating depression via the gut-brain axis. Thus, we investigated the role of gut microbial dysbiosis in CMI-induced depression-like behavior. Hierarchical cluster analysis of sucrose preference test (SPT) results was adopted to classify the CMI rats into depression-like behavior (CMI + Dep) or non-depression-like behavior (CMI + Non-Dep) phenotypes. First, 16S ribosomal RNA sequencing analysis showed both β-diversity and relative abundance of several gut bacteria significantly differed between the CMI + Dep and CMI + Non-Dep rats. Next, transplantation of fecal microbiota from CMI + Dep rats visibly altered the relative abundance of gut microbiota and also induced depression-like behavior in the antibiotics-treated pseudo-germ-free rats. In conclusion, these findings suggested that dysbiosis in gut microbial composition contributed to the onset of CMI-induced depression-like behavior and that exogenous regulation of gut microbiota composition could be a potential therapeutic strategy for CMI and related depression-like behavior.}, }
@article {pmid35495114, year = {2022}, author = {Xu, P and Lv, T and Dong, S and Cui, Z and Luo, X and Jia, B and Jeon, CO and Zhang, J}, title = {Association between intestinal microbiome and inflammatory bowel disease: Insights from bibliometric analysis.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {1716-1725}, doi = {10.1016/j.csbj.2022.04.006}, pmid = {35495114}, issn = {2001-0370}, abstract = {The gut microbiome is highly linked to inflammatory bowel disease (IBD). A total of 3890 publications related to the two terms from 2000 to 2020 were extracted from the Web of Science Core Collection to study the association from a bibliometric perspective. Publications on this topic have grown rapidly since 2008. The United States and Harvard University are the country and institution with the largest number of publications, respectively. Inflammatory Bowel Diseases is the most productive journal with 211 published articles. The most influential journal in this field is Gut with 13,359 citations. The co-citation analysis of references showed that the IBD-related topics with the highest focus are "gut microbiota," "metagenomics," "bacterial community," "fecal microbiota transplantation," "probiotics," and "colitis-associated colorectal cancer." Keyword cluster and keyword burst analyses showed that "gut microbiota," "metagenomics," and "fecal microbiota transplantation" are currently the most researched topics in the field of IBD. The literature in this field is mainly distributed between alterations of the intestinal microbiota, microbial metabolites, and related host signaling pathways. Probiotic treatment also frequently appears in literature. This bibliometric analysis can guide future research and promote the development of the field of gut microbiome and IBD.}, }
@article {pmid33687943, year = {2022}, author = {Lai, HC and Lin, TL and Chen, TW and Kuo, YL and Chang, CJ and Wu, TR and Shu, CC and Tsai, YH and Swift, S and Lu, CC}, title = {Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide.}, journal = {Gut}, volume = {71}, number = {2}, pages = {309-321}, doi = {10.1136/gutjnl-2020-322599}, pmid = {33687943}, issn = {1468-3288}, mesh = {Animals ; Bacteroidetes/*isolation & purification ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Lipopolysaccharides/metabolism ; Mice ; Mice, Inbred C57BL ; Pulmonary Disease, Chronic Obstructive/*etiology/metabolism/pathology ; Smoking ; }, abstract = {OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.
DESIGN: A murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.
RESULTS: Gut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.
CONCLUSION: The gut microbiota-lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.}, }
@article {pmid35489181, year = {2022}, author = {Ezquer, F and Quintanilla, ME and Morales, P and Santapau, D and Munita, JM and Moya-Flores, F and Ezquer, M and Herrera-Marschitz, M and Israel, Y}, title = {A dual treatment blocks alcohol binge-drinking relapse: Microbiota as a new player.}, journal = {Drug and alcohol dependence}, volume = {236}, number = {}, pages = {109466}, doi = {10.1016/j.drugalcdep.2022.109466}, pmid = {35489181}, issn = {1879-0046}, abstract = {RATIONALE: Gut microbiota communicates information to the brain. Some animals are born with a gut microbiota that predisposes to high alcohol consumption, and transplantation of fecal material from alcoholics to mice increases animal preference for ethanol. Alcohol-use-disorders are chronic conditions where relapse is the hallmark. A predictive animal model of relapse is the "alcohol deprivation effect" where ethanol re-access is allowed following chronic alcohol intake and a long alcohol deprivation. The present study evaluates the effect of gut microbiota modification on relapse, as an adjunct to N-acetylcysteine + Acetylsalicylic acid administration, which inhibits the alcohol-induced hyper-glutamatergic condition.
METHODS: Rats bred as heavy alcohol consumers (UChB) were allowed ethanol intake for one month, were deprived of alcohol for two-weeks and subsequently offered re-access to ethanol. Prior to ethanol re-access animals received orally either (i) vehicle-control, (ii) Lactobacillus-rhamnosus-GG after antibiotic treatment (LGG); (iii) N-acetylcysteine+Acetylsalicylic acid (NAC/ASA) or (iv) both treatments: LGG+ (NAC/ASA).
RESULTS: Marked binge drinking (1.75 g ethanol/kg in 60 min) and blood alcohol levels exceeding 80 mg/dl were observed in the control group upon ethanol-re-access. Lactobacillus-GG or (NAC+ASA) treatments inhibited alcohol intake by 66-80%. The combination of both treatments virtually suppressed (inhibition of 90%) the re-access binge-like drinking, showing additive effects. Treatment with NAC+ASA increased the levels of glutamate transporters xCT and GLT-1 in nucleus accumbens, while Lactobacillus-GG administration increased those of the dopamine transporter (DAT).
CONCLUSIONS: The administration of a well-accepted probiotic may be of value as an adjunct in the treatment of alcohol-use-disorders.}, }
@article {pmid35488243, year = {2022}, author = {Lu, Y and Yuan, X and Wang, M and He, Z and Li, H and Wang, J and Li, Q}, title = {Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies.}, journal = {Journal of hematology & oncology}, volume = {15}, number = {1}, pages = {47}, pmid = {35488243}, issn = {1756-8722}, support = {Grant NO. 81973715//the General program of National Natural Science Foundation of China/ ; Grant NO. ZYYCXTD-C-202001//the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine/ ; Grant NO. 81301912//National Natural Science Foundation of China/ ; Grant NO. BHTPP202008//the Beijing Municipal Health and Scientific and Technological Achievements and Appropriate Technology Promotion Project/ ; Grant NO. yyzscq202003//the "High-value Patent Cultivation" project of the Beijing Friendship Hospital Affiliated to the Capital Medical University/ ; Grant NO. yyqdkt2019-40//the Research Foundation of Beijing Friendship Hospital/ ; }, abstract = {The gut microbiota have long been recognized to play a key role in human health and disease. Currently, several lines of evidence from preclinical to clinical research have gradually established that the gut microbiota can modulate antitumor immunity and affect the efficacy of cancer immunotherapies, especially immune checkpoint inhibitors (ICIs). Deciphering the underlying mechanisms reveals that the gut microbiota reprogram the immunity of the tumor microenvironment (TME) by engaging innate and/or adaptive immune cells. Notably, one of the primary modes by which the gut microbiota modulate antitumor immunity is by means of metabolites, which are small molecules that could spread from their initial location of the gut and impact local and systemic antitumor immune response to promote ICI efficiency. Mechanistic exploration provides novel insights for developing rational microbiota-based therapeutic strategies by manipulating gut microbiota, such as fecal microbiota transplantation (FMT), probiotics, engineered microbiomes, and specific microbial metabolites, to augment the efficacy of ICI and advance the age utilization of microbiota precision medicine.}, }
@article {pmid35487886, year = {2022}, author = {Wang, B and Zhang, L and Wang, Y and Dai, T and Qin, Z and Zhou, F and Zhang, L}, title = {Alterations in microbiota of patients with COVID-19: potential mechanisms and therapeutic interventions.}, journal = {Signal transduction and targeted therapy}, volume = {7}, number = {1}, pages = {143}, pmid = {35487886}, issn = {2059-3635}, support = {31871405 and 31571460//National Natural Science Foundation of China (National Science Foundation of China)/ ; 31925013, 31671457 and 91753139//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The global coronavirus disease 2019 (COVID-19) pandemic is currently ongoing. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high proportion of COVID-19 patients exhibit gastrointestinal manifestations such as diarrhea, nausea, or vomiting. Moreover, the respiratory and gastrointestinal tracts are the primary habitats of human microbiota and targets for SARS-CoV-2 infection as they express angiotensin-converting enzyme-2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) at high levels. There is accumulating evidence that the microbiota are significantly altered in patients with COVID-19 and post-acute COVID-19 syndrome (PACS). Microbiota are powerful immunomodulatory factors in various human diseases, such as diabetes, obesity, cancers, ulcerative colitis, Crohn's disease, and certain viral infections. In the present review, we explore the associations between host microbiota and COVID-19 in terms of their clinical relevance. Microbiota-derived metabolites or components are the main mediators of microbiota-host interactions that influence host immunity. Hence, we discuss the potential mechanisms by which microbiota-derived metabolites or components modulate the host immune responses to SARS-CoV-2 infection. Finally, we review and discuss a variety of possible microbiota-based prophylaxes and therapies for COVID-19 and PACS, including fecal microbiota transplantation (FMT), probiotics, prebiotics, microbiota-derived metabolites, and engineered symbiotic bacteria. This treatment strategy could modulate host microbiota and mitigate virus-induced inflammation.}, }
@article {pmid35486073, year = {2022}, author = {El-Salhy, M and Mazzawi, T and Hausken, T and Hatlebakk, JG}, title = {The fecal microbiota transplantation response differs between patients with severe and moderate irritable bowel symptoms.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/00365521.2022.2064725}, pmid = {35486073}, issn = {1502-7708}, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is a promising intervention for patients with irritable bowel syndrome (IBS). The present study aimed to identify any differences in FMT response between patients with severe and moderate IBS symptoms.
MATERIALS AND METHOD: The study included the 164 patients who participated in our previous study, of which 96 (58.5%) and 68 (41.5%) had severe (S-IBS-S) and moderate (Mo-IBS-S) IBS, respectively. The patients were randomly divided into a placebo group (own feces) and 30-g and 60-g (donor feces) FMT groups. Patients completed three questionnaires that assessed their symptoms and quality of life at baseline and at 2 weeks, 1 month, and 3 months after FMT, and provided fecal samples before and 1 month after FMT. The fecal bacteria were analyzed using the 16S rRNA gene in PCR DNA amplification covering the V3-V9 variable genes.
RESULTS: Response rates of the placebo group did not differ between S-IBS-S and Mo-IBS-S patients at 2 weeks, 1 month and 3 months after FMT. The response rates in the active treatment group were higher in S-IBS-S patients than in Mo-IBS-S patients at each observation time. FMT reduced abdominal symptoms and fatigue and improved the quality of life in patients with both severe and moderate IBS. Patients with S-IBS-S had higher levels of Eubacterium siraeum, and lower levels of Eubacterium rectale than Mo-IBS-S, after FMT.
CONCLUSION: Patients with S-IBS-S have a higher response rate to FMT and a marked improvement in fatigue and in quality of life compared with those with Mo-IBS-S. The clinical trial registration number is NCT03822299 and is available at www.clinicaltrials.gov.}, }
@article {pmid35481834, year = {2022}, author = {Zou, YT and Zhou, J and Zhu, JH and Wu, CY and Shen, H and Zhang, W and Zhou, SS and Xu, JD and Mao, Q and Zhang, YQ and Long, F and Li, SL}, title = {Gut Microbiota Mediates the Protective Effects of Traditional Chinese Medicine Formula Qiong-Yu-Gao against Cisplatin-Induced Acute Kidney Injury.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0075922}, doi = {10.1128/spectrum.00759-22}, pmid = {35481834}, issn = {2165-0497}, abstract = {Our previous study found that Qiong-Yu-Gao (QYG), a traditional Chinese medicine formula derived from Rehmanniae Radix, Poria, and Ginseng Radix, has protective effects against cisplatin-induced acute kidney injury (AKI), but the underlying mechanisms remain unknown. In the present study, the potential role of gut microbiota in the nephroprotective effects of QYG was investigated. We found that QYG treatment significantly attenuated cisplatin-induced AKI and gut dysbiosis, altered the levels of bacterial metabolites, with short-chain fatty acids (SCFAs) such as acetic acid and butyric acid increasing and uremic toxins such as indoxyl sulfate and p-cresyl sulfate reducing, and suppressed histone deacetylase expression and activity. Spearman's correlation analysis found that QYG-enriched fecal bacterial genera Akkermansia, Faecalibaculum, Bifidobacterium, and Lachnospiraceae_NK4A136_group were correlated with the altered metabolites, and these metabolites were also correlated with the biomarkers of AKI, as well as the indicators of fibrosis and inflammation. The essential role of gut microbiota was further verified by both the diminished protective effects with antibiotics-induced gut microbiota depletion and the transferable renal protection with fecal microbiota transplantation. All these results suggested that gut microbiota mediates the nephroprotective effects of QYG against cisplatin-induced AKI, potentially via increasing the production of SCFAs, thus suppressing histone deacetylase expression and activity, and reducing the accumulation of uremic toxins, thereby alleviating fibrosis, inflammation, and apoptosis in renal tissue. IMPORTANCE Cisplatin-induced acute kidney injury is the main limiting factor restricting cisplatin's clinical application. Accumulating evidence indicated the important role of gut microbiota in pathogenesis of acute kidney injury. In the present study, we have demonstrated that gut microbiota mediates the protective effects of traditional Chinese medicine formula Qiong-Yu-Gao against cisplatin-induced acute kidney injury. The outputs of this study would provide scientific basis for future clinical applications of QYG as prebiotics to treat cisplatin-induced acute kidney injury, and gut microbiota may be a promising therapeutic target for chemotherapy-induced nephrotoxicity.}, }
@article {pmid35481347, year = {2022}, author = {Hu, B and Das, P and Lv, X and Shi, M and Aa, J and Wang, K and Duan, L and Gilbert, JA and Nie, Y and Wu, XL}, title = {Effects of 'Healthy' Fecal Microbiota Transplantation against the Deterioration of Depression in Fawn-Hooded Rats.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0021822}, doi = {10.1128/msystems.00218-22}, pmid = {35481347}, issn = {2379-5077}, abstract = {Depression is a recurrent, heterogeneous mood disorder occurring in more than 260 million people worldwide. Gut microbiome dysbiosis is associated with the development of depressive-like behaviors by modulating neuro-biochemical metabolism through the microbiome-gut-brain (MGB) axis. Fecal microbiota transplantation (FMT) has been proposed as a potential therapeutic solution for depression, but the therapeutic efficiency and mechanism are unknown. Here, we performed an FMT from Sprague-Dawley (SD) rats ('healthy' controls) to Fawn-hooded (FH) rats (depression model). Pre-FMT, the FH rats exhibited significantly elevated depressive-like behaviors and distinct neurotransmitter and cytokine levels compared with SD rats. Post-FMT, FH recipients receiving FH fecal microbiota (FH-FH rats) showed aggravated depressive-like behaviors, while the ones receiving SD microbiota (FH-SD rats) had significantly alleviated depressive symptoms, a significant increase in hippocampal neurotransmitters, and a significant decrease of some hippocampal cytokines than FH-FH rats. SD-FMT resulted in the FH-SD rats' gut microbiome resembling the SD donors, and a significant shift in the serum metabolome but not the hippocampal metabolome. Co-occurrence analysis suggests that SD-FMT prevented recipients' depression development via the significant decrease of gut microbial species such as Dialister sp., which led to the recipients' metabolic modulation in serum and hippocampus through the enteric nervous system, the intestinal barrier, and the blood-brain barrier. Our results provided new data pointing to multiple mechanisms of interaction for the impact of gut microbiome modulation on depression therapy. IMPORTANCE Depression is a chronic, recurrent mental disease, which could make the patients commit suicide in severe cases. Considering that gut microbiome dysbiosis could cause depressive symptoms in animals through the MGB axis, the modification of gut microbiota is expected to be a potential therapy for depression, but the daily administration of probiotics is invalid or transient. In this study, we demonstrated that the gut microbiome transferred from a healthy rat model to a depressive rat model could regulate the recipient's neurobiology and behavior via the systematic alternation of the depressive gut microbiota followed by the serum and hippocampal metabolism. These results underline the significance of understanding the impact of gut microbiota on mental disorders and suggest that 'healthy' microbiota transplantation with the function to solve the host's cerebral inflammation may serve as a novel therapeutic strategy for depression.}, }
@article {pmid35479587, year = {2022}, author = {Rapoport, EA and Baig, M and Puli, SR}, title = {Adverse events in fecal microbiota transplantation: a systematic review and meta-analysis.}, journal = {Annals of gastroenterology}, volume = {35}, number = {2}, pages = {150-163}, doi = {10.20524/aog.2022.0695}, pmid = {35479587}, issn = {1108-7471}, abstract = {Background: Fecal microbiota transplantation (FMT) is a highly efficacious procedure used most commonly for the treatment of recurrent Clostridioides difficile infection (CDI). Despite the high value of incorporating FMT into practice, there remain concerns about its safety. To the best of our knowledge, there has not been an updated meta-analysis reporting pooled rates of adverse events in FMT for CDI.
Methods: A search for studies of FMT in patients with CDI was performed with the rate of serious adverse events (SAEs) related to FMT evaluated as the primary outcome. Secondary outcomes included SAEs unrelated to FMT and minor adverse events associated with FMT. A pooled analysis was then performed.
Results: Initial search identified 378 reference articles. Data were extracted from the 61 of these studies that met the inclusion criteria, comprising 5099 patients. Pooled analysis showed that SAEs related to FMT developed in less than 1% of patients. The pooled rate of SAEs not related to FMT was higher at 2.9%. The pooled rate of minor adverse events also showed infrequent self-limited gastrointestinal and systemic discomfort.
Conclusions: This meta-analysis supports FMT as a safe option for treating recurrent CDI. Future randomized trials are needed to improve our current understanding of FMT safety and further examine the improvements in the quality of life of patients treated with FMT compared to standard therapy of antibiotics.}, }
@article {pmid35271353, year = {2022}, author = {Fobofou, SA and Savidge, T}, title = {Microbial metabolites: cause or consequence in gastrointestinal disease?.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {322}, number = {6}, pages = {G535-G552}, doi = {10.1152/ajpgi.00008.2022}, pmid = {35271353}, issn = {1522-1547}, support = {P30-DK56338//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; R01DK130517//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; U01-AI24290//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID)/ ; P01-AI152999//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID)/ ; R01-NR013497//HHS | NIH | National Institute of Nursing Research (NINR)/ ; }, mesh = {*COVID-19 ; Dysbiosis/microbiology ; *Gastrointestinal Diseases ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Systems biology studies have established that changes in gastrointestinal microbiome composition and function can adversely impact host physiology. Notable diseases synonymously associated with dysbiosis include inflammatory bowel diseases, cancer, metabolic disorders, and opportunistic and recurrent pathogen infections. However, there is a scarcity of mechanistic data that advances our understanding of taxonomic correlations with pathophysiological host-microbiome interactions. Generally, to survive a hostile gut environment, microbes are highly metabolically active and produce trans-kingdom signaling molecules to interact with competing microorganisms and the host. These specialized metabolites likely play important homeostatic roles, and identifying disease-specific taxa and their effector pathways can provide better strategies for diagnosis, treatment, and prevention, as well as the discovery of innovative therapeutics. The signaling role of microbial biotransformation products such as bile acids, short-chain fatty acids, polysaccharides, and dietary tryptophan is increasingly recognized, but little is known about the identity and function of metabolites that are synthesized by microbial biosynthetic gene clusters, including ribosomally synthesized and posttranslationally modified peptides (RiPPs), nonribosomal peptides (NRPs), polyketides (PKs), PK-NRP hybrids, and terpenes. Here we consider how bioactive natural products directly encoded by the human microbiome can contribute to the pathophysiology of gastrointestinal disease, cancer, autoimmune, antimicrobial-resistant bacterial and viral infections (including COVID-19). We also present strategies used to discover these compounds and the biological activities they exhibit, with consideration of therapeutic interventions that could emerge from understanding molecular causation in gut microbiome research.}, }
@article {pmid35475976, year = {2022}, author = {Li, S and Zhao, X and Lin, F and Ni, X and Liu, X and Kong, C and Yao, X and Mo, Y and Dai, Q and Wang, J}, title = {Gut Flora Mediates the Rapid Tolerance of Electroacupuncture on Ischemic Stroke by Activating Melatonin Receptor through Regulating Indole-3-Propionic Acid.}, journal = {The American journal of Chinese medicine}, volume = {}, number = {}, pages = {1-28}, doi = {10.1142/S0192415X22500409}, pmid = {35475976}, issn = {1793-6853}, abstract = {Electroacupuncture (EA) is commonly used to treat cerebrovascular diseases. This study aimed to clarify the mechanisms of action of treatments of cerebral ischemic stroke from the perspective of gut microecology. We used a mouse model and cell cultures to investigate the effects of EA on the intestinal microflora in mice models of middle cerebral artery occlusion (MCAO) and the mechanisms underlying the antioxidant activities of metabolites. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota. Metabolomic analysis was performed to characterize the metabolic profile differences between the mice in the EA + MCAO and MCAO groups. Gavaging with feces relieved brain damage in mice that received EA (EA mice) more than in mice that did not (non-EA [NEA] mice). The gut microbial composition and metabolic profiles of the EA and NEA mice were different. In particular, the microbiota from the mice in the EA or EA-FMT groups generated more indole-3-propionic acid (IPA) than the microbiota from the mice in the MCAO or NEA-FMT groups. We confirmed that IPA binds to specific melatonin receptors (MTRs) in target cells and exerts antioxidant effects by adding MTR inhibitors or knocking out the MTR1 gene in vivo and in the oxygen and glucose deprivation/reperfusion models of N2a cell experiments. EA can prevent ischemic stroke by improving the composition of intestinal microbiota in MCAO mice. Moreover, this study reveals a new mechanism of intestinal flora regulation of stroke that differs from inflammation/immunity, namely gut microbiota regulates stroke by affecting IPA levels.}, }
@article {pmid35474500, year = {2022}, author = {Kumar, P and Brazel, D and DeRogatis, J and Valerin, JBG and Whiteson, K and Chow, WA and Tinoco, R and Moyers, JT}, title = {The cure from within? a review of the microbiome and diet in melanoma.}, journal = {Cancer metastasis reviews}, volume = {}, number = {}, pages = {}, pmid = {35474500}, issn = {1573-7233}, abstract = {Therapy for cutaneous melanoma, the deadliest of the skin cancers, is inextricably linked to the immune system. Once thought impossible, cures for metastatic melanoma with immune checkpoint inhibitors have been developed within the last decade and now occur regularly in the clinic. Unfortunately, half of tumors do not respond to checkpoint inhibitors and efforts to further exploit the immune system are needed. Tantalizing associations with immune health and gut microbiome composition suggest we can improve the success rate of immunotherapy. The gut contains over half of the immune cells in our bodies and increasingly, evidence is linking the immune system within our gut to melanoma development and treatment. In this review, we discuss the importance the skin and gut microbiome may play in the development of melanoma. We examine the differences in the microbial populations which inhabit the gut of those who develop melanoma and subsequently respond to immunotherapeutics. We discuss the role of dietary intake on the development and treatment of melanoma. And finally, we review the landscape of published and registered clinical trials therapeutically targeting the microbiome in melanoma through dietary supplements, fecal microbiota transplant, and microbial supplementation.}, }
@article {pmid35472435, year = {2022}, author = {Zhu, L and Ye, C and Hu, B and Xia, H and Bian, Q and Liu, Y and Kong, M and Zhou, S and Liu, H}, title = {Regulation of gut microbiota and intestinal metabolites by Poria cocos oligosaccharides improves glycolipid metabolism disturbance in high-fat diet-fed mice.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109019}, doi = {10.1016/j.jnutbio.2022.109019}, pmid = {35472435}, issn = {1873-4847}, abstract = {In this study, we aimed to explore the effect of Poria cocos oligosaccharides (PCO) on glucolipid metabolism disorder. Based on a high-fat diet (HFD)-induced obese mouse model, we demonstrated that PCO ameliorated glucose intolerance and insulin resistance, decreased the levels of blood glucose (187.8 ± 19.8 mg/dL) and insulin (566.3 ± 53.34 ng/L) in HFD-fed mice compared to the Ctrl group (140.4 ± 7.942 mg/dL for glucose, 423.2 ± 19.56 ng/L for insulin). Moreover, PCO treatment suppressed the mRNA expressions of fatty acid synthesis regulators (decreases of 68.8%, 62.8%, and 32.0% for G6Pase, FASN, and DGAT, respectively, vs HFD group) and pro-inflammatory cytokines in epididymal fat (decreases of 71.9%, 81.5%, 76.0%, 29.3%, and 63.9% for TNF-α, IL-1β, IL-6, COX-5b, and MCP-1, respectively, vs HFD group). Also, PCO treatment alleviated damage to the intestinal barrier of HFD-fed mice. By 16S rDNA gene sequencing, PCO partly restored the imbalance of gut microbiota in HFD-fed mice, accompanied by the reversal of several intestinal metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), and tryptophan metabolites. By Spearman's correlation analysis, we found that the changed gut microbiota and their metabolites were significantly correlated with the alteration of metabolic markers. Finally, the significance of gut microbiota in PCO-mediated improvement on glucolipid metabolism disorder was confirmed by an antibiotic depletion experiment and fecal microbiota transplantation. In summary, PCO may be used as a novel prebiotic in the treatment of glucolipid disorders by reshaping intestinal bacteria structure. Our studies also point towards the potential of Poria cocos as a healthy food in the clinical application to metabolic diseases in the future.}, }
@article {pmid35468731, year = {2022}, author = {Hao, Y and Feng, Y and Yan, X and Chen, L and Zhong, R and Tang, X and Shen, W and Sun, Q and Sun, Z and Ren, Y and Zhang, H and Zhao, Y}, title = {Gut microbiota-testis axis: FMT improves systemic and testicular micro-environment to increase semen quality in type 1 diabetes.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {28}, number = {1}, pages = {45}, pmid = {35468731}, issn = {1528-3658}, support = {31772408//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Clinical data suggest that male reproductive dysfunction especially infertility is a critical issue for type 1 diabetic patient (T1D) because most of them are at the reproductive age. Gut dysbiosis is involved in T1D related male infertility. However, the improved gut microbiota can be used to boost spermatogenesis and male fertility in T1D remains incompletely understood.
METHODS: T1D was established in ICR (CD1) mice with streptozotocin. Alginate oligosaccharide (AOS) improved gut microbiota (fecal microbiota transplantation (FMT) from AOS improved gut microbiota; A10-FMT) was transplanted into the T1D mice by oral administration. Semen quality, gut microbiota, blood metabolism, liver, and spleen tissues were determined to investigate the beneficial effects of A10-FMT on spermatogenesis and underlying mechanisms.
RESULTS: We found that A10-FMT significantly decreased blood glucose and glycogen, and increased semen quality in streptozotocin-induced T1D subjects. A10-FMT improved T1D-disturbed gut microbiota, especially the increase in small intestinal lactobacillus, and blood and testicular metabolome to produce n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to ameliorate spermatogenesis and semen quality. Moreover, A10-FMT can improve spleen and liver functions to strengthen the systemic environment for sperm development. FMT from gut microbiota of control animals (Con-FMT) produced some beneficial effects; however, to a smaller extent.
CONCLUSIONS: AOS-improved gut microbiota (specific microbes) may serve as a novel, promising therapeutic approach for the improvement of semen quality and male fertility in T1D patients via gut microbiota-testis axis.}, }
@article {pmid35467645, year = {2022}, author = {Xiao, Y and Zhong, XS and Liu, X and Li, Q}, title = {Therapeutic Evaluation of Fecal Microbiota Transplantation in an Interleukin 10-deficient Mouse Model.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {182}, pages = {}, doi = {10.3791/63350}, pmid = {35467645}, issn = {1940-087X}, abstract = {With the development of microecology in recent years, the relationship between intestinal bacteria and inflammatory bowel disease (IBD) has attracted considerable attention. Accumulating evidence suggests that dysbiotic microbiota plays an active role in triggering or worsening the inflammatory process in IBD and that fecal microbiota transplantation (FMT) is an attractive therapeutic strategy since transferring a healthy microbiota to IBD patient could restore the appropriate host-microbiota communication. However, the molecular mechanisms are unclear, and the efficacy of FMT has not been very well established. Thus, further studies in animal models of IBD are necessary. In this method, we applied FMT from wild-type C57BL/6J mice to IL-10 deficient mice, a widely used mouse model of colitis. The study elaborates on collecting fecal pellets from the donor mice, making the fecal solution/suspension, administering the fecal solution, and monitoring the disease. We found that FMT significantly mitigated the cardiac impairment in IL-10 knockout mice, underlining its therapeutic potential for IBD management.}, }
@article {pmid35467388, year = {2022}, author = {Jing, Y and Bai, F and Wang, L and Yang, D and Yan, Y and Wang, Q and Zhu, Y and Yu, Y and Chen, Z}, title = {Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0017722}, doi = {10.1128/spectrum.00177-22}, pmid = {35467388}, issn = {2165-0497}, abstract = {The primary traumatic event that causes spinal cord injury (SCI) is followed by a progressive secondary injury featured by vascular disruption and ischemia, inflammatory responses and the release of cytotoxic debris, which collectively add to the hostile microenvironment of the lesioned cord and inhibit tissue regeneration and functional recovery. In a previous study, we reported that fecal microbiota transplantation (FMT) promotes functional recovery in a contusion SCI mouse model; yet whether and how FMT treatment may impact the microenvironment at the injury site are not well known. In the current study, we examined individual niche components and investigated the effects of FMT on microcirculation, inflammation and trophic factor secretion in the spinal cord of SCI mice. FMT treatment significantly improved spinal cord tissue sparing, vascular perfusion and pericyte coverage and blood-spinal cord-barrier (BSCB) integrity, suppressed the activation of microglia and astrocytes, and enhanced the secretion of neurotrophic factors. Suppression of inflammation and upregulation of trophic factors, jointly, may rebalance the niche homeostasis at the injury site and render it favorable for reparative and regenerative processes, eventually leading to functional recovery. Furthermore, microbiota metabolic profiling revealed that amino acids including β-alanine constituted a major part of the differentially detected metabolites between the groups. Supplementation of β-alanine in SCI mice reduced BSCB permeability and increased the number of surviving neurons, suggesting that β-alanine may be one of the mediators of FMT that participates in the modulation and rebalancing of the microenvironment at the injured spinal cord. IMPORTANCE FMT treatment shows a profound impact on the microenvironment that involves microcirculation, blood-spinal cord-barrier, activation of immune cells, and secretion of neurotrophic factors. Analysis of metabolic profiles reveals around 22 differentially detected metabolites between the groups, and β-alanine was further chosen for functional validation experiments. Supplementation of SCI mice with β-alanine significantly improves neuronal survival, and the integrity of blood-spinal cord-barrier at the lesion site, suggesting that β-alanine might be one of the mediators following FMT that has contributed to the recovery.}, }
@article {pmid35465162, year = {2022}, author = {Feng, T and Liu, Y}, title = {Microorganisms in the reproductive system and probiotic's regulatory effects on reproductive health.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {1541-1553}, doi = {10.1016/j.csbj.2022.03.017}, pmid = {35465162}, issn = {2001-0370}, abstract = {The presence of microbial communities in the reproductive tract has been revealed, and this resident microbiota is involved in the maintenance of health. Intentional modulation via probiotics has been proposed as a possible strategy to enhance reproductive health and reduce the risk of diseases. The male seminal microbiota has been suggested as an important factor that influences a couple's health, pregnancy outcomes, and offspring health. Probiotics have been reported to play a role in male fertility and to affect the health of mothers and offspring. While the female reproductive microbiota is more complicated and has been identified in both the upper and lower reproductive systems, they together contribute to health maintenance. Probiotics have shown regulatory effects on the female reproductive tract, thereby contributing to homeostasis of the tract and influencing the health of offspring. Further, through transmission of bacteria or through other indirect mechanisms, the parent's reproductive microbiota and probiotic intervention influence infant gut colonization and immunity development, with potential health consequences. In vitro and in vivo studies have explored the mechanisms underlying the benefits of probiotic administration and intervention, and an array of positive results, such as modulation of microbiota composition, regulation of metabolism, promotion of the epithelial barrier, and improvement of immune function, have been observed. Herein, we review the state of the art in reproductive system microbiota and its role in health and reproduction, as well as the beneficial effects of probiotics on reproductive health and their contributions to the prevention of associated diseases.}, }
@article {pmid35463939, year = {2022}, author = {Hammeken, LH and Baunwall, SMD and Dahlerup, JF and Hvas, CL and Ehlers, LH}, title = {Health-related quality of life in patients with recurrent Clostridioides difficile infections.}, journal = {Therapeutic advances in gastroenterology}, volume = {15}, number = {}, pages = {17562848221078441}, doi = {10.1177/17562848221078441}, pmid = {35463939}, issn = {1756-283X}, abstract = {Background: The health-related quality of life (HrQoL) can be substantially affected in patients with recurrent Clostridioides difficile infection (rCDI) but the impact of effective treatment of the infection remains unclear. This study aimed to evaluate the HrQoL in patients with rCDI and estimate the gain in HrQoL associated with effective treatment of rCDI.
Methods: Patients' HrQoL was estimated based on EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaires obtained from a Danish randomised controlled trial (RCT). In the RCT, 64 patients with rCDI were randomised to receive either vancomycin (n = 16), fidaxomicin (n = 24) or faecal microbiota transplantation (FMT) preceded by vancomycin (n = 24). The primary outcome in the RCT was rCDI resolution. Patients were closely monitored during the RCT, and rescue FMT was offered to those who failed their primary treatment. Patients' HrQoL was measured at baseline and at 8- and 26-weeks follow-up. Linear regression analyses conditional on the differences between baseline and follow-up measurements were used to assess statistical significance (p < 0.05).
Results: Within 26 weeks of follow-up, 13 (81%) patients treated with vancomycin, 12 (50%) patients treated with fidaxomicin, and 3 (13%) patients treated with FMT had a subsequent recurrence and received a rescue FMT. The average HrQoL for untreated patients with rCDI was 0.675. After receiving effective treatment, this value increased by 0.139 to 0.813 (p < 0.001) at week 8 and by 0.098 to 0.773 (p = 0.003) at week 26 of follow-up compared with baseline.
Conclusion: The HrQoL was adversely affected in patients with an active episode of rCDI but increased substantially after receiving an effective treatment algorithm in which rescue FMT was provided in case of a primary treatment failure.
Trial registration: The RCT was preregistered at EudraCT (j.no. 2015-003004-24, https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003004-24/results) and at ClinicalTrials.gov (study identifier NCT02743234, https://clinicaltrials.gov/ct2/show/NCT02743234).}, }
@article {pmid35462505, year = {2022}, author = {Zhou, Y and Li, YY and Liu, Y}, title = {[Effect of fecal microbiota transplantation on type 1 diabetes mellitus in non-obese diabetic mice and its underlying mechanism].}, journal = {Zhonghua yi xue za zhi}, volume = {102}, number = {16}, pages = {1224-1231}, doi = {10.3760/cma.j.cn112137-20210907-02043}, pmid = {35462505}, issn = {0376-2491}, support = {82070849, 81770778, 81800735//National Natural Science Foundation of China/ ; 20182015//Innovation and Entrepreneurship Team Project in Jiangsu Province/ ; }, abstract = {Objective: To investigate the effects of fecal microbiota transplantation (FMT) on non-obese diabetic (NOD) mice of type 1 diabetes mellitus (T1DM) and its underlying mechanisms. Methods: A total of 8-9 week-female NOD mice were randomly divided into control (n=36) and FMT groups (n=36) according to the random number table. Fecal microbiota from C57BL/6 mice were transplanted into FMT group, and control group were transplanted with microbiota from themselves, once every two days for 5 times. The insulitis score and incidence of T1DM were compared between two groups;16S rRNA gene sequencing was used to evaluate the structure of fecal bacteria in NOD mice. The expressions of intestinal barrier related genes were detected by real-time quantitative PCR. The proportions of regulatory T cells (Tregs), helper T cell (Th)-1 and Th17 in the enteric-pancreatic immune axis were detected by flow cytometry. Amino acid in serum was measured by amino acid metabolomics. Results: Incidence of T1DM in NOD mice from FMT group was 40.9% (9/22), lower than 72.7% (13/22) from control group at 26 weeks of age (P=0.034). FMT promoted colonization of probiotics such as Lactobacillus, Clostridium_sp_ND2, Candidatus_Arthromitus and Clostridiaceae_1; mRNA of intestinal barrier related genes were up-regulated in FMT group [ mucins(Muc)-1: 0.93±0.29 vs 2.97±0.79, P=0.036; Muc2: 0.72±0.39 vs 10.70±3.54, P=0.019;Muc3: 1.79±0.69 vs 10.97±2.78, P=0.009;Muc4: 1.01±0.23 vs 2.42±0.49, P=0.029;Occludin(Ocln): 0.96±0.08 vs 1.81±0.36, P=0.045; Claudin(Cldn)-1:0.94±0.17 vs 2.20±0.43, P=0.022] compared to control. The proportions of Treg in mesenteric lymphoid node, pancreatic lymph node and peyer's patches of FMT group [(6.10±0.49)% vs (7.54±0.27)%, P=0.020;(5.28±0.39)% vs (6.42±0.34)%, P=0.048;(6.78±0.42)% vs (7.88±0.13)%, P=0.029] were increased compared to control,while proportions of Th1 [(1.02±0.06)% vs (0.83±0.06)%, P=0.040;(0.82±0.10)% vs (0.56±0.05)%, P=0.038;(1.28±0.12) vs (0.85±0.07), P=0.012] and proportions of Th17 [(0.40±0.01)% vs (0.30±0.02)%, P=0.004;(0.40±0.02)% vs (0.31±0.02)%, P=0.008;(0.51±0.06) vs (0.36±0.02), P=0.027] were decreased. The contents of leucine [(92.86±7.32) vs (91.87±12.62) μmol/L, P=0.027], valine [(162.74±15.97) vs (155.89±25.70) μmol/L, P=0.046] and isoleucine [(75.65±5.59) vs (73.61±9.67) μmol/L, P=0.048] in serum were decreased in FMT group. Conclusions: FMT can alleviate insulitis and T1DM occurrence in NOD mice, of which mechanism may be related to remodeling gut microbiota and improving intestinal barrier function, affecting immune response of enteric-pancreatic immune axis, correcting amino acid metabolism disorder and reducing the accumulation of branch chain amino acids in NOD mice.}, }
@article {pmid35461908, year = {2022}, author = {Macareño-Castro, J and Solano-Salazar, A and Dong, LT and Mohiuddin, M and Espinoza, JL}, title = {Fecal microbiota transplantation for Carbapenem-Resistant Enterobacteriaceae: A systematic review.}, journal = {The Journal of infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jinf.2022.04.028}, pmid = {35461908}, issn = {1532-2742}, abstract = {The prevalence of Carbapenem-resistant Enterobacteriaceae (CRE) has increased dramatically in recent years and has become a global public health issue. Since carbapenems are considered the last drugs of choice, infections caused by these pathogens are difficult to treat and carry a high risk of mortality. Several antibiotic combination regimens have been utilized for the management of CRE infections or to eradicate colonization in CRE carriers with variable clinical responses. In addition, recent studies have explored the use of fecal microbiota transplantation (FMT) to eradicate CRE infections. Here, we conducted a systematic review of publications in which FMT was used to eliminate CRE colonization in infected individuals. We searched the PubMed, Cochrane, and Medline databases up to November 30, 2021. Ten studies (209 patients) met the inclusion criteria for this review with three articles describing retrospective cohorts (n = 53 patients) and seven reporting prospective data (n = 156 patients), including one randomized open-label clinical trial. All studies were published between 2017 and 2021 with eight studies from Europe and two from South Korea. There were substantial variations in terms of outcome measurements and study endpoint among these studies. Among the 112 FMT recipients with confirmed CRE colonization, CRE decolonization was reported in 55/90 cases at one month after FMT and at the end of the study follow-up (6-12 months), decolonization was documented in 74/94 (78.7%) patients. The predominant CRE strains reported were Klebsiella pneumoniae and Escherichia coli and the most frequently documented carbapenemases were KPC, OXA-48, and NDM. In general, FMT was well tolerated, with no severe complications reported even in immunosuppressed patients and in those with multiple underlying conditions. In conclusion, FMT appears to be safe and effective in eradicating CRE colonization, however, more studies, especially randomized trials, are needed to validate the safety and clinical utility of FMT for CRE eradication.}, }
@article {pmid35461318, year = {2022}, author = {Hou, K and Wu, ZX and Chen, XY and Wang, JQ and Zhang, D and Xiao, C and Zhu, D and Koya, JB and Wei, L and Li, J and Chen, ZS}, title = {Microbiota in health and diseases.}, journal = {Signal transduction and targeted therapy}, volume = {7}, number = {1}, pages = {135}, pmid = {35461318}, issn = {2059-3635}, abstract = {The role of microbiota in health and diseases is being highlighted by numerous studies since its discovery. Depending on the localized regions, microbiota can be classified into gut, oral, respiratory, and skin microbiota. The microbial communities are in symbiosis with the host, contributing to homeostasis and regulating immune function. However, microbiota dysbiosis can lead to dysregulation of bodily functions and diseases including cardiovascular diseases (CVDs), cancers, respiratory diseases, etc. In this review, we discuss the current knowledge of how microbiota links to host health or pathogenesis. We first summarize the research of microbiota in healthy conditions, including the gut-brain axis, colonization resistance and immune modulation. Then, we highlight the pathogenesis of microbiota dysbiosis in disease development and progression, primarily associated with dysregulation of community composition, modulation of host immune response, and induction of chronic inflammation. Finally, we introduce the clinical approaches that utilize microbiota for disease treatment, such as microbiota modulation and fecal microbial transplantation.}, }
@article {pmid35458209, year = {2022}, author = {Thye, AY and Law, JW and Tan, LT and Thurairajasingam, S and Chan, KG and Letchumanan, V and Lee, LH}, title = {Exploring the Gut Microbiome in Myasthenia Gravis.}, journal = {Nutrients}, volume = {14}, number = {8}, pages = {}, doi = {10.3390/nu14081647}, pmid = {35458209}, issn = {2072-6643}, support = {FRGS/1/2019/SKK08/MUSM/02/7//Fundamental Research Grant Scheme/ ; STG-000051//Jeffrey Cheah School of Medicine and Health Sciences Strategic Grant 2021/ ; }, abstract = {The human gut microbiota is vital for maintaining human health in terms of immune system homeostasis. Perturbations in the composition and function of microbiota have been associated with several autoimmune disorders, including myasthenia gravis (MG), a neuromuscular condition associated with varying weakness and rapid fatigue of the skeletal muscles triggered by the host's antibodies against the acetylcholine receptor (AChR) in the postsynaptic muscle membrane at the neuromuscular junction (NMJ). It is hypothesized that perturbation of the gut microbiota is associated with the pathogenesis of MG. The gut microbiota community profiles are usually generated using 16S rRNA gene sequencing. Compared to healthy individuals, MG participants had an altered gut microbiota's relative abundance of bacterial taxa, particularly with a drop in Clostridium. The microbial diversity related to MG severity and the overall fecal short-chain fatty acids (SCFAs) were lower in MG subjects. Changes were also found in terms of serum biomarkers and fecal metabolites. A link was found between the bacterial Operational Taxonomic Unit (OTU), some metabolite biomarkers, and MG's clinical symptoms. There were also variations in microbial and metabolic markers, which, in combination, could be used as an MG diagnostic tool, and interventions via fecal microbiota transplant (FMT) could affect MG development. Probiotics may influence MG by restoring the gut microbiome imbalance, aiding the prevention of MG, and lowering the risk of gut inflammation by normalizing serum biomarkers. Hence, this review will discuss how alterations of gut microbiome composition and function relate to MG and the benefits of gut modulation.}, }
@article {pmid35458198, year = {2022}, author = {Liu, X and Hu, G and Wang, A and Long, G and Yang, Y and Wang, D and Zhong, N and Jia, J}, title = {Black Tea Reduces Diet-Induced Obesity in Mice via Modulation of Gut Microbiota and Gene Expression in Host Tissues.}, journal = {Nutrients}, volume = {14}, number = {8}, pages = {}, doi = {10.3390/nu14081635}, pmid = {35458198}, issn = {2072-6643}, abstract = {Black tea was reported to alter the microbiome populations and metabolites in diet-induced obese mice and displays properties that prevent obesity, but the underlying mechanism of the preventative effect of black tea on high-fat diet (HFD) induced obesity has not been elucidated. Epigenetic studies are a useful tool for determining the relationship between obesity and environment. Here, we show that the water extract of black tea (Lapsang souchong, LS) reverses HFD-induced gut dysbiosis, alters the tissue gene expression, changes the level of a major epigenetic modification (DNA methylation), and prevents obesity in HFD feeding mice. The anti-obesity properties of black tea are due to alkaloids, which are the principal active components. Our data indicate that the anti-obesity benefits of black tea are transmitted via fecal transplantation, and the change of tissue gene expression and the preventative effects on HFD-induced obesity in mice of black tea are dependent on the gut microbiota. We further show that black tea could regulate the DNA methylation of imprinted genes in the spermatozoa of high-fat diet mice. Our results show a mechanistic link between black tea, changes in the gut microbiota, epigenetic processes, and tissue gene expression in the modulation of diet-induced metabolic dysfunction.}, }
@article {pmid35456788, year = {2022}, author = {van Thiel, IAM and Rahman, S and Hakvoort, TBM and Davids, M and Verseijden, C and van Hamersveld, PHP and Bénard, MV and Lodders, MH and Boekhout, T and van den Wijngaard, RM and Heinsbroek, SEM and Ponsioen, CY and de Jonge, WJ}, title = {Fecal Filobasidium Is Associated with Clinical Remission and Endoscopic Response following Fecal Microbiota Transplantation in Mild-to-Moderate Ulcerative Colitis.}, journal = {Microorganisms}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/microorganisms10040737}, pmid = {35456788}, issn = {2076-2607}, support = {LSHM17028//Health Holland/ ; LSHM20085//Health Holland/ ; }, abstract = {Fecal microbiota transplantation (FMT) has the potential to restore (bacterial and fungal) microbial imbalance in ulcerative colitis (UC) patients and contribute to disease remission. Here, we aimed to identify fecal fungal species associated with the induction of clinical remission and endoscopic response to FMT for patients with mild-to-moderate ulcerative colitis. We analyzed the internal transcribed spacer 1 (ITS1)-based mycobiota composition in fecal samples from patients (n = 31) and donors (n = 7) that participated previously in a double-blinded randomized control trial evaluating the efficacy of two infusions of donor FMT compared with autologous FMT. The abundance of the yeast genus Filobasidium in fecal material used for transplantation was shown to correlate with clinical remission following FMT, irrespective of its presence in the material of donor or autologous fecal microbiota transfer. The amplified sequence variants within the genus Filobasidium most closely resembled Filobasidium magnum. Monocyte-derived macrophages and HT29 epithelial cells were stimulated with fungal species. Especially Filobasidium floriforme elicited an IL10 response in monocyte-derived macrophages, along with secretion of other cytokines following stimulation with other Filobasidium species. No effect of Filobasidium spp. was seen on epithelial wound healing in scratch assays. In conclusion, the enriched presence of Filobasidium spp. in donor feces is associated with the positive response to FMT for patients with UC and hence it may serve as a predictive fungal biomarker for successful FMT.}, }
@article {pmid35456735, year = {2022}, author = {Monteiro, RC and Rafeh, D and Gleeson, PJ}, title = {Is There a Role for Gut Microbiome Dysbiosis in IgA Nephropathy?.}, journal = {Microorganisms}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/microorganisms10040683}, pmid = {35456735}, issn = {2076-2607}, support = {11-IDEX-0005-02//Agence Nationale de la Recherche/ ; EQU201903007816//Fondation pour la Recherche Stratégique/ ; }, abstract = {Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and one of the leading causes of renal failure worldwide. The pathophysiology of IgAN involves nephrotoxic IgA1-immune complexes. These complexes are formed by galactose-deficient (Gd) IgA1 with autoantibodies against the hinge region of Gd-IgA1 as well as soluble CD89, an immune complex amplifier with an affinity for mesangial cells. These multiple molecular interactions result in the induction of the mesangial IgA receptor, CD71, injuring the kidney and causing disease. This review features recent immunological and microbiome studies that bring new microbiota-dependent mechanisms developing the disease based on data from IgAN patients and a humanized mouse model of IgAN. Dysbiosis of the microbiota in IgAN patients is also discussed in detail. Highlights of this review underscore that nephrotoxic IgA1 in the humanized mice originates from mucosal surfaces. Fecal microbiota transplantation (FMT) experiments in mice using stools from patients reveal a possible microbiota dysbiosis in IgAN with the capacity to induce progression of the disease whereas FMT from healthy hosts has beneficial effects in mice. The continual growth of knowledge in IgAN patients and models can lead to the development of new therapeutic strategies targeting the microbiota to treat this disease.}, }
@article {pmid35456041, year = {2022}, author = {Sonali, S and Ray, B and Ahmed Tousif, H and Rathipriya, AG and Sunanda, T and Mahalakshmi, AM and Rungratanawanich, W and Essa, MM and Qoronfleh, MW and Chidambaram, SB and Song, BJ}, title = {Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review.}, journal = {Cells}, volume = {11}, number = {8}, pages = {}, doi = {10.3390/cells11081362}, pmid = {35456041}, issn = {2073-4409}, abstract = {Depression is a highly common mental disorder, which is often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated a clear correlation between gut dysbiosis (GD) or gut microbial dysbiosis and the development of anxiety or depressive behaviors. The gut microbiome communicates with the brain through the neural, immune, and metabolic pathways, either directly (via vagal nerves) or indirectly (via gut- and microbial-derived metabolites as well as gut hormones and endocrine peptides, including peptide YY, pancreatic polypeptide, neuropeptide Y, cholecystokinin, corticotropin-releasing factor, glucagon-like peptide, oxytocin, and ghrelin). Maintaining healthy gut microbiota (GM) is now being recognized as important for brain health through the use of probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), etc. A few approaches exert antidepressant effects via restoring GM and hypothalamus-pituitary-adrenal (HPA) axis functions. In this review, we have summarized the etiopathogenic link between gut dysbiosis and depression with preclinical and clinical evidence. In addition, we have collated information on the recent therapies and supplements, such as probiotics, prebiotics, short-chain fatty acids, and vitamin B12, omega-3 fatty acids, etc., which target the gut-brain axis (GBA) for the effective management of depressive behavior and anxiety.}, }
@article {pmid35455639, year = {2022}, author = {Di Domenico, M and Ballini, A and Boccellino, M and Scacco, S and Lovero, R and Charitos, IA and Santacroce, L}, title = {The Intestinal Microbiota May Be a Potential Theranostic Tool for Personalized Medicine.}, journal = {Journal of personalized medicine}, volume = {12}, number = {4}, pages = {}, doi = {10.3390/jpm12040523}, pmid = {35455639}, issn = {2075-4426}, abstract = {The human intestine is colonized by a huge number of microorganisms from the moment of birth. This set of microorganisms found throughout the human body, is called the microbiota; the microbiome indicates the totality of genes that the microbiota can express, i.e., its genetic heritage. Thus, microbiota participates in and influences the proper functioning of the organism. The microbiota is unique for each person; it differs in the types of microorganisms it contains, the number of each microorganism, and the ratio between them, but mainly it changes over time and under the influence of many factors. Therefore, the correct functioning of the human body depends not only on the expression of its genes but also on the expression of the genes of the microorganisms it coexists with. This fact makes clear the enormous interest of community science in studying the relationship of the human microbiota with human health and the incidence of disease. The microbiota is like a unique personalized "mold" for each person; it differs quantitatively and qualitatively for the microorganisms it contains together with the relationship between them, and it changes over time and under the influence of many factors. We are attempting to modulate the microbial components in the human intestinal microbiota over time to provide positive feedback on the health of the host, from intestinal diseases to cancer. These interventions to modulate the intestinal microbiota as well as to identify the relative microbiome (genetic analysis) can range from dietary (with adjuvant prebiotics or probiotics) to fecal transplantation. This article researches the recent advances in these strategies by exploring their advantages and limitations. Furthermore, we aim to understand the relationship between intestinal dysbiosis and pathologies, through the research of resident microbiota, that would allow the personalization of the therapeutic antibiotic strategy.}, }
@article {pmid35453611, year = {2022}, author = {Lian, WS and Wang, FS and Chen, YS and Tsai, MH and Chao, HR and Jahr, H and Wu, RW and Ko, JY}, title = {Gut Microbiota Ecosystem Governance of Host Inflammation, Mitochondrial Respiration and Skeletal Homeostasis.}, journal = {Biomedicines}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/biomedicines10040860}, pmid = {35453611}, issn = {2227-9059}, support = {NHRI-EX110-11029SI//National Health Research Institutes/ ; CORPG8L0361, and CMRPG8K0041-43//Chang Gung Memorial Hospital/ ; }, abstract = {Osteoporosis and osteoarthritis account for the leading causes of musculoskeletal dysfunction in older adults. Senescent chondrocyte overburden, inflammation, oxidative stress, subcellular organelle dysfunction, and genomic instability are prominent features of these age-mediated skeletal diseases. Age-related intestinal disorders and gut dysbiosis contribute to host tissue inflammation and oxidative stress by affecting host immune responses and cell metabolism. Dysregulation of gut microflora correlates with development of osteoarthritis and osteoporosis in humans and rodents. Intestinal microorganisms produce metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide, and liposaccharides, affecting mitochondrial function, metabolism, biogenesis, autophagy, and redox reactions in chondrocytes and bone cells to regulate joint and bone tissue homeostasis. Modulating the abundance of Lactobacillus and Bifidobacterium, or the ratio of Firmicutes and Bacteroidetes, in the gut microenvironment by probiotics or fecal microbiota transplantation is advantageous to suppress age-induced chronic inflammation and oxidative damage in musculoskeletal tissue. Supplementation with gut microbiota-derived metabolites potentially slows down development of osteoarthritis and osteoporosis. This review provides latest molecular and cellular insights into the biological significance of gut microorganisms and primary and secondary metabolites important to cartilage and bone integrity. It further highlights treatment options with probiotics or metabolites for modulating the progression of these two common skeletal disorders.}, }
@article {pmid35453587, year = {2022}, author = {Biliński, J and Jasiński, M and Basak, GW}, title = {The Role of Fecal Microbiota Transplantation in the Treatment of Acute Graft-versus-Host Disease.}, journal = {Biomedicines}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/biomedicines10040837}, pmid = {35453587}, issn = {2227-9059}, abstract = {The number of allogeneic hematopoietic stem cell transplantations conducted worldwide is constantly rising. Together with that, the absolute number of complications after the procedure is increasing, with graft-versus-host disease (GvHD) being one of the most common. The standard treatment is steroid administration, but only 40-60% of patients will respond to the therapy and some others will be steroid-dependent. There is still no consensus regarding the best second-line option, but fecal microbiota transplantation (FMT) has shown encouraging preliminary and first clinically relevant results in recent years and seems to offer great hope for patients. The reason for treatment of steroid-resistant acute GvHD using this method derives from studies showing the significant immunomodulatory role played by the intestinal microbiota in the pathogenesis of GvHD. Depletion of commensal microbes is accountable for aggravation of the disease and is associated with decreased overall survival. In this review, we present the pathogenesis of GvHD, with special focus on the special role of the gut microbiota and its crosstalk with immune cells. Moreover, we show the results of studies and case reports to date regarding the use of FMT in the treatment of steroid-resistant acute GvHD.}, }
@article {pmid35451337, year = {2022}, author = {Caira-Chuquineyra, B and Fernandez-Guzman, D and Soriano-Moreno, DR and Fernandez-Morales, J and Flores-Lovon, K and Medina-Ramirez, SA and Gonzales-Uribe, AG and Pelayo-Luis, IP and Gonzales-Zamora, JA and Huaringa-Marcelo, J}, title = {Fecal microbiota transplantation for people living with HIV: A scoping review.}, journal = {AIDS research and human retroviruses}, volume = {}, number = {}, pages = {}, doi = {10.1089/AID.2022.0016}, pmid = {35451337}, issn = {1931-8405}, abstract = {The aim of the present scoping review was to determine the characteristics of studies evaluating fecal microbiota transplantation (FMT), as well as its effects and safety as a therapeutic intervention for people living with HIV. We conducted a scoping review following the methodology of the Joanna Briggs Institute. We searched the following databases: PubMed, Web of Science, Scopus, Embase, Cochrane Library, and Medline until September 19, 2021. Studies that used FMT in people living with HIV and explored its effects on the health of these people were included. Two randomized and two uncontrolled clinical trials with a total of 55 participants were included. Participants were well-controlled HIV infected people. Regarding microbiota changes, three studies found significant post-FMT increases in Fusobacterium, Prevotella, α-diversity, Chao-index, and/or Shannon-index, and/or decreases in Bacteroides. Regarding markers of intestinal damage, one study found a decrease in intestinal fatty-acid binding protein post- FMT, and another study found an increase in zonulin. Other outcomes evaluated by the studies were: markers of immune and inflammatory activation, markers of immunocompetence (CD4+, and CD8+ T lymphocytes), and HIV viral load; however, none showed significant changes. Clinical outcomes were not evaluated by these studies. Regarding the safety of FMT, only mild adverse events were appreciated. No serious adverse events were reported. The clinical evidence for FMT in people living with HIV is sparse. FMT appears to have good tolerability and, no serious adverse events have been reported so far. Further clinical trials and evaluation of clinically important biomedical outcomes for FMT in people living with HIV are needed.}, }
@article {pmid35449107, year = {2022}, author = {Wang, Y and Li, H}, title = {Gut microbiota modulation: a tool for the management of colorectal cancer.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {178}, pmid = {35449107}, issn = {1479-5876}, abstract = {Colorectal cancer (CRC) is the second cause of cancer death and the third most frequently diagnosed cancer. Besides the lifestyle, genetic and epigenetic alterations, and environmental factors, gut microbiota also plays a vital role in CRC development. The interruption of the commensal relationship between gut microbiota and the host could lead to an imbalance in the bacteria population, in which the pathogenic bacteria become the predominant population in the gut. Different therapeutic strategies have been developed to modify the gut immune system, prevent pathogen colonization, and alter the activity and composition of gut microbiota, such as prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT). Even though the employed strategies exhibit promising results, their translation into the clinic requires evaluating potential implications and risks, as well as assessment of their long-term effects. This study was set to review the gut microbiota imbalances and their relationship with CRC and their effects on CRC therapy, including chemotherapy and immunotherapy. More importantly, we reviewed the strategies that have been used to modulate gut microbiota, their impact on the treatment of CRC, and the challenges of each strategy.}, }
@article {pmid35446385, year = {2022}, author = {}, title = {Eshel A, Sharon I, Nagler A, et al. Origins of bloodstream infections following fecal microbiota transplantation: a strain-level analysis. Blood Adv. 2022;6(2):568-573.}, journal = {Blood advances}, volume = {6}, number = {8}, pages = {2578-2580}, doi = {10.1182/bloodadvances.2022007476}, pmid = {35446385}, issn = {2473-9537}, }
@article {pmid35446112, year = {2022}, author = {Hao, Y and Feng, Y and Yan, X and Chen, L and Ma, X and Tang, X and Zhong, R and Sun, Z and Agarwal, M and Zhang, H and Zhao, Y}, title = {Gut Microbiota-Testis Axis: FMT Mitigates High-Fat Diet-Diminished Male Fertility via Improving Systemic and Testicular Metabolome.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0002822}, doi = {10.1128/spectrum.00028-22}, pmid = {35446112}, issn = {2165-0497}, abstract = {High-fat diet (HFD)-induced obesity is known to be associated with reduced male fertility and decreased semen quality in humans. HFD-related male infertility is a growing issue worldwide, and it is crucial to overcome this problem to ameliorate the distress of infertile couples. For the first time, we discovered that fecal microbiota transplantation (FMT) of alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) ameliorated HFD-decreased semen quality (sperm concentration: 286.1 ± 14.1 versus 217.9 ± 17.4 million/mL; sperm motility: 40.1 ± 0.7% versus 29.0 ± 0.9%), and male fertility (pregnancy rate: 87.4 ± 1.1% versus 70.2 ± 6.1%) by benefiting blood and testicular metabolome. A10-FMT improved HFD-disturbed gut microbiota by increasing gut Bacteroides (colon: 24.9 ± 1.1% versus 8.3 ± 0.6%; cecum: 10.2 ± 0.7% versus 3.6 ± 0.7%) and decreasing Mucispirillum (colon: 0.3 ± 0.1% versus 2.8 ± 0.4%; cecum: 2.3 ± 0.5% versus 6.6 ± 0.7%). A10-FMT benefited gut microbiota to improve liver function by adjusting lipid metabolism to produce n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (blood: 55.5 ± 18.7 versus 20.3 ± 2.4) and docosahexaenoic acid (testis: 121.2 ± 6.2 versus 89.4 ± 6.7), thus ameliorating HFD-impaired testicular microenvironment to rescue spermatogenesis and increase semen quality and fertility. The findings indicated that AOS-improved gut microbiota may be a promising strategy to treat obesity or metabolic issues-related male infertility in the future. IMPORTANCE HFD decreases male fertility via upsetting gut microbiota and transplantation of AOS-benefited gut microbiota (A10-FMT) improves gut microbiota to ameliorate HFD-reduced male fertility. Moreover, A10-FMT improved liver function to benefit the blood metabolome and simultaneously ameliorated the testicular microenvironment to turn the spermatogenesis process on. We demonstrated that AOS-benefited gut microbiota could be applied to treat infertile males with obesity and metabolic issues induced by HFD.}, }
@article {pmid35444617, year = {2022}, author = {Zhang, WH and Jin, ZY and Yang, ZH and Zhang, JY and Ma, XH and Guan, J and Sun, BL and Chen, X}, title = {Fecal Microbiota Transplantation Ameliorates Active Ulcerative Colitis by Downregulating Pro-inflammatory Cytokines in Mucosa and Serum.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {818111}, doi = {10.3389/fmicb.2022.818111}, pmid = {35444617}, issn = {1664-302X}, abstract = {Background: Ulcerative colitis (UC) is a multi-factor disease characterized by alternating remission periods and repeated occurrence. It has been shown that fecal microbiota transplantation (FMT) is an emerging and effective approach for UC treatment. Since most existing studies chose adults as donors for fecal microbiota, we conducted this study to determine the long-term efficacy and safety of the microbiota from young UC patient donors and illustrate its specific physiological effects.
Methods: Thirty active UC patients were enrolled and FMT were administered with the first colonoscopy and two subsequent enema/transendoscopic enteral tubing (TET) practical regimens in The First Affiliated Hospital of Anhui Medical University in China. Disease activity and inflammatory biomarkers were assessed 6 weeks/over 1 year after treatment. The occurrence of adverse events was also recorded. The samples from blood and mucosa were collected to detect the changes of inflammatory biomarkers and cytokines. The composition of gut and oral microbiota were also sampled and sequenced to confirm the alteration of microbial composition.
Results: Twenty-seven patients completed the treatment, among which 16 (59.3%) achieved efficacious clinical response and 11 (40.7%) clinical remission. Full Mayo score and calprotectin dropped significantly and remained stable over 1 year. FMT also significantly reduced the levels of C-reactive protein (CRP), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). The gut microbiota altered significantly with increased bacterial diversity and decreased metabolic diversity in responsive patients. The pro-inflammatory enterobacteria decreased after FMT and the abundance of Collinsella increased. Accordingly, the altered metabolic functions, including antigen synthesis, amino acids metabolism, short chain fatty acid production, and vitamin K synthesis of microbiota, were also corrected by FMT.
Conclusion: Fecal microbiota transplantation seems to be safe and effective for active UC patients who are nonresponsive to mesalazine or prednisone in the long-term. FMT could efficiently downregulate pro-inflammatory cytokines to ameliorate the inflammation.}, }
@article {pmid35278396, year = {2022}, author = {Haifer, C and Paramsothy, S and Kaakoush, NO and Leong, RW}, title = {Oral faecal microbiota transplantation in ulcerative colitis - Authors' reply.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {7}, number = {4}, pages = {286-287}, doi = {10.1016/S2468-1253(22)00045-0}, pmid = {35278396}, issn = {2468-1253}, mesh = {*Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid35278395, year = {2022}, author = {Yuan, TY and Rajesh, R and Tan, M}, title = {Oral faecal microbiota transplantation in ulcerative colitis.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {7}, number = {4}, pages = {286}, doi = {10.1016/S2468-1253(21)00469-6}, pmid = {35278395}, issn = {2468-1253}, mesh = {*Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid34393197, year = {2022}, author = {Lucarini, E and Di Pilato, V and Parisio, C and Micheli, L and Toti, A and Pacini, A and Bartolucci, G and Baldi, S and Niccolai, E and Amedei, A and Rossolini, GM and Nicoletti, C and Cryan, JF and O'Mahony, SM and Ghelardini, C and Di Cesare Mannelli, L}, title = {Visceral sensitivity modulation by faecal microbiota transplantation: the active role of gut bacteria in pain persistence.}, journal = {Pain}, volume = {163}, number = {5}, pages = {861-877}, doi = {10.1097/j.pain.0000000000002438}, pmid = {34393197}, issn = {1872-6623}, mesh = {Animals ; Bacteria ; Colon/pathology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Mice ; Rats ; *Visceral Pain/drug therapy ; }, abstract = {ABSTRACT: Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing postinflammatory visceral pain persistence. Colitis was induced in mice by intrarectally injecting 2,4-dinitrobenzenesulfonic acid (DNBS). The effect of faecal microbiota transplantation from viscerally hypersensitive DNBS-treated and naive donors was evaluated in control rats after an antibiotic-mediated microbiota depletion. Faecal microbiota transplantation from DNBS donors induced a long-lasting visceral hypersensitivity in control rats. Pain threshold trend correlated with major modifications in the composition of gut microbiota and short chain fatty acids. By contrast, no significant alterations of colon histology, permeability, and monoamines levels were detected. Finally, by manipulating the gut microbiota of DNBS-treated animals, a counteraction of persistent visceral pain was achieved. The present results provide novel insights into the relationship between intestinal microbiota and visceral hypersensitivity, highlighting the therapeutic potential of microbiota-targeted interventions.}, }
@article {pmid35435504, year = {2022}, author = {Deng, L and Wojciech, L and Png, CW and Koh, EY and Aung, TT and Kioh, DYQ and Chan, ECY and Malleret, B and Zhang, Y and Peng, G and Gascoigne, NRJ and Tan, KSW}, title = {Experimental colonization with Blastocystis ST4 is associated with protective immune responses and modulation of gut microbiome in a DSS-induced colitis mouse model.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {79}, number = {5}, pages = {245}, pmid = {35435504}, issn = {1420-9071}, support = {R-571-000-037-114//NUHS Seed Grant/ ; R-571-000-061-114//NUHS Seed Grant/ ; R-148-000-277-114//NUS Research Grant/ ; CPF2017-12//Chengdu Giant Panda Breeding Research Foundation/ ; }, abstract = {BACKGROUND: Blastocystis is a common gut protistan parasite in humans and animals worldwide, but its interrelationship with the host gut microbiota and mucosal immune responses remains poorly understood. Different murine models of Blastocystis colonization were used to examine the effect of a common Blastocystis subtype (ST4) on host gut microbial community and adaptive immune system.
RESULTS: Blastocystis ST4-colonized normal healthy mice and Rag1-/- mice asymptomatically and was able to alter the microbial community composition, mainly leading to increases in the proportion of Clostridia vadinBB60 group and Lachnospiraceae NK4A136 group, respectively. Blastocystis ST4 colonization promoted T helper 2 (Th2) response defined by interleukin (IL)-5 and IL-13 cytokine production, and T regulatory (Treg) induction from colonic lamina propria in normal healthy mice. Additionally, we observed that Blastocystis ST4 colonization can maintain the stability of bacterial community composition and induce Th2 and Treg immune responses to promote faster recovery from experimentally induced colitis. Furthermore, fecal microbiota transplantation of Blastocystis ST4-altered gut microbiome to colitis mice reduced the severity of colitis, which was associated with increased production of short-chain fat acids (SCFAs) and anti-inflammatory cytokine IL-10.
CONCLUSIONS: The data confirm our hypothesis that Blastocystis ST4 is a beneficial commensal, and the beneficial effects of Blastocystis ST4 colonization is mediated through modulating of the host gut bacterial composition, SCFAs production, and Th2 and Treg responses in different murine colonization models.}, }
@article {pmid35435140, year = {2022}, author = {Debédat, J and Le Roy, T and Voland, L and Belda, E and Alili, R and Adriouch, S and Bel Lassen, P and Kasahara, K and Hutchison, E and Genser, L and Torres, L and Gamblin, C and Rouault, C and Zucker, JD and Kapel, N and Poitou, C and Marcelin, G and Rey, FE and Aron-Wisnewsky, J and Clément, K}, title = {The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2050635}, doi = {10.1080/19490976.2022.2050635}, pmid = {35435140}, issn = {1949-0984}, abstract = {Roux-en-Y gastric bypass (RYGB) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes (T2D) improvements in patients with severe obesity and T2D. We hypothesized a causal implication of the gut microbiota (GM) in these metabolic benefits, as RYGB is known to deeply impact its composition. In a cohort of 100 patients with baseline T2D who underwent RYGB and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their T2D (Severe vs Mild) throughout the follow-up. We identified via nanopore-based GM sequencing that the more severe cases of unresolved T2D were associated with a major increase of the class Bacteroidia, including 12 species comprising Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals' metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.}, }
@article {pmid35432306, year = {2022}, author = {Jasiński, M and Biliński, J and Basak, GW}, title = {The Role of the Crosstalk Between Gut Microbiota and Immune Cells in the Pathogenesis and Treatment of Multiple Myeloma.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {853540}, doi = {10.3389/fimmu.2022.853540}, pmid = {35432306}, issn = {1664-3224}, abstract = {Around 10% of all hematologic malignancies are classified as multiple myeloma (MM), the second most common malignancy within that group. Although massive progress in developing of new drugs against MM has been made in recent years, MM is still an incurable disease, and every patient eventually has relapse refractory to any known treatment. That is why further and non-conventional research elucidating the role of new factors in MM pathogenesis is needed, facilitating discoveries of the new drugs. One of these factors is the gut microbiota, whose role in health and disease is still being explored. This review presents the continuous changes in the gut microbiota composition during our whole life with a particular focus on its impact on our immune system. Additionally, it mainly focuses on the chronic antigenic stimulation of B-cells as the leading mechanism responsible for MM promotion. The sophisticated interactions between microorganisms colonizing our gut, immune cells (dendritic cells, macrophages, neutrophils, T/B cells, plasma cells), and intestinal epithelial cells will be shown. That article summarizes the current knowledge about the initiation of MM cells, emphasizing the role of microorganisms in that process.}, }
@article {pmid35432269, year = {2022}, author = {Qu, L and Cheng, Q and Wang, Y and Mu, H and Zhang, Y}, title = {COPD and Gut-Lung Axis: How Microbiota and Host Inflammasome Influence COPD and Related Therapeutics.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {868086}, doi = {10.3389/fmicb.2022.868086}, pmid = {35432269}, issn = {1664-302X}, abstract = {The exact pathogenesis of chronic obstructive pulmonary disease (COPD) remains largely unknown. While current management strategies are effective at stabilizing the disease or relief the symptoms, new approaches are required to target underlying disease process and reverse lung function deterioration. Recent research showed that pneumonia bacteria is critical in disease progression and gut microbiome is likely perturbed in COPD, which is usually accompanied by a decreased intestinal microbial diversity and a disturbance in immune system, contributing to a chronic inflammation. The cross-talk between gut microbes and lungs, termed as the "gut-lung axis," is known to impact immune response and homeostasis in the airway. Although the gut and respiratory microbiota exhibit compositional differences, the gut and lung showed similarities in the origin of epithelia of both gastrointestinal and respiratory tracts, the anatomical structure, and early-life microbial colonization. Evidence showed that respiratory infection might be prevented, or at least dampened by regulating gut microbial ecosystem; thus, a promising yet understudied area of COPD management is nutrition-based preventive strategies. COPD patient is often deficient in nutrient such as antioxidant, vitamins, and fiber intake. However, further larger-scale randomized clinical trials (RCTs) are required to establish the role of these nutrition-based diet in COPD management. In this review, we highlight the important and complex interaction of microbiota and immune response on gut-lung axis. Further research into the modification and improvement of the gut microbiota and new interventions through diet, probiotics, vitamins, and fecal microbiota transplantation is extreme critical to provide new preventive therapies for COPD.}, }
@article {pmid35431512, year = {2022}, author = {Hong, Y and Zhao, J and Chen, YR and Huang, ZH and Hou, LD and Shen, B and Xin, Y}, title = {Spinal anesthesia alleviates dextran sodium sulfate-induced colitis by modulating the gut microbiota.}, journal = {World journal of gastroenterology}, volume = {28}, number = {12}, pages = {1239-1256}, doi = {10.3748/wjg.v28.i12.1239}, pmid = {35431512}, issn = {2219-2840}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease with recurrent intestinal inflammation. Although the exact etiology of IBD remains unknown, the accepted hypothesis of the pathogenesis to date is that abnormal immune responses to the gut microbiota are caused by environmental factors. The role of the gut microbiota, particularly the bidirectional interaction between the brain and gut microbiota, has gradually attracted more attention.
AIM: To investigate the potential effect of spinal anesthesia on dextran sodium sulfate (DSS)-induced colitis mice and to detect whether alterations in the gut microbiota would be crucial for IBD.
METHODS: A DSS-induced colitis mice model was established. Spinal anesthesia was administered on colitis mice in combination with the methods of cohousing and fecal microbiota transplantation (FMT) to explore the role of spinal anesthesia in IBD and identify the potential mechanisms involved.
RESULTS: We demonstrated that spinal anesthesia had protective effects against DSS-induced colitis by alleviating clinical symptoms, including reduced body weight loss, decreased disease activity index score, improved intestinal permeability and colonic morphology, decreased inflammatory response, and enhanced intestinal barrier functions. Moreover, spinal anesthesia significantly increased the abundance of Bacteroidetes, which was suppressed in the gut microbiota of colitis mice. Interestingly, cohousing with spinal anesthetic mice and FMT from spinal anesthetic mice can also alleviate DSS-induced colitis by upregulating the abundance of Bacteroidetes. We further showed that spinal anesthesia can reduce the increase in noradrenaline levels induced by DSS, which might affect the gut microbiota.
CONCLUSION: These data suggest that microbiota dysbiosis may contribute to IBD and provide evidence supporting the protective effects of spinal anesthesia on IBD by modulating the gut microbiota, which highlights a novel approach for the treatment of IBD.}, }
@article {pmid35430804, year = {2022}, author = {Xiao, W and Su, J and Gao, X and Yang, H and Weng, R and Ni, W and Gu, Y}, title = {The microbiota-gut-brain axis participates in chronic cerebral hypoperfusion by disrupting the metabolism of short-chain fatty acids.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {62}, pmid = {35430804}, issn = {2049-2618}, support = {82171313//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 81870917//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 81771237//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82101397//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 2016YFC1301704//Ministry of Human Resources and Social Security/ ; 2018SHZDZX01//Science and Technology Commission of Shanghai Municipality/ ; }, abstract = {BACKGROUND: Chronic cerebral hypoperfusion (CCH) underlies secondary brain injury following certain metabolic disorders and central nervous system (CNS) diseases. Dysregulation of the microbiota-gut-brain axis can exacerbate various CNS disorders through aberrantly expressed metabolites such as short-chain fatty acids (SCFAs). Yet, its relationship with CCH remains to be demonstrated. And if so, it is of interest to explore whether restoring gut microbiota to maintain SCFA metabolism could protect against CCH.
RESULTS: Rats subjected to bilateral common carotid artery occlusion (BCCAO) as a model of CCH exhibited cognitive impairment, depressive-like behaviors, decreased gut motility, and compromised gut barrier functions. The 16S ribosomal RNA gene sequencing revealed an abnormal gut microbiota profile and decreased relative abundance of some representative SCFA producers, with the decreased hippocampal SCFAs as the further evidence. Using fecal microbiota transplantation (FMT), rats recolonized with a balanced gut microbiome acquired a higher level of hippocampal SCFAs, as well as decreased neuroinflammation when exposed to lipopolysaccharide. Healthy FMT promoted gut motility and gut barrier functions, and improved cognitive decline and depressive-like behaviors by inhibiting hippocampal neuronal apoptosis in BCCAO rats. Long-term SCFA supplementation further confirmed its neuroprotective effect in terms of relieving inflammatory response and hippocampal neuronal apoptosis following BCCAO.
CONCLUSION: Our results demonstrate that modulating the gut microbiome via FMT can ameliorate BCCAO-induced gut dysbiosis, cognitive decline, and depressive-like behaviors, possibly by enhancing the relative abundance of SCFA-producing floras and subsequently increasing SCFA levels. Video abstract.}, }
@article {pmid35426646, year = {2022}, author = {Adams, SM and Close, ED and Shreenath, AP}, title = {Ulcerative Colitis: Rapid Evidence Review.}, journal = {American family physician}, volume = {105}, number = {4}, pages = {406-411}, pmid = {35426646}, issn = {1532-0650}, abstract = {Ulcerative colitis is a relapsing and remitting inflammatory bowel disease of the large intestine. Risk factors include recent Salmonella or Campylobacter infection and a family history of ulcerative colitis. Diagnosis is suspected based on symptoms of urgency, tenesmus, and hematochezia and is confirmed with endoscopic findings of continuous inflammation from the rectum to more proximal colon, depending on the extent of disease. Fecal calprotectin may be used to assess disease activity and relapse. Medications available to treat the inflammation include 5-aminosalicylic acid, corticosteroids, tumor necrosis factor-alpha antibodies, anti-integrin antibodies, anti-interleukin-12 and -23 antibodies, and Janus kinase inhibitors. Choice of medication and method of delivery depend on the location and severity of mucosal inflammation. Other treatments such as fecal microbiota transplantation are considered experimental, and complementary therapies such as probiotics and curcumin have mixed data. Surgical treatment may be needed for fulminant or refractory disease. Increased risk of colorectal cancer and use of immunosuppressive therapies affect the preventive care needs for these patients.}, }
@article {pmid35421334, year = {2022}, author = {Severyn, CJ}, title = {Find a little help from my (microbial) friends.}, journal = {Cell host & microbe}, volume = {30}, number = {4}, pages = {420-422}, doi = {10.1016/j.chom.2022.03.024}, pmid = {35421334}, issn = {1934-6069}, mesh = {*Clostridioides difficile ; *Clostridium Infections/prevention & control ; Fecal Microbiota Transplantation ; Friends ; Humans ; *Microbiota ; }, abstract = {Modulation of the microbiota to improve clinical outcomes remains challenging partially because of the large variability in biotherapeutic composition. In this issue of Cell Host & Microbe, Dsouza and colleagues present the phase 1 study results of a defined microbial consortia developed for the prevention of recurrent Clostridioides difficile infection (CDI).}, }
@article {pmid34797954, year = {2022}, author = {Cheng, J and Li, W and Wang, Y and Cao, Q and Ni, Y and Zhang, W and Guo, J and Chen, B and Zang, Y and Zhu, Y}, title = {Electroacupuncture modulates the intestinal microecology to improve intestinal motility in spinal cord injury rats.}, journal = {Microbial biotechnology}, volume = {15}, number = {3}, pages = {862-873}, pmid = {34797954}, issn = {1751-7915}, mesh = {Animals ; *Electroacupuncture ; Fecal Microbiota Transplantation ; Gastrointestinal Motility ; Rats ; Serotonin ; *Spinal Cord Injuries/metabolism/pathology/therapy ; }, abstract = {Spinal cord injury (SCI) is a disease involving gastrointestinal disorders. The underlying mechanisms of the potential protective effects of electroacupuncture (EA) and 5-hydroxytryptamine (5-HT) system on SCI remain unknown. We investigated whether EA improves gut microbial dysbiosis in SCI and regulates the 5-HT system. 16S rDNA gene sequencing was applied to investigate alterations in the gut microbiome of the rats. Faecal metabolites and the expression of the 5-HT system were detected. EA and faecal microbiota transplantation (FMT) treatment facilitated intestinal transmission functional recovery and restored the colon morphology of SCI rats. The composition of the intestinal microbiota, including numbers of phylum Proteobacteria, class Clostridia, order Bacteroidales, and genus Dorea, were amplified in SCI rats, and EA and FMT significantly reshaped the intestinal microbiota. SCI resulted in disturbed metabolic conditions in rats, and the EA and FMT group showed increased amounts of catechin compared with SCI rats. SCI inhibited 5-HT system expression in the colon, which was significantly reversed by EA and FMT treatment. Therefore, EA may ameliorate SCI by modulating microbiota and metabolites and regulate the 5-HT system. Our study provides new insights into the pathogenesis and therapy of SCI from the perspective of microbiota and 5-HT regulation.}, }
@article {pmid35421353, year = {2022}, author = {Dsouza, M and Menon, R and Crossette, E and Bhattarai, SK and Schneider, J and Kim, YG and Reddy, S and Caballero, S and Felix, C and Cornacchione, L and Hendrickson, J and Watson, AR and Minot, SS and Greenfield, N and Schopf, L and Szabady, R and Patarroyo, J and Smith, W and Harrison, P and Kuijper, EJ and Kelly, CP and Olle, B and Bobilev, D and Silber, JL and Bucci, V and Roberts, B and Faith, J and Norman, JM}, title = {Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers.}, journal = {Cell host & microbe}, volume = {30}, number = {4}, pages = {583-598.e8}, doi = {10.1016/j.chom.2022.03.016}, pmid = {35421353}, issn = {1934-6069}, abstract = {Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and clinical efficacy. Live biotherapeutic products (LBPs) consisting of defined consortia of clonal bacterial isolates have been proposed as an alternative therapeutic class because of their promising preclinical results and safety profile. We describe VE303, an LBP comprising 8 commensal Clostridia strains under development for rCDI, and its early clinical development in healthy volunteers (HVs). In a phase 1a/b study in HVs, VE303 is determined to be safe and well-tolerated at all doses tested. VE303 strains optimally colonize HVs if dosed over multiple days after vancomycin pretreatment. VE303 promotes the establishment of a microbiota community known to provide colonization resistance.}, }
@article {pmid35421277, year = {2022}, author = {Asadi, A and Shadab Mehr, N and Mohamadi, MH and Shokri, F and Heidary, M and Sadeghifard, N and Khoshnood, S}, title = {Obesity and gut-microbiota-brain axis: A narrative review.}, journal = {Journal of clinical laboratory analysis}, volume = {}, number = {}, pages = {e24420}, doi = {10.1002/jcla.24420}, pmid = {35421277}, issn = {1098-2825}, abstract = {INTRODUCTION: Obesity is a major health problem that is associated with many physiological and mental disorders, such as diabetes, stroke, and depression. Gut microbiota has been affirmed to interact with various organs, including the brain. Intestinal microbiota and their metabolites might target the brain directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms, and they can regulate metabolism, adiposity, homoeostasis and energy balance, and central appetite and food reward signaling, which together have crucial roles in obesity. Studies support the concept of bidirectional signaling within the gut-brain axis (GBA) in the pathophysiology of obesity, mediated by metabolic, endocrine, neural, and immune system mechanisms.
MATERIALS AND METHODS: Scopus, PubMed, Google Scholar, and Web of Science databases were searched to find relevant studies.
RESULTS: The gut-brain axis (GBA), a bidirectional connection between the gut microbiota and brain, influences physiological function and behavior through three different pathways. Neural pathway mainly consists of the enteric nervous system (ENS) and vagus nerve. Endocrine pathway, however, affects the neuroendocrine system of the brain, particularly the hypothalamus-pituitary-adrenal (HPA) axis and immunological pathway. Several alterations in the gut microbiome can lead to obesity, by modulating metabolic pathways and eating behaviors of the host through GBA. Therefore, novel therapies targeting the gut microbiome, i.e., fecal microbiota transplantation and supplementation with probiotics and prebiotics, can be a potential treatment for obesity.
CONCLUSION: This study corroborates the effect of gut microbiome on physiological function and body weight. The results show that the gut microbiota is becoming a target for new antiobesity therapies.}, }
@article {pmid35418976, year = {2022}, author = {Wang, J and Zhang, H and He, J and Xiong, X}, title = {The Role of the Gut Microbiota in the Development of Ischemic Stroke.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {845243}, doi = {10.3389/fimmu.2022.845243}, pmid = {35418976}, issn = {1664-3224}, abstract = {An increasing number of studies have focused on the gut microbiota and its relationship with various neurological diseases. The gut microbiota can affect the metabolic status of the body, in addition to having an important impact on blood pressure, blood glucose, and atherosclerosis, all of which are risk factors for ischemic stroke. In this review, we summarized studies that included the physiological function of the gut microbiota and gut microbiota disorders related to the central nervous system, thus providing novel ideas for the prevention and treatment of ischemic stroke.}, }
@article {pmid35409202, year = {2022}, author = {Bastos, RMC and Simplício-Filho, A and Sávio-Silva, C and Oliveira, LFV and Cruz, GNF and Sousa, EH and Noronha, IL and Mangueira, CLP and Quaglierini-Ribeiro, H and Josefi-Rocha, GR and Rangel, ÉB}, title = {Fecal Microbiota Transplant in a Pre-Clinical Model of Type 2 Diabetes Mellitus, Obesity and Diabetic Kidney Disease.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, doi = {10.3390/ijms23073842}, pmid = {35409202}, issn = {1422-0067}, support = {2013/19560-6; 2017/23195-2; 2017/18072-9; 2016/26263-6//São Paulo Research Foundation/ ; 2016-5/423320//National Council for Scientific and Technological Development/ ; 2015//European Foundation for the Study of Diabetes/Sanofi/ ; }, abstract = {Diabetes mellitus (DM) burden encompasses diabetic kidney disease (DKD), the leading cause of end-stage renal disease worldwide. Despite compelling evidence indicating that pharmacological intervention curtails DKD progression, the search for non-pharmacological strategies can identify novel targets for drug development against metabolic diseases. One of those emergent strategies comprises the modulation of the intestinal microbiota through fecal transplant from healthy donors. This study sought to investigate the benefits of fecal microbiota transplant (FMT) on functional and morphological parameters in a preclinical model of type 2 DM, obesity, and DKD using BTBRob/ob mice. These animals develop hyperglycemia and albuminuria in a time-dependent manner, mimicking DKD in humans. Our main findings unveiled that FMT prevented body weight gain, reduced albuminuria and tumor necrosis factor-α (TNF-α) levels within the ileum and ascending colon, and potentially ameliorated insulin resistance in BTBRob/ob mice. Intestinal structural integrity was maintained. Notably, FMT was associated with the abundance of the succinate-consuming Odoribacteraceae bacteria family throughout the intestine. Collectively, our data pointed out the safety and efficacy of FMT in a preclinical model of type 2 DM, obesity, and DKD. These findings provide a basis for translational research on intestinal microbiota modulation and testing its therapeutic potential combined with current treatment for DM.}, }
@article {pmid35402293, year = {2022}, author = {Ding, D and Yong, H and You, N and Lu, W and Yang, X and Ye, X and Wang, Y and Cai, T and Zheng, X and Chen, H and Cui, B and Zhang, F and Liu, X and Mao, JH and Lu, Y and Chang, H}, title = {Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {820367}, doi = {10.3389/fcimb.2022.820367}, pmid = {35402293}, issn = {2235-2988}, mesh = {*Diabetes Mellitus, Type 2/therapy ; *Fecal Microbiota Transplantation ; Feces ; Glycated Hemoglobin A ; Humans ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {Background: Increasing evidence shows that alterations in gut microbiome (GM) contribute to the development of type 2 diabetes mellitus (T2DM), and fecal microbiota transplantation (FMT) successfully treats various human diseases. However, the benefits of FMT therapy to T2DM patients remain unknown.
Methods: We enrolled 17 patients with T2DM for nonblinded, one-armed intervention trial of FMT. A total of 20 healthy individuals were recruited as the baseline control. HbA1c% and metabolic parameter change were evaluated in 17 T2DM patients 12 weeks after they received FMT from healthy donors. The GM composition was characterized by 16S rRNA gene amplicon sequencing from fecal samples prior to and 12 weeks after FMT treatment.
Results: We found that the GM of T2DM patients was reconstituted by FMT. We observed a statistically significant decrease in HbA1c% (from 7.565 ± 0.148 to 7.190 ± 0.210, p<0.01), blood glucose (from 8.483 ± 0.497 to 7.286 ± 0.454 mmol/L, p<0.01), and uric acid (from 309.4 ± 21.5 to 259.1 ± 15.8 µmol/L, p<0.01) while a significant increase in postprandial C-peptide (from 4.503 ± 0.600 to 5.471 ± 0.728 ng/ml, p<0.01) at 12 weeks after FMT. Closely evaluating the changes in these assays, we found individual variability in response to FMT treatment. Out of 17 T2DM patients, 11 were found to significantly improve T2DM symptoms. The FMT responders have significantly higher levels of the family Rikenellaceae and the genus Anaerotruncus (family Ruminococcaceae) in their pretreated fecal in comparison to nonresponders, which could predict the clinical response with an area under the curve of 0.83.
Conclusion: Our findings suggest that certain T2DM patients can potentially benefit from FMT, and the pretreated abundance of Rikenellaceae and Anaerotruncus in the fecal of patients may serve as potential biomarkers for selecting T2DM patients to receive FMT.}, }
@article {pmid35401492, year = {2022}, author = {Gao, JM and Rao, JH and Wei, ZY and Xia, SY and Huang, L and Tang, MT and Hide, G and Zheng, TT and Li, JH and Zhao, GA and Sun, YX and Chen, JH}, title = {Transplantation of Gut Microbiota From High-Fat-Diet-Tolerant Cynomolgus Monkeys Alleviates Hyperlipidemia and Hepatic Steatosis in Rats.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {876043}, doi = {10.3389/fmicb.2022.876043}, pmid = {35401492}, issn = {1664-302X}, abstract = {Emerging evidence has been reported to support the involvement of the gut microbiota in the host's blood lipid and hyperlipidemia (HLP). However, there remains unexplained variation in the host's blood lipid phenotype. Herein a nonhuman primate HLP model was established in cynomolgus monkeys fed a high-fat diet (HFD) for 19 months. At month 19%, 60% (3/5) of the HFD monkeys developed HLP, but surprisingly 40% of them (2/5) exhibited strong tolerance to the HFD (HFD-T) with their blood lipid profiles returning to normal levels. Metagenomic analysis was used to investigate the compositional changes in the gut microbiota in these monkeys. Furthermore, the relative abundance of Megasphaera remarkably increased and became the dominant gut microbe in HFD-T monkeys. A validation experiment showed that transplantation of fecal microbiota from HFD-T monkeys reduced the blood lipid levels and hepatic steatosis in HLP rats. Furthermore, the relative abundance of Megasphaera significantly increased in rats receiving transplantation, confirming the successful colonization of the microbe in the host and its correlation with the change of the host's blood lipid profiles. Our results thus suggested a potentially pivotal lipid-lowering role of Megasphaera in the gut microbiota, which could contribute to the variation in the host's blood lipid phenotype.}, }
@article {pmid35400819, year = {2022}, author = {Fukushima, S and Shiotani, A and Matsumoto, H and Handa, O and Handa, Y and Osawa, M and Murao, T and Umegaki, E and Kawano, M and Inoue, R and Naito, Y}, title = {Comparison of mucosa-associated microbiota in Crohn's disease patients with and without anti-tumor necrosis factor-α therapy.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {70}, number = {2}, pages = {182-188}, doi = {10.3164/jcbn.21-41}, pmid = {35400819}, issn = {0912-0009}, abstract = {Most studies on the gut microbiome of Crohn's disease have been conducted using feces, instead of intestinal mucus to analyze the mucosa-associated microbiota. To investigate the characteristics of mucosa-associated microbiota in Crohn's disease patients and the effect of anti-tumor necrosis factor (TNF)-α therapy on mucosa-associated microbiota, we analyzed microbiota in Crohn's disease patients using brushing samples taken from terminal ileum. The recruited subjects were 18 Crohn's disease patients and 13 controls. There were 10 patients with anti-TNF-α therapy in Crohn's disease group. Crohn's disease patients had significantly reduced α-diversity in Shannon index compared to the controls. The comparative analysis of the taxonomic composition at the genus level between the Crohn's disease group and the controls indicated that butyrate-producing bacteria were less abundant in the Crohn's disease group compared to the controls. There were no differences in the diversity between the patients taking anti-TNF-α therapy and the patients without. The comparative analysis of the taxonomic composition at the genus level between the two groups indicated that some of anti-inflammatory bacteria were less abundant in the anti-TNF-α therapy group than the other. Reduction of specific bacteria producing anti-inflammatory molecules, especially butyrate-producing bacteria may play important roles in the pathophysiology of Crohn's disease.}, }
@article {pmid35399688, year = {2022}, author = {He, Z and Ma, Y and Chen, X and Liu, S and Xiao, J and Wang, Y and Wang, W and Yang, H and Li, S and Cao, Z}, title = {Protective Effects of Intestinal Gallic Acid in Neonatal Dairy Calves Against Extended-Spectrum β-lactamase Producing Enteroaggregative Escherichia coli Infection: Modulating Intestinal Homeostasis and Colitis.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {864080}, doi = {10.3389/fnut.2022.864080}, pmid = {35399688}, issn = {2296-861X}, abstract = {Calf diarrhea induced by enteroaggregative E. coli (EAEC) spreads fast among young ruminants, causing continuous hazard to dairy industry. Antimicrobial drug abuse aggravates the incidence rate of multi-drug resistant (MDR) extended-spectrum β-lactamase-producing E. coli (ESBL-EC). However, knowledge of detection and significance of disease-related biomarkers in neonatal female calves are still limited. Gallic acid (GA), a natural secondary metabolite mostly derived from plants, has attracted increasing attention for its excellent anti-inflammatory and anti-oxidative properties. However, it is vague how GA engenders amelioration effects on clinical symptoms and colitis induced by ESBL-EAEC infection in neonatal animals. Here, differentiated gut microbiome and fecal metabolome discerned from neonatal calves were analyzed to ascertain biomarkers in their early lives. Commensal Collinsella and Coriobacterium acted as key microbial markers mediating colonization resistance. In addition, there exists a strongly positive relation between GA, short-chain fatty acid (SCFA) or other prebiotics, and those commensals using random forest machine learning algorithm and Spearman correlation analyses. The protective effect of GA pretreatment on bacterial growth, cell adherence, and ESBL-EAEC-lipopolysaccharide (LPS)-treated Caco-2 cells were first assessed, and results revealed direct antibacterial effects and diminished colonic cell inflammation. Then, oral GA mediated colitis attenuation and recovery of colonic short-chain fatty acid (SCFA) productions on neonatal mice peritonitis sepsis or oral infection model. To corroborate this phenomenon, fecal microbiota transplantation (FMT) method was adopted to remedy the bacterial infection. Of note, FMT from GA-treated neonatal mice achieved profound remission of clinical symptoms and colitis over the other groups as demonstrated by antibacterial capability and prominent anti-inflammatory abilities, revealing improved hindgut microbiota structure with enriched Clostridia_UCG-014, Lachnospiraceae, Oscillospiraceae, and Enterococcaceae, and upregulation of SCFA productions. Collectively, our findings provided the direct evidence of hindgut microbiota and intestinal metabolites, discriminating the health status of neonatal calves post ESBL-EAEC infection. The data provided novel insights into GA-mediated remission of colitis via amelioration of hindgut commensal structure and upregulation of SCFA productions. In addition, its eminent role as potential antibiotic alternative or synergist for future clinic ESBL-EAEC control in livestock.}, }
@article {pmid35399089, year = {2022}, author = {Wang, X and Tsai, T and Zuo, B and Wei, X and Deng, F and Li, Y and Maxwell, CV and Yang, H and Xiao, Y and Zhao, J}, title = {Donor age and body weight determine the effects of fecal microbiota transplantation on growth performance, and fecal microbiota development in recipient pigs.}, journal = {Journal of animal science and biotechnology}, volume = {13}, number = {1}, pages = {49}, pmid = {35399089}, issn = {1674-9782}, support = {2018-67015-27479//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: The application of fecal microbiota transplantation (FMT) to improve swine growth performance has been sporadically studied. Most of these studies used a single microbiota source and thus the effect of donor characteristics on recipient pigs' fecal microbiota development and growth performance is largely unknown.
RESULTS: In this study, we collected feces from six donors with heavy (H) or light (L) body weight and different ages (d 42, nursery; d 96, growing; and d 170, finisher) to evaluate their effects on the growth performance and fecal microbiota development of recipient pigs. Generally, recipients that received two doses of FMT from nursery and finisher stages donor at weaning (21 ± 2 days of age) inherited the donor's growth pattern, while the pigs gavaged with grower stage material exerted a numerically greater weight gain than the control pigs regardless of donor BW. FMT from heavier donors (NH, GH, and FH) led to the recipients to have numerically increased growth compared to their lighter counterparts (NL, GL, and FL, respectively) throughout the growing and most finishing stages. This benefit could be attributed to the enrichment of ASV25 Faecalibacterium, ASV61 Faecalibacterium, ASV438 Coriobacteriaceae_unclassified, ASV144 Bulleidia, and ASV129 Oribacterium and decrease of ASV13 Escherichia during nursery stage. Fecal microbiota transplantation from growing and finishing donors influenced the microbial community significantly in recipient pigs during the nursery stage. FMT of older donors' gut microbiota expedited recipients' microbiota maturity on d 35 and 49, indicated by increased estimated microbiota ages. The age-associated bacterial taxa included ASV206 Ruminococcaceae, ASV211 Butyrivibrio, ASV416 Bacteroides, ASV2 Streptococcus, and ASV291 Veillonellaceae. The body weight differences between GL and GH pigs on d 104 were associated with the increased synthesis of the essential amino acid, lysine and methionine, mixed acid fermentation, expedited glycolysis, and sucrose/galactose degradation.
CONCLUSIONS: Overall, our study provided insights into how donor age and body weight affect FMT outcomes regarding growth performance, microbiota community shifts, and lower GI tract metabolic potentials. This study also provided guidance to select qualified donors for future fecal microbiota transplantation.}, }
@article {pmid35398345, year = {2022}, author = {Osman, M and Budree, S and Kelly, CR and Panchal, P and Allegretti, JR and Kassam, Z and , and Olesen, SW and Ramakrishna, B and Dubois, N and O'Brien, K and Fischer, M and Stollman, N and Hays, RA and Kelly, CP and Amaratunga, K and Qazi, T and Crothers, JW and Abend, A and Bougas, M and Burns, L and Decaille-Hodge, I and Dickens, M and Edelstein, C and Gabdrakhmanova, D and Landry, R and Ling, K and Martin, D and Medina, G and Mendolia, G and Muñoz, R and Rao, S and Seng, M and Smith, M and Stehler, L and Yoder, K and Zellmer, C}, title = {Effectiveness and safety of fecal microbiota transplantation for Clostridioides difficile infection: Results from a 5,344 patient cohort study.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2022.03.051}, pmid = {35398345}, issn = {1528-0012}, }
@article {pmid35276080, year = {2022}, author = {Lam, S and Bai, X and Shkoporov, AN and Park, H and Wu, X and Lan, P and Zuo, T}, title = {Roles of the gut virome and mycobiome in faecal microbiota transplantation.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {7}, number = {5}, pages = {472-484}, doi = {10.1016/S2468-1253(21)00303-4}, pmid = {35276080}, issn = {2468-1253}, mesh = {Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; *Mycobiome ; Virome ; }, abstract = {Faecal microbiota transplantation (FMT) is an innovative approach to treat diseases that are associated with gut dysbiosis, by transferring a healthy stool microbiota to a recipient with disease. Beyond the bacteriome, the human gut also harbours diverse communities of viruses and fungi, collectively known as the virome and the mycobiome. The effect of the virome and the mycobiome on the success of FMT therapy has not been appreciated until recently. In this Review, we summarise the current literature on the effects of the gut virome and mycobiome on the treatment of various diseases with FMT. We discuss the beneficial effects and health concerns of viral and fungal transfer during FMT, and highlight the roles of bacteriophages and Candida species in FMT efficacy. We also summarise the intricate relationships between the gut virome, mycobiome, bacteriome, and host immunity underlying FMT effectiveness. Future efforts should be devoted to understanding the versatile roles and the therapeutic mechanisms of viral and fungal lineages, and their combinations, in different diseases. Harnessing the gut virome, mycobiome, and bacteriome in combination is a promising prospect for the future of FMT and microbiota-based therapies.}, }
@article {pmid35393390, year = {2022}, author = {Segovia-Rodríguez, L and Echeverry-Alzate, V and Rincón-Pérez, I and Calleja-Conde, J and Bühler, KM and Giné, E and Albert, J and Hinojosa, JA and Huertas, E and Gómez-Gallego, F and Bressa, C and Rodríguez de Fonseca, F and López-Moreno, JA}, title = {Gut microbiota and voluntary alcohol consumption.}, journal = {Translational psychiatry}, volume = {12}, number = {1}, pages = {146}, pmid = {35393390}, issn = {2158-3188}, abstract = {Alcohol is part of the usual diet of millions of individuals worldwide. However, not all individuals who drink alcohol experience the same effects, nor will everyone develop an alcohol use disorder. Here we propose that the intestinal microbiota (IMB) helps explain the different consumption patterns of alcohol among individuals. 507 humans participated in this study and alcohol consumption and IMB composition were analyzed. On the other hand, in 80 adult male Wistar rats, behavioral tests, alcohol intoxication, fecal transplantation, administration of antibiotics and collection of fecal samples were performed. For identification and relative quantification of bacterial taxa was used the bacterial 16 S ribosomal RNA gene. In humans, we found that heavy episodic drinking is associated with a specific stool type phenotype (type 1, according to Bristol Stool Scale; p < 0.05) and with an increase in the abundance of Actinobacteria (p < 0.05). Next, using rats, we demonstrate that the transfer of IMB from alcohol-intoxicated animals causes an increase in voluntary alcohol consumption in transplant-recipient animals (p < 0.001). The relative quantification data indicate that the genus Porphyromonas could be associated with the effect on voluntary alcohol consumption. We also show that gut microbiota depletion by antibiotics administration causes a reduction in alcohol consumption (p < 0.001) and altered the relative abundance of relevant phyla such as Firmicutes, Bacteroidetes or Cyanobacteria (p < 0.05), among others. Benjamini-Hochberg false discovery rate (FDR) correction was performed for multiple comparisons. These studies reveal some of the consequences of alcohol on the IMB and provide evidence that manipulation of IMB may alter voluntary alcohol consumption.}, }
@article {pmid35387830, year = {2022}, author = {Pérez-Nadales, E and Cano, Á and Recio, M and Artacho, MJ and Guzmán-Puche, J and Doblas, A and Vidal, E and Natera, C and Martínez-Martínez, L and Torre-Cisneros, J and Castón, JJ}, title = {Randomised, double-blind, placebo-controlled, phase 2, superiority trial to demonstrate the effectiveness of faecal microbiota transplantation for selective intestinal decolonisation of patients colonised by carbapenemase-producing Klebsiella pneumoniae (KAPEDIS).}, journal = {BMJ open}, volume = {12}, number = {4}, pages = {e058124}, doi = {10.1136/bmjopen-2021-058124}, pmid = {35387830}, issn = {2044-6055}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Proteins ; *Carbapenem-Resistant Enterobacteriaceae ; Fecal Microbiota Transplantation/methods ; Humans ; *Klebsiella Infections/drug therapy ; Klebsiella pneumoniae ; beta-Lactamases ; }, abstract = {INTRODUCTION: Infections caused by carbapenemase-producing Enterobacterales are frequent and associated with high rates of mortality. Intestinal carriers are at increased risk of infection by these microorganisms. Decolonisation strategies with antibiotics have not obtained conclusive results. Faecal microbiota transplantation (FMT) could be an effective and safe strategy to decolonise intestinal carriers of KPC-producing Klebsiella pneumoniae (KPC-Kp) but this hypothesis needs evaluation in appropriate clinical trials.
METHODS AND ANALYSIS: The KAPEDIS trial is a single-centre, randomised, double-blind, placebo-controlled, phase 2, superiority clinical trial of FMT for eradication of intestinal colonisation by KPC-Kp. One hundred and twenty patients with rectal colonisation by KPC-Kp will be randomised 1:1 to receive encapsulated lyophilised FMT or placebo. The primary outcome is KPC-Kp eradication at 30 days. Secondary outcomes are: (1) frequency of adverse events; (2) changes in KPC-Kp relative load within the intestinal microbiota at 7, 30 and 90 days, estimated by real-time quantitative PCR analysis of rectal swab samples and (3) rates of persistent eradication, KPC-Kp infection and crude mortality at 90 days. Participants will be monitored for adverse effects throughout the intervention.
ETHICS AND DISSEMINATION: Ethical approval was obtained from Reina Sofía University Hospital Institutional Review Board (approval reference number: 2019-003808-13). Trial results will be published in peer-reviewed journals and disseminated at national and international conferences.
TRIAL REGISTRATION NUMBER: NCT04760665.}, }
@article {pmid35159245, year = {2022}, author = {Cold, F and Svensson, CK and Petersen, AM and Hansen, LH and Helms, M}, title = {Long-Term Safety Following Faecal Microbiota Transplantation as a Treatment for Recurrent Clostridioides difficile Infection Compared with Patients Treated with a Fixed Bacterial Mixture: Results from a Retrospective Cohort Study.}, journal = {Cells}, volume = {11}, number = {3}, pages = {}, pmid = {35159245}, issn = {2073-4409}, support = {7076-00129B//Danish Innovation Fund/ ; }, mesh = {*Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces/microbiology ; Humans ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) is the recommended treatment for recurrent C. difficile infection (rCDI) following a second recurrence. FMT is considered safe in the short term when procedures for the screening of donors and transferred material are followed. However, the long-term safety profile of FMT treatment is largely unknown. In a retrospective cohort study, we assessed the long-term safety of patients treated for rCDI with FMT or a fixed bacterial mixture, rectal bacteriotherapy (RBT). The overall survival, risk of hospital admission, onset of certain pre-specified diseases (cancer, diabetes mellitus, hypertension and inflammatory bowel disease) and risk of being diagnosed with a multidrug-resistant organism were assessed by undertaking a review of the treated patients' medical records for up to five years following treatment. A total of 280 patients were treated for rCDI with FMT (n = 145) or RBT (n = 135) between 2016 and 2020. In the five years following treatment, there were no differences in survival (adjusted hazard ratio (aHR) 1.03; 95% CI 0.68-1.56), p = 0.89), risk of hospital admission ((aHR 0.92; 95% CI 0.72-1.18), p = 0.5) or onset of any of the analysed diseases. In conclusion, FMT was not associated with increased mortality, risk of hospital admission or onset of disease following treatment when compared with RBT.}, }
@article {pmid35390687, year = {2022}, author = {Huang, C and Wu, D and Zhang, K and Khan, FA and Pandupuspitasari, NS and Wang, Y and Huo, L and Sun, F}, title = {Perfluorooctanoic acid alters the developmental trajectory of female germ cells and embryos in rodents and its potential mechanism.}, journal = {Ecotoxicology and environmental safety}, volume = {236}, number = {}, pages = {113467}, doi = {10.1016/j.ecoenv.2022.113467}, pmid = {35390687}, issn = {1090-2414}, abstract = {The epidemiological studies regarding perfluorooctanoic acid (PFOA) suggests that its exposure causes reproductive health issues, the underlying mechanisms of which are still in its infancy. Here, we report that PFOA deteriorates female reproduction at multiple development stages. Oocyte meiosis and preimplantation development are severely impaired by PFOA with oxidative stress being a contributor. Supplementing with antioxidant melatonin partially rescues oocyte meiotic maturation and non-apoptotic demise. The attenuation in ovarian follicle development however can be improved by metformin but not melatonin. Importantly, metformin blunts PFOA-induced fetal growth retardation (FGR) and such protective effect could be recapitulated by transplantation of fecal material and pharmacological activation of AMPK. Mechanistically, PFOA causes gut microbiota dysbiosis, which might thereby rewire host metabolism of L-phenylalanine, histamine and L-palmitoylcarnitine that triggers hyperphenylalaninaemia, inflammation and ferroptosis to initiate FGR. Deregulated serine metabolism by the gut microbe constitutes an alternative mechanism underlying PFOA-induced FGR in that modulation of serine in dam's diet phenocopied the FGR. Our study expands the understanding of risk factors that impair human reproductive health, and proposes restoration of gut microbiota diversity and intervention of metabolism as therapeutics mitigating health risks predisposed by environmental perturbation.}, }
@article {pmid35388189, year = {2022}, author = {Aggarwala, V and Mogno, I and Li, Z and Yang, C and Britton, GJ and Chen-Liaw, A and Mitcham, J and Bongers, G and Gevers, D and Clemente, JC and Colombel, JF and Grinspan, A and Faith, J}, title = {Author Correction: Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41564-022-01118-8}, pmid = {35388189}, issn = {2058-5276}, support = {650451//Crohn's and Colitis Foundation (Crohn's & Colitis Foundation)/ ; 580924//Crohn's and Colitis Foundation (Crohn's & Colitis Foundation)/ ; }, }
@article {pmid35387936, year = {2022}, author = {Tamura, S and Ishida, H and Shimizu, T and Imaeda, H and Nishida, A and Bamba, S and Andoh, A and Iwasa, Y and Kuroda, H}, title = {[Fecal microbiota transplantation for refractory Clostridioides difficile infection with Crohn's disease in an allogeneic bone marrow transplant recipient].}, journal = {[Rinsho ketsueki] The Japanese journal of clinical hematology}, volume = {63}, number = {3}, pages = {217-223}, doi = {10.11406/rinketsu.63.217}, pmid = {35387936}, issn = {0485-1439}, abstract = {We report a case of a 15-year-old girl who developed refractory Clostridioides difficile infection (CDI) after allogeneic bone marrow transplantation (BMT). She was treated successfully with fecal microbiota transplantation (FMT). The patient who had aplastic anemia underwent allogeneic BMT from an HLA 1-locus-mismatched unrelated donor. Four months later, she developed gastrointestinal graft-versus-host disease (GVHD), and immunosuppressive treatment improved the GVHD. However, she developed CDI 5 months after BMT and experienced recurrence after that. Fifteen months after transplant, CDI relapsed despite discontinuation of immunosuppressive treatment; thus, she underwent FMT. Colonoscopy at the time of FMT revealed round aphthae, mainly in the ileocecum, and colonic biopsy revealed inflammatory cell infiltration and noncaseating epithelioid granuloma, which fulfilled the diagnostic criteria for Crohn's disease. Following FMT for CDI, she was treated with enteric budesonide and intravenous methotrexate for Crohn's disease. These interventions resulted in a marked improvement in both CDI and Crohn's disease. Twenty-eight months after FMT, both CDI and Crohn's disease remained in remission with oral mesalamine monotherapy.}, }
@article {pmid35386224, year = {2022}, author = {Zhang, H and Xu, J and Wu, Q and Fang, H and Shao, X and Ouyang, X and He, Z and Deng, Y and Chen, C}, title = {Gut Microbiota Mediates the Susceptibility of Mice to Sepsis-Associated Encephalopathy by Butyric Acid.}, journal = {Journal of inflammation research}, volume = {15}, number = {}, pages = {2103-2119}, doi = {10.2147/JIR.S350566}, pmid = {35386224}, issn = {1178-7031}, abstract = {Purpose: Neuroinflammation plays an important part in the pathophysiology of sepsis-associated encephalopathy (SAE). Gut microbiota and gut brain axis are considered as important mediators in the development of neurological diseases. The aim of this study was to investigate the role of intestinal microbiota in sepsis-related brain injury and to explore the underlying mechanisms.
Methods: Mouse model of SAE was established using cecal ligation and puncture (CLP). Based on the mouse mortality and the associated time of death, light SAE (LSAE) and severe SAE (SSAE) were classified. Fecal microbiota transplantation (FMT) was performed to verify the role of intestinal microbiota. Feces of mice in the two groups which collected before operation were sequenced for 16S and targeted short chain fatty acids.
Results: Intestinal microbiota from SSAE and LSAE mice displayed diverse functions. Interestingly, LSAE mice produced more butyric acid compared with SSAE mice. In the in vivo experiments, sodium butyrate (NaB) reduced the high oxidative stress levels in mice hippocampus and conferred a marked survival superiority to sepsis mice. In addition, NaB prevented the increase in intracellular reactive oxygen species (ROS) generation and inducible nitric-oxide synthase expression in LPS-stimulated primary microglia. The GPR109A/Nrf2/HO-1 signaling pathway was found to be involved in the activation of antioxidant response of primary microglia induced by sodium butyrate.
Conclusion: Our findings indicate a crucial role of gut microbiota in the susceptibility to SAE. Butyrate, a metabolite of intestinal microbiota, may have a neuroprotective effect in the process of sepsis by GPR109A/Nrf2/HO-1 pathway.}, }
@article {pmid35084496, year = {2022}, author = {Stapleton, TE and Kohl, KD and Dearing, MD}, title = {Plant secondary compound- and antibiotic-induced community disturbances improve the establishment of foreign gut microbiota.}, journal = {FEMS microbiology ecology}, volume = {98}, number = {1}, pages = {}, doi = {10.1093/femsec/fiac005}, pmid = {35084496}, issn = {1574-6941}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Fecal transplants are a powerful tool for manipulating the gut microbial community, but how these non-native communities establish in the presence of an intact host gut microbiome is poorly understood. We explored the microbiome of desert woodrats (Neotoma lepida) to determine whether disrupting existing microbial communities using plant secondary compounds (PSCs) or antibiotics increases the establishment of foreign microbes. We administered two fecal transplants between natural populations of adult woodrats that harbor distinct gut microbiota and have different natural dietary exposure to PSCs. First, we administered fecal transplants to recipients given creosote resin, a toxin found in the natural diet of our "donor" population, and compared the gut microbial communities to animals given fecal transplants and control diet using 16S rRNA gene sequencing. Second, we disrupted the gut microbial community of the same recipients with an antibiotic prior to fecal transplants. We found that gut microbial communities of woodrats disrupted with PSCs or antibiotics resembled that of donors more closely than control groups. PSC treatment also enriched microbes associated with metabolizing dietary toxins in transplant recipients. These results demonstrate that microbial community disturbances by PSCs or antibiotics are sufficient to facilitate establishment of foreign microbes in animals with intact microbiomes.}, }
@article {pmid34896249, year = {2022}, author = {Kang, Y and Kang, X and Yang, H and Liu, H and Yang, X and Liu, Q and Tian, H and Xue, Y and Ren, P and Kuang, X and Cai, Y and Tong, M and Li, L and Fan, W}, title = {Lactobacillus acidophilus ameliorates obesity in mice through modulation of gut microbiota dysbiosis and intestinal permeability.}, journal = {Pharmacological research}, volume = {175}, number = {}, pages = {106020}, doi = {10.1016/j.phrs.2021.106020}, pmid = {34896249}, issn = {1096-1186}, mesh = {Adipose Tissue, Brown ; Animals ; Endotoxemia/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Gene Expression ; Insulin Resistance ; Intestinal Mucosa/metabolism ; *Lactobacillus acidophilus ; Lipid Metabolism/genetics ; Male ; Mice, Inbred C57BL ; Obesity/metabolism/microbiology/*therapy ; Permeability ; Probiotics/*therapeutic use ; }, abstract = {Obesity associated with low-grade chronic inflammation and intestinal dysbiosis is considered as a worldwide public health crisis. In the meanwhile, different probiotics have demonstrated beneficial effects on this condition, thus increasing the interest in the development of probiotic treatments. In this context, the aim of this study is to investigate the anti-obesity effects of potential probiotic Lactobacillus acidophilus isolated from the porcine gut. Then, it is found that L. acidophilus reduces body weight, fat mass, inflammation and insulin resistance in mice fed with a high-fat diet (HFD), accompanied by activation in brown adipose tissue (BAT) as well as improvements of energy, glucose and lipid metabolism. Besides, our data indicate that L. acidophilus not only reverses HFD-induced gut dysbiosis, as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin bearing Gram-negative bacteria levels, but also maintains intestinal barrier integrity, reduces metabolic endotoxemia, and inhibits the TLR4 / NF- κB signaling pathway. In addition, the results of microbiome phenotype prediction by BugBase and bacterial functional potential prediction using PICRUSt show that L. acidophilus treatment improves the gut microbiota functions involving metabolism, immune response, and pathopoiesia. Furthermore, the anti-obesity effect is transmissible via horizontal faeces transfer from L. acidophilus-treated mice to HFD-fed mice. According to our data, it is seen that L. acidophilus could be a good candidate for probiotic of ameliorating obesity and associated diseases such as hyperlipidemia, nonalcoholic fatty liver diseases, and insulin resistance through its anti-inflammatory properties and alleviation of endothelial dysfunction and gut dysbiosis.}, }
@article {pmid35384688, year = {2022}, author = {Cruz, N and Abernathy, GA and Dichosa, AEK and Kumar, A}, title = {The Age of Next-Generation Therapeutic-Microbe Discovery: Exploiting Microbe-Microbe and Host-Microbe Interactions for Disease Prevention.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0058921}, doi = {10.1128/iai.00589-21}, pmid = {35384688}, issn = {1098-5522}, abstract = {Humans are considered "superorganisms," harboring a diverse microbial collective that outnumbers human cells 10 to 1. Complex and gravely understudied host- and microbe-microbe interactions-the product of millions of years of host-microbe coevolution-govern the superorganism in almost every aspect of life functions and overall well-being. Abruptly disrupting these interactions via extrinsic factors has undesirable consequences for the host. On the other hand, supplementing commensal or beneficial microbes may mitigate perturbed interactions or enhance the interactive relationships that ultimately benefit all parties. Hence, immense efforts have focused on dissecting the innumerable host- and microbe-microbe relationships to characterize if a "positive" or "negative" interaction is at play and to exploit such behavior for broader implications. For example, microbiome research has worked to identify and isolate naturally antipathogenic microbes that may offer therapeutic potential either in a direct, one-on-one application or by leveraging its unique metabolic properties. However, the discovery and isolation of such desired therapeutic microbes from complex microbiota have proven challenging. Currently, there is no conventional technique to universally and functionally screen for these microbes. With this said, we first describe in this review the historical (probiotics) and current (fecal microbiota or defined consortia) perspectives on therapeutic microbes, present the discoveries of therapeutic microbes through exploiting microbe-microbe and host-microbe interactions, and detail our team's efforts in discovering therapeutic microbes via our novel microbiome screening platform. We conclude this minireview by briefly discussing challenges and possible solutions with therapeutic microbes' applications and paths ahead for discovery.}, }
@article {pmid35384391, year = {2022}, author = {Bloom, PP and Donlan, J and Torres Soto, M and Daidone, M and Hohmann, E and Chung, RT}, title = {Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient.}, journal = {Hepatology communications}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep4.1950}, pmid = {35384391}, issn = {2471-254X}, support = {Clinical Research Award//American College of Gastroenterology/ ; }, abstract = {Early data suggest fecal microbiota transplant (FMT) may treat hepatic encephalopathy (HE). Optimal FMT donor and recipient characteristics are unknown. We assessed the safety and efficacy of FMT in patients with prior overt HE, comparing five FMT donors. We performed an open-label study of FMT capsules, administered 5 times over 3 weeks. Primary outcomes were change in psychometric HE score (PHES) and serious adverse events (SAEs). Serial stool samples underwent shallow shotgun metagenomic sequencing. Ten patients completed FMT administration and 6-month follow-up. Model for End-Stage Liver Disease (MELD) score did not change after FMT (14 versus 14, p = 0.51). Thirteen minor adverse events and three serious adverse events (two unrelated to FMT) were reported. One SAE was extended-spectrum beta-lactamase Escherichia coli bacteremia. The PHES improved after three doses of FMT (+2.1, p < 0.05), after five doses of FMT (+2.9, p = 0.007), and 4 weeks after the fifth dose of FMT (+3.1, p = 0.02). Mean change in the PHES ranged from -1 to +6 by donor. Two taxa were identified by random forest analysis and confirmed by linear regression to predict the PHES- Bifidobacterium adolescentis (adjusted R2 = 0.27) and B. angulatum (adjusted R2 = 0.25)-both short-chain fatty acid (SCFA) producers. Patients who responded to FMT had higher levels of Bifidobacterium as well as other known beneficial taxa at baseline and throughout the study. The FMT donor with poorest cognitive outcomes in recipients had the lowest fecal SCFA levels. Conclusion: FMT capsules improved cognition in HE, with an effect varying by donor and recipient factors (NCT03420482).}, }
@article {pmid35382170, year = {2022}, author = {Eriksen, LL and Baunwall, SMD and Eriksen, PL and Bak-Fredslund, KP and Nielsen, JE and Dahlerup, JF and Thomsen, KL and Vilstrup, H and Hvas, CL}, title = {Deep hyperammonemic hepatic encephalopathy precipitated by fecal microbiota transplantation for fulminant Clostridioides difficile infection.}, journal = {Gastroenterology report}, volume = {10}, number = {}, pages = {goab043}, doi = {10.1093/gastro/goab043}, pmid = {35382170}, issn = {2052-0034}, }
@article {pmid35382160, year = {2022}, author = {Burstiner, LS and Silver, J and Burstiner, LJ and Teymoorian, A and Pallav, K and Jones, D and Owings, A and Glover, S}, title = {Escherichia coli O157: H7 sepsis following fecal microbiota transplant in an IgA-deficient inflammatory bowel disease patient.}, journal = {Gastroenterology report}, volume = {10}, number = {}, pages = {goab041}, doi = {10.1093/gastro/goab041}, pmid = {35382160}, issn = {2052-0034}, }
@article {pmid35278334, year = {2022}, author = {Donoso, F and Cryan, JF and Olavarría-Ramírez, L and Nolan, YM and Clarke, G}, title = {Inflammation, Lifestyle Factors, and the Microbiome-Gut-Brain Axis: Relevance to Depression and Antidepressant Action.}, journal = {Clinical pharmacology and therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1002/cpt.2581}, pmid = {35278334}, issn = {1532-6535}, support = {SFI/FFP/6820//Science Foundation Ireland Investigator Award/ ; //Reta Lila Weston Trust Award/ ; }, abstract = {Depression is considered a major public health concern, where existing pharmacological treatments are not equally effective across all patients. The pathogenesis of depression involves the interaction of complex biological components, such as the immune system and the microbiota-gut-brain axis. Adjunctive lifestyle-oriented approaches for depression, including physical exercise and special diets are promising therapeutic options when combined with traditional antidepressants. However, the mechanisms of action of these strategies are incompletely understood. Accumulating evidence suggests that physical exercise and specific dietary regimens can modulate both the immune system and gut microbiota composition. Here, we review the current information about the strategies to alleviate depression and their crosstalk with both inflammatory mechanisms and the gut microbiome. We further discuss the role of the microbiota-gut-brain axis as a possible mediator for the adjunctive therapies for depression through inflammatory mechanisms. Finally, we review existing and future adjunctive strategies to manipulate the gut microbiota with potential use for depression, including physical exercise, dietary interventions, prebiotics/probiotics, and fecal microbiota transplantation.}, }
@article {pmid35151729, year = {2022}, author = {Hu, C and Sun, B and Liu, M and Yu, J and Zhou, X and Chen, L}, title = {Fecal transplantation from young zebrafish donors efficiently ameliorates the lipid metabolism disorder of aged recipients exposed to perfluorobutanesulfonate.}, journal = {The Science of the total environment}, volume = {823}, number = {}, pages = {153758}, doi = {10.1016/j.scitotenv.2022.153758}, pmid = {35151729}, issn = {1879-1026}, mesh = {Animals ; Fecal Microbiota Transplantation ; Female ; Fluorocarbons ; Lipid Metabolism ; *Lipid Metabolism Disorders ; *Probiotics/pharmacology ; Sulfonic Acids ; Zebrafish ; }, abstract = {Aging is a biological process that is accompanied by the gradual loss of physiological functions. Under the context of ubiquitous and persistent environmental pollution, the elderly will be more vulnerable to the detrimental effects of toxic pollutants than the young. With objectives to explore effective measures to ameliorate the double stress of aging and toxicants, the present study transplanted the feces from young zebrafish donors to aged recipients, which were concurrently exposed to perfluorobutanesulfonate (PFBS), an emerging environmental pollutant of international concern. After exposure, growth, hepatic structural organization, and lipid metabolism were examined. The results showed that, irrespective of PFBS toxicity, transplantation of young feces significantly enhanced the growth of the aged. In the livers of aged and PFBS-exposed zebrafish, vacuolization symptom was prevalently observed, while young fecal transplantation alleviated the structural defects in aged livers. In the gut of the elderly, digestive activity of lipids was promoted after the transplantation of young feces. The blood of the aged females accumulated significantly higher concentration of triglyceride (TG) than the young counterparts (2.6-fold), implying that the elderly were at high risk of cardiovascular diseases. PFBS treatment of the aged further increased blood TG levels by 2.0-fold relative to the aged control group, pointing to the aggravation of the health of the elderly by environmental pollution. However, it is intriguing that young fecal transplantation efficiently inhibited the metabolic toxicity of PFBS and restored the normal level of blood TG, which provided more evidence about the benefit of young fecal transplant to improve the health of the aged individuals. In the aged livers transplanted with young feces, mitochondrial β-oxidation of fatty acids was consistently activated. Overall, the present study verified the efficacy of young fecal transplantation to mitigate the metabolic disorders resulting from aging and an environmental pollutant.}, }
@article {pmid35379265, year = {2022}, author = {Wang, H and Zhang, M and Li, J and Liang, J and Yang, M and Xia, G and Ren, Y and Zhou, H and Wu, Q and He, Y and Yin, J}, title = {Gut microbiota is causally associated with poststroke cognitive impairment through lipopolysaccharide and butyrate.}, journal = {Journal of neuroinflammation}, volume = {19}, number = {1}, pages = {76}, pmid = {35379265}, issn = {1742-2094}, support = {NSFC81870936//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Poststroke cognitive impairment (PSCI) is prevalent in stroke patients. The etiology of PSCI remains largely unknown. We previously found that stroke induces gut microbiota dysbiosis which affects brain injury. Hereby, we aimed to investigate whether the gut microbiota contributes to the pathogenesis of PSCI.
METHODS: 83 stroke patients were recruited and their cognitive function were measured by Montreal Cognitive Assessment (MoCA) scores 3 months after stroke onset. The peripheral inflammatory factor levels and gut microbiota compositions of the patients were analyzed. Fecal microbiota transplantation from patients to stroke mice was performed to examine the causal relationship between the gut microbiota and PSCI. The cognitive function of mice was evaluated by Morris water maze test.
RESULTS: 34 and 49 stroke patients were classified as PSCI and non-PSCI, respectively. Compared with non-PSCI patients, PSCI patients showed significantly higher levels of gut Enterobacteriaceae, lipopolysaccharide (LPS) and peripheral inflammation markers. Consistently, stroke mice that received microbiota from PSCI patients (PSCI mice) presented a higher level of Enterobacteriaceae, intestinal Toll-like receptor-4 (TLR4) expression, circulating LPS, LPS-binding protein (LBP) and inflammatory cytokines, and a lower level of fecal butyrate, severer intestine destruction and cognitive impairment than mice that received microbiota from nPSCI patients (nPSCI mice). In addition, we observed exacerbations in blood-brain barrier (BBB) integrity, microglial activation, neuronal apoptosis in the CA1 region of the hippocampus, and Aβ deposition in the thalamus of PSCI mice in comparison with nPSCI mice. Intraperitoneal injection of LPS after stroke caused similar pathology to those seen in PSCI mice. Supplementation with sodium butyrate (NaB) via drinking water rescued these detrimental changes in PSCI mice.
CONCLUSIONS: Our data indicate a cause-effect relationship between gut microbiota and PSCI for the first time, which is likely mediated by inflammation-regulating metabolites including LPS and butyrate.}, }
@article {pmid34826617, year = {2022}, author = {Ghani, R and Mullish, BH and Davies, FJ and Marchesi, JR}, title = {How to adapt an intestinal microbiota transplantation programme to reduce the risk of invasive multidrug-resistant infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {4}, pages = {502-512}, doi = {10.1016/j.cmi.2021.11.006}, pmid = {34826617}, issn = {1469-0691}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; MR/T005254/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19 ; Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Vulnerable patients with intestinal colonization of multidrug-resistant organisms (MDROs) are recognized to be at increased risk of invasive MDRO-driven infection. Intestinal microbiota transplantation (IMT, also called faecal microbiota transplant) is the transfer of healthy screened donor stool to an affected recipient, and recent interest has focused on its impact on the reduction of invasive MDRO infection.
OBJECTIVES: To describe how to establish a clinical IMT pathway for patients at risk of MDRO invasive infection, with special considerations for optimizing administration and assessment of endpoints.
SOURCES: Expert guidelines and peer-reviewed clinical studies are encompassed and discussed.
CONTENT: IMT is offered to patients with MDROs detected on rectal or stool screening and either at risk of MDRO invasive infection due to altered immune status or those with recurrent MDRO-mediated invasive disease and considered at risk of further disease. Donor screening should include pathogens with theoretical or demonstrated risk of transmission (including MDROs themselves and SARS-CoV-2) and take into consideration the relative immunosuppressed state of potential recipients. Delivery of IMT is timed for when the patient is free from active infection, but no additional antibiotics are indicated. If administered when future immunosuppression is to take place, IMT is aligned at least 2 weeks beforehand to ensure sufficient time for engraftment. Patients are followed up in terms of adverse effects from IMT and clinicians are advised to discuss with the IMT multidisciplinary team on choice of antibiotics if needed to take into consideration the impact upon the intestinal microbiome. Prevention of invasive disease is the primary measure of success, rather than using intestinal decolonization as a binary outcome. Repeat IMT is considered case by case.
IMPLICATIONS: Future research areas should include randomized studies that consider clinical outcomes and cost-effectiveness, and better understanding of mechanisms to identify markers of treatment success and functional microbiome components that could be used therapeutically.}, }
@article {pmid35372517, year = {2022}, author = {Baquero, F and Del Campo, R and Martínez, JL}, title = {Interventions in Nicotinamide Adenine Dinucleotide Metabolism, the Intestinal Microbiota and Microcin Peptide Antimicrobials.}, journal = {Frontiers in molecular biosciences}, volume = {9}, number = {}, pages = {861603}, doi = {10.3389/fmolb.2022.861603}, pmid = {35372517}, issn = {2296-889X}, abstract = {A proper NADH/NAD + balance allows for the flow of metabolic and catabolic activities determining cellular growth. In Escherichia coli, more than 80 NAD + dependent enzymes are involved in all major metabolic pathways, including the post-transcriptional build-up of thiazole and oxazole rings from small linear peptides, which is a critical step for the antibiotic activity of some microcins. In recent years, NAD metabolism boosting drugs have been explored, mostly precursors of NAD + synthesis in human cells, with beneficial effects on the aging process and in preventing oncological and neurological diseases. These compounds also enhance NAD + metabolism in the human microbiota, which contributes to these beneficial effects. On the other hand, inhibition of NAD + metabolism has been proposed as a therapeutic approach to reduce the growth and propagation of tumor cells and mitigating inflammatory bowel diseases; in this case, the activity of the microbiota might mitigate therapeutic efficacy. Antibiotics, which reduce the effect of microbiota, should synergize with NAD + metabolism inhibitors, but these drugs might increase the proportion of antibiotic persistent populations. Conversely, antibiotics might have a stronger killing effect on bacteria with active NAD + production and reduce the cooperation of NAD + producing bacteria with tumoral cells. The use of NADH/NAD + modulators should take into consideration the use of antibiotics and the population structure of the microbiota.}, }
@article {pmid35372103, year = {2022}, author = {Halaweish, HF and Boatman, S and Staley, C}, title = {Encapsulated Fecal Microbiota Transplantation: Development, Efficacy, and Clinical Application.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {826114}, doi = {10.3389/fcimb.2022.826114}, pmid = {35372103}, issn = {2235-2988}, abstract = {Fecal microbiota transplantation (FMT) has been established as a highly restorative therapeutic approach for treating recurrent Clostridioides difficile infection (rCDI). Recently, the use of capsule-based fecal microbiota transplantation (cFMT) has been shown to be a clinically effective approach to restore intestinal microbiota composition. This convenient, oral delivery provides an easy route of administration and a newfound flexibility for clinicians and patients. In this review, we discuss the development of cFMT, paying particular attention to lyophilized cFMT products. We review the available published clinical studies comparing cFMT with lower endoscopic FMT (eFMT) or placebo. We further discuss the pharmacokinetics of FMT, which should be understood in a framework of microbial ecology that considers the complex and dynamic interactions of gut microbiota with host factors and other microorganisms. Promisingly, the results of multiple trials investigating cFMT vs. eFMT in rCDI show cFMT to be as effective as eFMT at preventing rCDI. However, its efficacy in non-rCDI conditions, including obesity and metabolic syndrome, inflammatory bowel disease, HIV, and neurologic conditions, is less clear and more research is needed in these areas. Standardization of formulation, dose, and timing of administration to ensure optimal microbiota engraftment and clinical response is also a challenge to be addressed. Overall, cFMT is a practical method for fecal microbiota transplantation, with similar efficacy to eFMT in the resolution of rCDI, that holds therapeutic potential in a variety of other diseases.}, }
@article {pmid35371048, year = {2022}, author = {Brevi, A and Cogrossi, LL and Lorenzoni, M and Mattorre, B and Bellone, M}, title = {The Insider: Impact of the Gut Microbiota on Cancer Immunity and Response to Therapies in Multiple Myeloma.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {845422}, doi = {10.3389/fimmu.2022.845422}, pmid = {35371048}, issn = {1664-3224}, abstract = {The human microbiota is a unique set of microorganisms colonizing the human body and evolving within it from the very beginning. Acting as an insider, the microbiota provides nutrients, and mutualistically interacts with the host's immune system, thus contributing to the generation of barriers against pathogens. While a strong link has been documented between intestinal dysbiosis (i.e., disruption to the microbiota homeostasis) and diseases, the mechanisms by which commensal bacteria impact a wide spectrum of mucosal and extramucosal human disorders have only partially been deciphered. This is particularly puzzling for multiple myeloma (MM), a treatable but incurable neoplasia of plasma cells that accumulate in the bone marrow and lead to end-organ damage. Here we revise the most recent literature on data from both the bench and the bedside that show how the gut microbiota modulates cancer immunity, potentially impacting the progression of asymptomatic monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM) to full blown MM. We also explore the effect of the gut microbiome on hematopoietic stem cell transplantation, chemotherapy, immunomodulating therapy and cancer immunotherapy in MM patients. Additionally, we identify the most cogent area of investigation that have the highest chance to delineate microbiota-related and pathobiology-based parameters for patient risk stratification. Lastly, we highlight microbiota-modulating strategies (i.e., diet, prebiotics, probiotics, fecal microbiota transplantation and postbiotics) that may reduce treatment-related toxicity in patients affected by MM as well as the rates of undertreatment of SMM patients.}, }
@article {pmid35370847, year = {2022}, author = {Huang, HL and Xu, HM and Liu, YD and Shou, DW and Chen, HT and Nie, YQ and Li, YQ and Zhou, YJ}, title = {First Application of Fecal Microbiota Transplantation in Adult Asperger Syndrome With Digestive Symptoms-A Case Report.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {695481}, doi = {10.3389/fpsyt.2022.695481}, pmid = {35370847}, issn = {1664-0640}, abstract = {Asperger syndrome (AS) is a chronic neurodevelopmental disorder. Although all of the clinically diagnosed cases display normal intelligence and speech functions, barriers in social interaction and communication seriously affect mental health and psychological function. In addition to traditional psychological/behavioral training and symptomatic medication, in-depth studies of intestinal microbiota and mental health have indicated that probiotics (e.g., Lactobacillus rhamnosus) can effectively reduce the occurrence of AS. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient's gastrointestinal tract to improve the gut microenvironment. In this case report, we describe the first case of adult AS treated with FMT. The patient suffered from diarrhea-predominant irritable bowel syndrome for 6 years with symptoms of diarrhea and abdominal pain. After three rounds of FMT, the diarrhea and abdominal pain were significantly improved. Moreover, the symptoms of AS were also significantly ameliorated. We found that FMT changed the structure of the intestinal microbiota as well as the patient's serum metabolites, and these changes were consistent with the patient's symptoms. The metabolites may affect signaling pathways, as revealed by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The changes in microbial metabolites following FMT may affect other regions (e.g., the nervous system) via the circulatory system, such that the bacteria-gut-blood-brain axis may be the means through which FMT mitigates AS.}, }
@article {pmid35370631, year = {2022}, author = {Huang, Y and Xin, W and Xiong, J and Yao, M and Zhang, B and Zhao, J}, title = {The Intestinal Microbiota and Metabolites in the Gut-Kidney-Heart Axis of Chronic Kidney Disease.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {837500}, doi = {10.3389/fphar.2022.837500}, pmid = {35370631}, issn = {1663-9812}, abstract = {Emerging evidences demonstrate the involvement of gut microbiota in the progression of chronic kidney disease (CKD) and CKD-associated complications including cardiovascular disease (CVD) and intestinal dysfunction. In this review, we discuss the interactions between the gut, kidney and heart in CKD state, and elucidate the significant role of intestinal microbiota in the gut-kidney-heart axis hypothesis for the pathophysiological mechanisms of these diseases, during which process mitochondria may serve as a potential therapeutic target. Dysregulation of this axis will lead to a vicious circle, contributing to CKD progression. Recent studies suggest novel therapies targeting gut microbiota in the gut-kidney-heart axis, including dietary intervention, probiotics, prebiotics, genetically engineered bacteria, fecal microbiota transplantation, bacterial metabolites modulation, antibiotics, conventional drugs and traditional Chinese medicine. Further, the identification of specific microbial communities and their corresponding pathophysiological metabolites and the illumination of the gut-kidney-heart axis may contribute to innovative basic research, clinical trials and therapeutic strategies against CKD progression and uremic complications in CKD patients.}, }
@article {pmid35081663, year = {2022}, author = {Shehata, E and Parker, A and Suzuki, T and Swann, JR and Suez, J and Kroon, PA and Day-Walsh, P}, title = {Microbiomes in physiology: insights into 21st-century global medical challenges.}, journal = {Experimental physiology}, volume = {107}, number = {4}, pages = {257-264}, doi = {10.1113/EP090226}, pmid = {35081663}, issn = {1469-445X}, support = {//Newton-Mosharafa Scholarship Fund from the Egyptian Ministry of Higher Education (Cultural Affairs and Mission sector), the British Council and the British Embassy in Egypt/ ; //National Institute for Health Research (Leicester Biomedical Research Centre)/ ; //Medical Research Council (MRC) UK Consortium on MetAbolic Phenotyping (MAP/UK)/ ; BB/R012512/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10343/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10346/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10347/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10355/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {NEW FINDINGS: What is the topic of this review? The role of the gut microbiome in physiology and how it can be targeted as an effective strategy against two of the most important global medical challenges of our time, namely, metabolic diseases and antibacterial resistance. What advances does it highlight? The critical roles of the microbiome in regulating host physiology and how microbiome analysis is useful for disease stratification to enable informed clinical decisions and develop interventions such as faecal microbiota transplantation, prebiotics and probiotics. Also, the limitations of microbiome modulation, including the potential for probiotics to enhance antimicrobial resistance gene reservoirs, and that currently a 'healthy microbiome' that can be used as a biobank for transplantation is yet to be defined.
ABSTRACT: The human gut microbiome is a key factor in the development of metabolic diseases and antimicrobial resistance, which are among the greatest global medical challenges of the 21st century. A recent symposium aimed to highlight state-of-the-art evidence for the role of the gut microbiome in physiology, from childhood to adulthood, and the impact this has on global disease outcomes, ageing and antimicrobial resistance. Although the gut microbiome is established early in life, over time the microbiome and its components including metabolites can become perturbed due to changes such as dietary habits, use of antibiotics and age. As gut microbial metabolites, including short-chain fatty acids, secondary bile acids and trimethylamine-N-oxide, can interact with host receptors including G protein-coupled receptors and can alter host metabolic fluxes, they can significantly affect physiological homoeostasis leading to metabolic diseases. These metabolites can be used to stratify disease phenotypes such as irritable bowel syndrome and adverse events after heart failure and allow informed decisions on clinical management and treatment. While strategies such as use of probiotics, prebiotics and faecal microbiota transplantation have been proposed as interventions to treat and prevent metabolic diseases and antimicrobial resistance, caution must be exercised, first due to the potential of probiotics to enhance antimicrobial resistance gene reservoirs, and second, a 'healthy gut microbiome' that can be used as a biobank for transplantation is yet to be defined. We highlight that sampling other parts of the gastrointestinal tract may produce more representative data than the faecal microbiome alone.}, }
@article {pmid35365713, year = {2022}, author = {Smith, BJ and Piceno, Y and Zydek, M and Zhang, B and Syriani, LA and Terdiman, JP and Kassam, Z and Ma, A and Lynch, SV and Pollard, KS and El-Nachef, N}, title = {Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {5517}, pmid = {35365713}, issn = {2045-2322}, support = {1563159//National Science Foundation (NSF)/ ; 5T32DK007007//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; 5T32DK007007//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; 1563159//National Science Foundation (NSF)/ ; }, abstract = {Fecal microbiota transplant is a promising therapy for ulcerative colitis. Parameters maximizing effectiveness and tolerability are not yet clear, and it is not known how import the transmission of donor microbes to patients is. Here (clinicaltrails.gov: NCT03006809) we have tested the effects of antibiotic pretreatment and compared two modes of maintenance dose delivery, capsules versus enema, in a randomized, pilot, open-label, 2 × 2 factorial design with 22 patients analyzed with mild to moderate UC. Clinically, the treatment was well-tolerated with favorable safety profile. Of patients who received antibiotic pretreatment, 6 of 11 experienced remission after 6 weeks of treatment, versus 2 of 11 non-pretreated patients (log odds ratio: 1.69, 95% confidence interval: -0.25 to 3.62). No significant differences were found between maintenance dosing via capsules versus enema. In exploratory analyses, microbiome turnover at both the species and strain levels was extensive and significantly more pronounced in the pretreated patients. Associations were also revealed between taxonomic turnover and changes in the composition of primary and secondary bile acids. Together these findings suggest that antibiotic pretreatment contributes to microbiome engraftment and possibly clinical effectiveness, and validate longitudinal strain tracking as a powerful way to monitor the dynamics and impact of microbiota transfer.}, }
@article {pmid35357354, year = {2022}, author = {Kim, SY and Shin, J and Park, JS and Cha, B and Seo, Y and Park, SH and Lee, JH and Kim, JS and Kwon, G}, title = {The first report on effect of fecal microbiota transplantation as a complementary treatment in a patient with steroid-refractory Cronkhite-Canada syndrome: A case report.}, journal = {Medicine}, volume = {101}, number = {12}, pages = {e29135}, doi = {10.1097/MD.0000000000029135}, pmid = {35357354}, issn = {1536-5964}, abstract = {RATIONALE: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease of unknown etiology that is characterized by the appearance of multiple polyps in the entire gastrointestinal (GI) tract, except in the esophagus, with GI and non-GI symptoms. Various factors are associated with the pathogenesis of CCS. Immune dysregulation has been discussed as one of the pathogeneses of CCS, and dysbiosis of the gut microbiota can affect the immune system. Currently, standard treatment has not been established.
We present the treatment with fecal microbiota transplantation (FMT) in a 67-year-old male patient with steroid-refractory CCS who could not undergo anti-tumor necrosis factor-a treatment due to suspected tuberculosis infection.
INTERVENTIONS: FMT has recently attracted attention as a method of overcoming drug resistance through immunomodulatory effects through microbiome regulation. We collected the patient's stool samples before FMT and 8weeks after FMT.
OUTCOMES: We analyzed the microbiome composition of patients by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). After FMT, the number of episodes of diarrhea and hypoalbuminemia were also corrected. The Chao 1 index after FMT, which was significantly higher than that of donors before FMT, changed to a similar level for donors after FMT. Fusobacterium nucleatum, Pyramidobacter piscolens, and Campylobacter concisus disappeared after FMT, suggesting the presence of an association between gut microbiota and CCS.
LESSONS: Furthermore, we provide the possibility that microbiome modulation by FMT could serve as a complementary treatment in patients with steroid-refractory CCS.}, }
@article {pmid35355860, year = {2022}, author = {Gao, T and Wang, Z and Cao, J and Dong, Y and Chen, Y}, title = {The Role of Aeromonas-Goblet Cell Interactions in Melatonin-Mediated Improvements in Sleep Deprivation-Induced Colitis.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {8133310}, doi = {10.1155/2022/8133310}, pmid = {35355860}, issn = {1942-0994}, abstract = {Background: Our previous studies demonstrated that melatonin could effectively ameliorate sleep deprivation- (SD-) caused oxidative stress-mediated gut microbiota disorder and colitis. The research further clarified the mechanism of melatonin in improving colitis from the perspective of the interaction between Aeromonas and goblet cells.
Methods: A seventy-two hours SD mouse model with or without melatonin intervention and fecal microbiota transplantation (FMT) to explore the vital position of Aeromonas-goblet cell interactions in melatonin improving SD-induced colitis. Moreover, Aeromonas or LPS-supplied mice were assessed, and the influence of melatonin on Aeromonas-goblet cell interactions-mediated oxidative stress caused colitis. Furthermore, in vitro experiment investigated the regulation mechanism of melatonin.
Results: Our study showed that SD induced colitis, with upregulation of Aeromonas and LPS levels and reductions in goblet cells number and MUC2 protein. Similarly, FMT from SD mice, Aeromonas veronii colonization, and LPS treatment restored the SD-like goblet cells number and MUC2 protein decrease and colitis. Moreover, LPS treatment downregulated the colonic antioxidant capacity. Yet, melatonin intervention reversed all consequence in SD, A.veronii colonization, and LPS-treated mice. In vitro, melatonin reversed A. veronii- or LPS-induced MUC2 depletion in mucus-secreting human HT-29 cells via increasing the expression level of Villin, Tff3, p-GSK-3β, β-catenin, and melatonin receptor 2 (MT2) and decreasing the level of p-IκB, p-P65, ROS, TLR4, and MyD88 proteins, while the improvement effect was blocked with pretreatment with a MT2 antagonist but were mimicked by TLR4 and GSK-3β antagonists and ROS scavengers.
Conclusions: Our results demonstrated that melatonin-mediated MT2 inhibits Aeromonas-goblet cell interactions to restore the level of MUC2 production via LPS/TLR4/MyD88/GSK-3β/ROS/NF-κB loop, further improving colitis in SD mice.}, }
@article {pmid35298520, year = {2022}, author = {Groenewegen, B and van Lingen, E and Ooijevaar, RE and Wessels, E and Feltkamp, MCW and Boeije-Koppenol, E and Verspaget, HW and Kuijper, EJ and van Prehn, J and Keller, JJ and Terveer, EM and , }, title = {How to prepare stool banks for an appropriate response to the ongoing COVID-19 pandemic: Experiences in the Netherlands and a retrospective comparative cohort study for faecal microbiota transplantation.}, journal = {PloS one}, volume = {17}, number = {3}, pages = {e0265426}, pmid = {35298520}, issn = {1932-6203}, mesh = {Aged ; COVID-19/epidemiology/*prevention & control/transmission ; Clostridium Infections/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*virology ; Female ; Humans ; Male ; Netherlands/epidemiology ; Retrospective Studies ; SARS-CoV-2 ; *Tissue Banks ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an efficacious treatment for patients with recurrent Clostridioides difficile infections (rCDI). Stool banks facilitate FMT by providing screened faecal suspensions from highly selected healthy donors. Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic and the potential risk of SARS coronavirus-2 (SARS-CoV-2) transmission via FMT, many stool banks were forced to temporarily halt and adjust donor activities.
GOAL: The evaluation of a strategy to effectively continue stool banking activities during the ongoing COVID-19 pandemic.
STUDY: To restart our stool banking activities after an initial halt, we implemented periodic SARS-CoV-2 screening in donor faeces and serum, and frequent donor assessment for COVID-19 related symptoms. FMT donor and recipient data obtained before (2016-2019) and during the COVID-19 pandemic (March 2020-August 2021) were compared to assess stool banking efficacy.
RESULTS: Two out of ten donors developed COVID-19. No differences during versus before the COVID-19 pandemic were observed in the number of approved faeces donations (14 vs 22/month, p = 0.06), FMT requests for rCDI (3.9 vs 4.3/month, p = 0.6); rCDI patients eligible for FMT (80.6% vs 73.3%, p = 0.2); rCDI cure rate (90.3% vs 89.2%, p = 0.9); CDI-free survival (p = 0.7); the number of non-rCDI patients treated with FMT (0.5/month vs 0.4/month), and the number of possibly FMT related adverse events (9.5% vs 7.8%, p = 0.7). Two FMTs for rCDI were delayed due to COVID-19.
CONCLUSIONS: There is a continued need for FMT treatment of rCDI during the COVID-19 pandemic. Appropriate donor screening and SARS-CoV-2 infection prevention measures can be implemented in existing protocols without increasing the burden for donors, and allow safe, effective and efficient FMT during the ongoing COVID-19 pandemic. Stool banks should evaluate their SARS-CoV-2 donor screening protocols for long-term sustainability and efficacy, and share their experiences to help the utilisation, standardisation and improvement of stool banks worldwide.}, }
@article {pmid34370175, year = {2021}, author = {Moustafa, SA and Mohamed, S and Dawood, A and Azar, J and Elmorsy, E and Rizk, NAM and Salama, M}, title = {Gut brain axis: an insight into microbiota role in Parkinson's disease.}, journal = {Metabolic brain disease}, volume = {36}, number = {7}, pages = {1545-1557}, pmid = {34370175}, issn = {1573-7365}, mesh = {Anti-Bacterial Agents/therapeutic use ; Brain-Gut Axis/*physiology ; Dysbiosis/complications ; Fatty Acids, Volatile/physiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Lipids/physiology ; Parkinson Disease/drug therapy/*etiology ; Probiotics/therapeutic use ; alpha-Synuclein/physiology ; }, abstract = {Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. It is characterized neuropathologically by the presence of alpha-synuclein containing Lewy Bodies in the substantia nigra of the brain with loss of dopaminergic neurons in the pars compacta of the substantia nigra. The presence of alpha-synuclein aggregates in the substantia nigra and the enteric nervous system (ENS) drew attention to the possibility of a correlation between the gut microbiota and Parkinson's disease. The gut-brain axis is a two-way communication system, which explains how through the vagus nerve, the gut microbiota can affect the central nervous system (CNS), including brain functions related to the ENS, as well as how CNS can alter various gut secretions and immune responses. As a result, this dysbiosis or alteration in gut microbiota can be an early sign of PD with reported changes in short chain fatty acids, bile acids, and lipids. This gave rise to the use of probiotics and faecal microbiota transplantation as alternative approaches to improve the symptoms of patients with PD. The aim of this review is to discuss investigations that have been done to explore the gastrointestinal involvement in Parkinson's disease, the effect of dysbiosis, and potential therapeutic strategies for PD.}, }
@article {pmid35352640, year = {2022}, author = {Bhatt, S and Kanoujia, J and Mohanalakshmi, S and Patil, CR and Gupta, G and Chellappan, DK and Dua, K}, title = {Role of Brain-Gut-Microbiota Axis in Depression: Emerging Therapeutic Avenues.}, journal = {CNS & neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/1871527321666220329140804}, pmid = {35352640}, issn = {1996-3181}, abstract = {The human gut microbiota plays a significant role in the pathophysiology of central nervous system related diseases. Recent studies suggest correlations between the altered gut microbiota and major depressive disorder (MDD). It is proposed that normalization of the gut microbiota alleviates MDD. The imbalance of brain-gut-microbiota axis also results in dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. This imbalance has a crucial role in the pathogenesis of depression. Treatment strategies with certain antibiotics lead to the depletion of useful microbes and thereby induce depression like effects in subjects. Microbiota is also involved in the synthesis of various neurotransmitters (NTs) like 5-hydroxy tryptamine (5-HT; serotonin), norepinephrine (NE) and dopamine (DA). In addition to NTs, the gut microbiota also has influence on brain derived neurotrophic factor (BDNF) levels. Recent research findings have exhibited that transfer of stress prone microbiota in mice is also responsible for depression and anxiety-like behaviour in animals. The use of probiotics, prebiotics, synbiotics and proper diet have shown the beneficial effects in the regulation of depression pathogenesis. Moreover, transplantation of fecal microbiota from depressed individuals to the normal subjects also induces depression like symptoms. With the precedence of limited therapeutic benefits from monoamine targeting drugs, the regulation of brain-gut microbiota is emerging as a new treatment modality for MDDs. In this review, we elaborate the significance of brain-gut-microbiota axis in the progression of MDD, particularly focusing on the modulation of the gut microbiota as a mode of treating MDD.}, }
@article {pmid35349076, year = {2022}, author = {Sharma, A and Roy, A and Premkumar, M and Verma, N and Duseja, A and Taneja, S and Grover, S and Chopra, M and Dhiman, RK}, title = {Fecal microbiota transplantation in alcohol-associated acute-on-chronic liver failure: an open-label clinical trial.}, journal = {Hepatology international}, volume = {}, number = {}, pages = {}, pmid = {35349076}, issn = {1936-0541}, abstract = {BACKGROUND: Severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Alteration of gut microbiota is a crucial component implicated in its pathogenesis, whose modulation has been suggested as a potential therapeutic tool. We evaluated the safety of fecal microbiota transplantation (FMT) and its efficacy in improving short-term survival and clinical severity scores in patients with SAH-ACLF.
METHODS: Thirty-three patients [13 in the FMT arm; 20 in the standard of care arm (SOC)] with SAH-ACLF were included in this open-label study. A single FMT session was administered as a freshly prepared stool suspension from pre-identified healthy family member stool donors through a nasojejunal tube. Patients were followed up on days 7, 28, and 90.
RESULTS: Survival at 28 and 90 days was significantly better in the FMT arm (100% versus 60%, p = 0.01; 53.84% versus 25%, p = 0.02). Hepatic encephalopathy resolved in 100% versus 57.14% (FMT versus SOC, p = 0.11) patients, while ascites resolved in 100% versus 40% survivors (p = 0.04). Major adverse event rates, including spontaneous bacterial peritonitis and gastrointestinal bleeding, were similar in both groups (p = 0.77; p = 0.70). Median IL1beta decreased by 21.39% (IQR - 73.67 to 7.63) in the FMT group, whereas it increased in the SOC by 27.44% (IQR - 0.88 to 128.11) (p = 0.01). Percentage changes in bilirubin and ALT between baseline and day 7 emerged as predictors of 90-day mortality.
CONCLUSION: FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH-ACLF.
CLINICAL TRIAL NUMBER: NCT03827772 available from http://clinicaltrials.gov/ct2/show/NCT03827772 CTRI Reference number: CTRI/2019/02/017538 dated 7 February 2019.}, }
@article {pmid35347532, year = {2022}, author = {Fang, Z and Chen, M and Qian, J and Wang, C and Zhang, J}, title = {The Bridge Between Ischemic Stroke and Gut Microbes: Short-Chain Fatty Acids.}, journal = {Cellular and molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {35347532}, issn = {1573-6830}, abstract = {Short-chain fatty acids (SCFAs) are monocarboxylates produced by the gut microbiota (GM) and result from the interaction between diet and GM. An increasing number of studies about the microbiota-gut-brain axis (MGBA) indicated that SCFAs may be a crucial mediator in the MGBA, but their roles have not been fully clarified. In addition, there are few studies directly exploring the role of SCFAs as a potential regulator of microbial targeted interventions in ischemic stroke, especially for clinical studies. This review summarizes the recent studies concerning the relationship between ischemic stroke and GM and outlines the role of SCFAs as a bridge between them. The potential mechanisms by which SCFAs affect ischemic stroke are described. Finally, the beneficial effects of SFCAs-mediated therapeutic measures such as diet, dietary supplements (e.g., probiotics and prebiotics), fecal microbiota transplantation, and drugs on ischemic brain injury are also discussed.}, }
@article {pmid35346845, year = {2022}, author = {Chen, J and Wang, M and Zhang, P and Li, H and Qu, K and Xu, R and Guo, N and Zhu, H}, title = {Cordycepin alleviated metabolic inflammation in Western diet-fed mice by targeting intestinal barrier integrity and intestinal flora.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106191}, doi = {10.1016/j.phrs.2022.106191}, pmid = {35346845}, issn = {1096-1186}, abstract = {Metabolic inflammation is a crucial factor in the pathogenesis of obesity and promotes related complications. Accumulating evidence has indicated that regulating intestinal integrity and the gut microbiota may be new treatment strategies for metabolic inflammation and obesity. Cordycepin has been reported to improve obesity, but the mechanism is not yet clear. Here, we showed that cordycepin considerably alleviated systemic inflammation while reducing body weight gain and metabolic disorders in Western diet (WD)-fed mice. Further investigations showed that cordycepin significantly ameliorated WD-induced damage to the intestinal barrier and decreased the leakage of lipopolysaccharide (LPS) into the blood in mice by suppressing intestinal inflammation, oxidative stress damage, and decreasing intestinal epithelial cell apoptosis and pyroptosis. In addition, by using metagenomic sequencing, we found that cordycepin can also regulate the homeostasis of intestinal flora, including selectively increasing the abundance of Akkermansia muciniphila and reducing the production of fecal LPS. Besides, we demonstrated that the intestinal flora partially mediated the beneficial effects of cordycepin on improving intestinal barrier function, and obesity-related symptoms in WD-fed mice by a fecal microbiota transplantation experiment. Hence, our findings provided new insights into the role of cordycepin in improving metabolic inflammation and obesity from the perspective of regulating the intestinal barrier function and intestinal flora, and further provided data support for the utility of cordycepin in the treatment of obesity and its complications.}, }
@article {pmid35346337, year = {2022}, author = {Newsome, RC and Gharaibeh, RZ and Pierce, CM and da Silva, WV and Paul, S and Hogue, SR and Yu, Q and Antonia, S and Conejo-Garcia, JR and Robinson, LA and Jobin, C}, title = {Interaction of bacterial genera associated with therapeutic response to immune checkpoint PD-1 blockade in a United States cohort.}, journal = {Genome medicine}, volume = {14}, number = {1}, pages = {35}, pmid = {35346337}, issn = {1756-994X}, abstract = {BACKGROUND: Recent studies show that human gut microbial composition can determine whether a patient is a responder or non-responder to immunotherapy but have not identified a common microbial signal shared by responding patients. The functional relationship between immunity, intestinal microbiota, and NSCLC response to immune checkpoint inhibitor/inhibition (ICI) in an American cohort remains unexplored.
METHODS: RNAlater-preserved fecal samples were collected from 65 pre-treatment (baseline) and post-treatment stage III/IV NSCLC patients undergoing ICI therapy, categorized as responders or non-responders according to RECIST criteria. Pooled and individual responder and non-responder microbiota were transplanted into a gnotobiotic mouse model of lung cancer and treated with ICIs. 16S rDNA and RNA sequencing was performed on patient fecal samples, 16S rDNA sequencing on mouse fecal samples, and flow cytometric analysis on mouse tumor tissue.
RESULTS: Responder patients have both a different microbial community structure than non-responders (P = 0.004) and a different bacterial transcriptome (PC2 = 0.03) at baseline. Taxa significantly enriched in responders include amplicon sequence variants (ASVs) belonging to the genera Ruminococcus, Akkermansia, and Faecalibacterium. Pooled and individual responder microbiota transplantation into gnotobiotic mice decreased tumor growth compared to non-responder colonized mice following ICI (P = 0.023, P = 0.019, P = 0.008, respectively). Responder tumors showed an increased anti-tumor cellular phenotype following ICI treatment. Responder mice are enriched with ASVs belonging to the genera Bacteroides, Blautia, Akkermansia, and Faecalibacterium. Overlapping taxa mapping between human and mouse cohorts correlated with tumor size and weight revealed a network highlighting responder-associated ASVs belonging to the genera Colidextribacter, Frisingicoccus, Marvinbryantia, and Blautia which have not yet been reported.
CONCLUSIONS: The role of isolate-specific function and bacterial gene expression in gut microbial-driven responsiveness to ICI has been underappreciated. This work supports further investigation using isolate-driven models to characterize the mechanisms underlying this phenomenon.}, }
@article {pmid35345829, year = {2022}, author = {Zhang, F and Zhou, Y and Chen, H and Jiang, H and Zhou, F and Lv, B and Xu, M}, title = {Curcumin Alleviates DSS-Induced Anxiety-Like Behaviors via the Microbial-Brain-Gut Axis.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {6244757}, doi = {10.1155/2022/6244757}, pmid = {35345829}, issn = {1942-0994}, abstract = {The anxiety and depression caused by inflammatory bowel diseases (IBD) are known to greatly affect the mental health of patients. The mechanism of psychiatric disorders caused by IBD is not fully understood. Previous research has suggested that the gut microbiome plays a key role in IBD. Curcumin is a yellow polyphenol extracted from the rhizome of the ginger plant, which has been shown to have effects against both depression and anxiety. Research has indicated that curcumin affects the gut microbiome and exerts antianxiety and neuroprotective effects through the microbiota-gut-brain axis (MGB). However, whether curcumin can alleviate the psychiatric disorders caused by IBD and how curcumin affects the MGB axis through the gut microbiota have not been fully understood. Therefore, this study was aimed at determining the metabolic parameters and microbiological environment in the peripheral and central nervous system to determine the effects of curcumin against anxiety induced by dextran sulfate sodium salt (DSS) in mice. To elaborate on the link between the gut microbiota and how curcumin alleviates anxiety-like behaviors, we performed a fecal microbiota transplantation (FMT) experiment. The results suggested that curcumin can effectively relieve anxiety-like behaviors caused by DSS in mice. Further, curcumin treatment can alleviate disturbances in the gut microbiota and systemic disorders of lipid metabolism caused by DSS. Finally, through FMT, we verified that curcumin increased phosphatidylcholine in the prefrontal cortex of the mice and alleviated DSS-induced anxiety-like behaviors by modulating specific gut microbiota. We also revealed that Muribaculaceae may be a key part of the gut microbiota for curcumin to alleviate DSS-induced anxiety-like behaviors through the MGB axis.}, }
@article {pmid35345443, year = {2022}, author = {Fan, Y and Su, Q and Chen, J and Wang, Y and He, S}, title = {Gut Microbiome Alterations Affect Glioma Development and Foxp3 Expression in Tumor Microenvironment in Mice.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {836953}, doi = {10.3389/fonc.2022.836953}, pmid = {35345443}, issn = {2234-943X}, abstract = {Glioma is the most common malignant tumor of the central nervous system (CNS), with high degree of malignancy and poor prognosis. The gut microbiome (GM) is composed of microorganisms with different properties and functions, which play an important role in human physiology and biological activities. It has been proved that GM can affect the development of glioma through natural immunity, but whether GM can affect glioma through adaptive immunity and whether there are some microorganisms in the GM that may affect glioma growth still remain unclear. In our study, we evaluated the relationship between GM and glioma. We proved that (I) glioma growth can induce structural changes of mouse GM, including the decreased abundance of Bacteroidia and increased abundance of Firmicutes. (II) GM dysbiosis can downregulate Foxp3 expression in the brain and promote glioma growth. A balanced environment of GM can upregulate the expression of Foxp3 in the brain and delay the development of glioma. (III) The increased abundance of Bacteroidia is associated with accelerated glioma progression, while its decreased abundance is associated with delayed glioma progression, which may be one of the key microorganisms affecting glioma growth. This study is helpful to reveal the relationship between GM and glioma development and provide new ideas for adjuvant therapy of glioma.}, }
@article {pmid35344215, year = {2022}, author = {Noye Tuplin, EW and Alukic, E and Lowry, DE and Chleilat, F and Wang, W and Cho, NA and Sampsell, K and Sales, KM and Mayengbam, S and McCoy, KD and Reimer, RA}, title = {Dietary fiber combinations to mitigate the metabolic, microbial, and cognitive imbalances resulting from diet-induced obesity in rats.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {36}, number = {5}, pages = {e22269}, doi = {10.1096/fj.202101750R}, pmid = {35344215}, issn = {1530-6860}, support = {//Snyder Institute for Chronic Diseases/ ; //Alberta Innovates | Alberta Innovates - Health Solutions (AIHS)/ ; //U of C | Alberta Children's Hospital Research Institute (ACHRI)/ ; //Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; //Faculty of Kinesiology Dean's Doctoral Scholarship/ ; //University of Calgary Eyes High Postdoctoral Fellowship/ ; }, abstract = {Dietary fiber promotes a healthy gut microbiome and shows promise in attenuating the unfavorable microbial changes resulting from a high-fat/sucrose (HFS) diet. High-fiber diets consisting of oligofructose alone (HFS/O) or in combination with β-glucan (HFS/OB), resistant starch (HFS/OR), or β-glucan and resistant starch (HFS/OBR) were fed to diet-induced obese rats for 8 weeks to determine if these fibers could attenuate the obese phenotype. Only the HFS/O group displayed a decrease in body weight and body fat, but all fiber interventions improved insulin sensitivity and cognitive function. The HFS/O diet was the least effective at improving cognitive function and only the HFS/OB group showed improvements in glucose tolerance, thus highlighting the differential effects of fiber types. Hippocampal cytokines (IL-6, IL-10) were more pronounced in the HFS/OB group which coincided with the most time spend in the open arms of the elevated plus maze. All fiber groups showed an increase in beneficial Bifidobacterium and Lactobacillus abundance while the HFS group showed higher abundance of Clostridium. Fecal microbiota transplant from fiber-treated rats into germ-free mice did not alter body composition in the mice but did result in a higher abundance of Bacteroides in the HFS/O and HFS/OB groups compared to HFS. The HFS/OB recipient mice also had higher insulin sensitivity compared to the other groups. This study highlights the influence of dietary fiber type on metabolic and cognitive outcomes suggesting that the type of supplementation (single or combined fibers) could be tailored to specific targeted outcomes.}, }
@article {pmid35340247, year = {2022}, author = {Feng, H and He, L and Wang, Z and Pi, B and Liu, Z}, title = {Phillygenin Protects the Intestinal Barrier from Dysfunction via let-7b Signaling Pathway and Regulation of Intestinal Microbiota.}, journal = {Journal of healthcare engineering}, volume = {2022}, number = {}, pages = {4769709}, doi = {10.1155/2022/4769709}, pmid = {35340247}, issn = {2040-2309}, abstract = {The study investigates the positive effects of phillygenin on intestinal tight junction via the let-7b signaling pathway and the regulation of intestinal microbiota. The expression levels of tight junction proteins are determined through PCR and Western blot. DSS-induced mice colitis is used to verify the protective effects of phillygenin on intestinal barrier and tight junction. Fecal microbiota transplantation is used to verify the role intestinal microbiota. let-7b is detected in the colon tissues of patients with acute stercoral obstruction. Phillygenin could promote the expression of occludin, which might be inhibited by let-7b inhibitor. DSS-induced mice colitis showed that phillygenin could lower the colonic permeability and maintain the tight junction-associated proteins. The effects of phillygenin could be deprived by anti-let-7b and rescued by FMT of normal intestinal microbiota. Clinical samples verified a lower level of let-7b in stercoral obstruction patients. Phillygenin could protect the intestinal barrier from dysfunction via the signaling pathway of let-7b by regulating intestinal microbiota.}, }
@article {pmid35339829, year = {2022}, author = {Yang, J and Zhang, Z and Xie, Z and Bai, L and Xiong, P and Chen, F and Zhu, T and Peng, Q and Wu, H and Zhou, Y and Ma, Y and Zhang, Y and Chen, M and Gao, J and Tian, W and Shi, K and Du, Y and Duan, Y and Wang, H and Xu, Y and Kuang, YQ and Zhu, M and Yu, J and Wang, K}, title = {Metformin modulates microbiota-derived inosine and ameliorates methamphetamine-induced anxiety and depression-like withdrawal symptoms in mice.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {149}, number = {}, pages = {112837}, doi = {10.1016/j.biopha.2022.112837}, pmid = {35339829}, issn = {1950-6007}, abstract = {BACKGROUND: Metformin exhibits therapeutic potential in behavioural deficits induced by methamphetamine (METH) in rats. Emerging studies suggest gut microbiota may impact psychiatric symptoms, but there is no direct evidence supporting metformin's participation in the pathophysiology of withdrawal symptoms via modulation of gut microbiota.
METHODS: In order to define the functional impacts of gut microbiota and metformin to the behavioural deficits during METH withdrawal, we utilized a combination of fecal microbiota transplantation (FMT), high-throughput sequencing, and untargeted metabolomics technologies.
RESULTS: First, METH addicts exhibited higher α diversity and distinct microbial structures compared to healthy controls. In particular, the relative abundance of Rikenellaceae was positively correlated with the severity of anxiety and depression. Second, both human-to-mouse and mouse-to-mouse FMTs confirmed that METH-altered-microbiota transplantation is sufficient to promote anxiety and depression-like behaviours in recipient germ-free mice, and these behavioural disturbances could be ameliorated by metformin. In-depth analysis revealed that METH significantly altered the bacterial composition and structure as well as relative abundance of several bacterial taxa and metabolites, including Rikenellaceae and inosine, respectively, whereas add-on metformin could remodel these alterations. Finally, the inosine complementation successfully restored METH-induced anxiety and depression-like behaviours in mice.
CONCLUSION: This study demonstrates that METH withdrawal-induced anxiety and depression-like behaviours are reversible and transmissible via gut microbiota in a mouse model. The therapeutic effects of metformin on psychiatric manifestations are associated with microbiota-derived metabolites, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.}, }
@article {pmid35339730, year = {2022}, author = {Kattner, AA}, title = {About gladiators and a sacred disease.}, journal = {Biomedical journal}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bj.2022.03.006}, pmid = {35339730}, issn = {2320-2890}, abstract = {In this special edition of the Biomedical Journal the reader gains an insight into drug-resistant epilepsy and according treatment approaches involving deep brain stimulation, the ketogenic diet and fecal microbiota transplant. Another emphasis is put on personalized medicine strategies, and covered in articles about the use of natriuretic peptides against cancer, along with an article about companion diagnostics involving extracellular vesicles. Recurrent infection with C. difficile, associated risk factors and therapeutic options are discussed. We learn about a mechanism that helps Leishmania evade a host control mechanism, receive an update about human adenovirus and are presented with characteristic magnetic resonance neuroimaging in COVID-19 pediatric patients. An advanced assessment in pediatric septic shock and an improved model for a pediatric early warning system are proposed. Some of the genetic causes of renal hypomagnesemia are explored, the impact of air pollution on children is examined, and an antisiphon device is described for surgical treatment of hydrocephalus. The relation between energy metabolism, circadian rhythm and its influence on the ATPase in the SCN are investigated, and among others some of the genetics influencing smoking duration and lung cancer. Finally it is discussed how embryo quality can be improved in in vitro fertilization, and what impact high estradiol has on blastocyst implantation. The outcome of surgery to correct mandibular deficiency is assessed, and in two letters the inclusion of observational studies in the evaluation of clinical trials related to COVID-19 is elaborated.}, }
@article {pmid35337386, year = {2022}, author = {Podlesny, D and Arze, C and Dörner, E and Verma, S and Dutta, S and Walter, J and Fricke, WF}, title = {Metagenomic strain detection with SameStr: identification of a persisting core gut microbiota transferable by fecal transplantation.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {53}, pmid = {35337386}, issn = {2049-2618}, support = {316130265//Deutsche Forschungsgemeinschaft/ ; 316130265//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: The understanding of how microbiomes assemble, function, and evolve requires metagenomic tools that can resolve microbiota compositions at the strain level. However, the identification and tracking of microbial strains in fecal metagenomes is challenging and available tools variably classify subspecies lineages, which affects their applicability to infer microbial persistence and transfer.
RESULTS: We introduce SameStr, a bioinformatic tool that identifies shared strains in metagenomes by determining single-nucleotide variants (SNV) in species-specific marker genes, which are compared based on a maximum variant profile similarity. We validated SameStr on mock strain populations, available human fecal metagenomes from healthy individuals and newly generated data from recurrent Clostridioides difficile infection (rCDI) patients treated with fecal microbiota transplantation (FMT). SameStr demonstrated enhanced sensitivity to detect shared dominant and subdominant strains in related samples (where strain persistence or transfer would be expected) when compared to other tools, while being robust against false-positive shared strain calls between unrelated samples (where neither strain persistence nor transfer would be expected). We applied SameStr to identify strains that are stably maintained in fecal microbiomes of healthy adults over time (strain persistence) and that successfully engraft in rCDI patients after FMT (strain engraftment). Taxonomy-dependent strain persistence and engraftment frequencies were positively correlated, indicating that a specific core microbiota of intestinal species is adapted to be competitive both in healthy microbiomes and during post-FMT microbiome assembly. We explored other use cases for strain-level microbiota profiling, as a metagenomics quality control measure and to identify individuals based on the persisting core gut microbiota.
CONCLUSION: SameStr provides for a robust identification of shared strains in metagenomic sequence data with sufficient specificity and sensitivity to examine strain persistence, transfer, and engraftment in human fecal microbiomes. Our findings identify a persisting healthy adult core gut microbiota, which should be further studied to shed light on microbiota contributions to chronic diseases. Video abstract.}, }
@article {pmid35333590, year = {2022}, author = {Puntillo, M and Segli, F and Champagne, CP and Raymond, Y and Vinderola, G}, title = {Functional Microbes and Their Incorporation into Foods and Food Supplements: Probiotics and Postbiotics.}, journal = {Annual review of food science and technology}, volume = {13}, number = {}, pages = {385-407}, doi = {10.1146/annurev-food-052720-011545}, pmid = {35333590}, issn = {1941-1421}, abstract = {Life expectancy has dramatically increased over the past 200 years, but modern life factors such as environmental exposure, antibiotic overuse, C-section deliveries, limited breast-feeding, and diets poor in fibers and microbes could be associated with the rise of noncommunicable diseases such as overweight, obesity, diabetes, food allergies, and colorectal cancer as well as other conditions such as mental disorders. Microbial interventions that range from transplanting a whole undefined microbial community from a healthy gut to an ill one, e.g., so-called fecal microbiota transplantation or vaginal seeding, to the administration of selected well-characterized microbes, either live (probiotics) or not (postbiotics), with efficacy demonstrated in clinical trials, may be effective tools to treat or prevent acute and chronic diseases that humans still face, enhancing the quality of life.}, }
@article {pmid35325852, year = {2022}, author = {Du, L and Li, Q and Yi, H and Kuang, T and Tang, Y and Fan, G}, title = {Gut microbiota-derived metabolites as key actors in type 2 diabetes mellitus.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {149}, number = {}, pages = {112839}, doi = {10.1016/j.biopha.2022.112839}, pmid = {35325852}, issn = {1950-6007}, abstract = {Type 2 diabetes mellitus (T2DM) is one of the most risk factors threatening human health. Although genetic and environmental factors contribute to the development of T2DM, gut microbiota has also been found to be involved. Gut microbiota-derived metabolites are a key factor in host-microbe crosstalk, and have been revealed to play a central role in the physiology and physiopathology of T2DM. In this review, we provide a timely and comprehensive summary of the microbial metabolites that are protective or causative for T2DM, including some amino acids-derived metabolites, short-chain fatty acids, trimethylamine N-oxide, and bile acids. The mechanisms by which metabolites affect T2DM have been elaborated. Knowing more about these processes will increase our understanding of the causal relationship between gut microbiota and T2DM. Moreover, some frontier therapies that target gut microbes and their metabolites to improve T2DM, including dietary intervention, fecal microbiota transplantation, probiotics, prebiotics or synbiotics intervention, and drugging microbial metabolism, have been critically discussed. This review may provide novel insights for the development of targeted and personalized treatments for T2DM based on gut microbial metabolites. More high-quality clinical trials are needed to accelerate the clinical translation of gut-targeted therapies for T2DM.}, }
@article {pmid35316318, year = {2022}, author = {Liu, Z and Yan, C and Lin, X and Ai, C and Dong, X and Shao, L and Wang, S and Song, S and Zhu, B}, title = {Responses of the gut microbiota and metabolite profiles to sulfated polysaccharides from sea cucumber in humanized microbiota mice.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d1fo04443e}, pmid = {35316318}, issn = {2042-650X}, abstract = {Sea cucumber Stichopus japonicus has been consumed as functional food traditionally in Asia, and its sulfated polysaccharide (SCSPsj) demonstrates health-promoting effects in rodents which are related to the regulation of the gut microbiota. However, little is known about the response of the human gut microbiota to SCSPsj. Therefore, the present study aimed to study the response of the donor microbiota to SCSPsj in vivo through a humanized microbiota mice model, which was constructed by antibiotic treatment combined with fecal microbiota transplant. The results revealed that the SCSPsj supplement could positively interact with the specific donor microbiota. It could significantly regulate the gut microbiota community, especially the abundance of Lactobacillus. In addition, SCSPsj could modulate the metabolites in serum and cecal contents of mice, including short-chain fatty acids (SCFAs) and lactic acid, and the changes of some bioactive metabolites were associated with the gut microbiota enriched by SCSPsj. Furthermore, in vitro experiments demonstrated that the Lactobacillus strains isolated could not be proliferated directly by SCSPsj, but SCSPsj significantly promoted biofilm formation and mucus binding of Lactobacillus spp., which contributed to the enrichment of Lactobacillus in vivo. The present study could provide insight into the application of SCSPsj as microbiota-directed food.}, }
@article {pmid35312296, year = {2022}, author = {Ju, Z and Shen, L and Zhou, M and Luo, J and Yu, Z and Qu, C and Lei, R and Lei, M and Huang, R}, title = {Helicobacter pylori and Alzheimer's Disease-Related Metabolic Dysfunction: Activation of TLR4/Myd88 Inflammation Pathway from p53 Perspective and a Case Study of Low-Dose Radiation Intervention.}, journal = {ACS chemical neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1021/acschemneuro.2c00082}, pmid = {35312296}, issn = {1948-7193}, abstract = {Gut dysbiosis is observed in Alzheimer's disease (AD) and is frequently associated with AD-induced metabolic dysfunction. However, the extent and specific underlying molecular mechanisms triggered by alterations of gut microbiota composition and function mediating AD-induced metabolic dysfunction in AD remain incompletely uncovered. Here, we indicate that Helicobacter pylori (H. pylori) is abundant in AD patients with relative metabolic dysfunction. Fecal microbiota transplantation from the AD patients promoted metabolic dysfunction in mice and increased gut permeability. H. pylori increased gut permeability through activation of the TLR4/Myd88 inflammation pathway in a p53-dependent manner, leading to metabolic dysfunction. Moreover, p53 deficiency reduced bile acid concentration, leading to an increased abundance of H. pylori colonization. Overall, these data identify H. pylori as a key promoter of AD-induced metabolic dysfunction.}, }
@article {pmid35312112, year = {2022}, author = {Wang, Y and Xu, Y and Xu, X and Wang, H and Wang, D and Yan, W and Zhu, J and Hao, H and Wang, G and Cao, L and Zhang, J}, title = {Ginkgo biloba extract ameliorates atherosclerosis via rebalancing gut flora and microbial metabolism.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.7439}, pmid = {35312112}, issn = {1099-1573}, support = {81720108032//National Natural Science Foundation of China/ ; 81773986//National Natural Science Foundation of China/ ; 81930109//National Natural Science Foundation of China/ ; 81973559//National Natural Science Foundation of China/ ; G20582017001//Overseas Expertise Introduction Project for Discipline Innovation/ ; SZSM201801060//Sanming Project of Medicine in Shenzhen/ ; SKLNMZZ202020//the Project of State Key Laboratory of Natural Medicines, China Pharmaceutical University/ ; }, abstract = {The Ginkgo biloba leave extract (GbE) is widely applied in the prevention and treatment of atherosclerotic cardiovascular diseases in clinical practice. However, its mechanism of actions has not been totally elucidated. In this study, we confirmed the beneficial effects of GbE in alleviating hypercholesterolemia, inflammation and atherosclerosis in Ldlr-/- mice, which were fed 12 weeks of Western diet (WD). Moreover, 16S rRNA sequencing revealed that GbE treatment reshaped the WD-perturbed intestinal microbiota, particularly decreased the Firmicutes/Bacteroidetes ratio and elevated the abundance of Akkermansia, Alloprevotella, Alistipes, and Parabacteroides. Furthermore, GbE treatment downregulated the intestinal transcriptional levels of proinflammatory cytokines and enhanced the expression of tight junction proteins, exerting the roles of attenuating the intestinal inflammation as well as repairing the gut barrier. Meanwhile, the targeted metabolomic analysis displayed that GbE treatment significantly reversed the dysfunction of the microbial metabolic phenotypes, including promoting the production of short chain fatty acids, indole-3-acetate and secondary bile acids, which were correlated with the atherosclerotic plaque areas. Finally, we confirmed GbE-altered gut microbiota was sufficient to alleviate atherosclerosis by fecal microbiota transplantation. In summary, our findings provide important insights into the pharmacological mechanism underlying the antiatherogenic efficacy of GbE.}, }
@article {pmid35310733, year = {2022}, author = {Tominaga, K and Tsuchiya, A and Mizusawa, T and Matsumoto, A and Minemura, A and Oka, K and Takahashi, M and Yoshida, T and Kojima, Y and Ogawa, K and Kawata, Y and Nakajima, N and Kimura, N and Abe, H and Setsu, T and Takahashi, K and Sato, H and Ikarashi, S and Hayashi, K and Mizuno, KI and Yokoyama, J and Tajima, Y and Nakano, M and Shimada, Y and Kameyama, H and Wakai, T and Terai, S}, title = {Utility of autologous fecal microbiota transplantation and elucidation of microbiota in diversion colitis.}, journal = {DEN open}, volume = {2}, number = {1}, pages = {e63}, pmid = {35310733}, issn = {2692-4609}, abstract = {Objectives: Diversion colitis (DC) is an inflammatory disorder caused by interruption of the fecal stream and subsequent nutrient deficiency from luminal bacteria. The utility of fecal microbiota transplantation (FMT) for DC was recently investigated; however, the precise pathogenesis of this condition remains unclear. This study aimed to evaluate the utility of autologous FMT in DC and to determine the related changes in the intestinal microbiota.
Methods: Autologous FMT was performed to reestablish the intestinal microbiota in five patients (average age, 64.6 ± 8.3 years) with DC. They underwent double-ended colostomy. We assessed the diverted colon by endoscopy and evaluated the microbiota before and after FMT using the 16S rRNA gene sequencing method.
Results: All five patients had mild inflammation (ulcerative colitis endoscopic index of severity [UCEIS] 2-3) in the diverted colon based on the colonoscopic findings. Three patients presented with symptoms, such as tenesmus, mucoid stool, and bloody stool. With FMT treatment, all patients achieved endoscopic remission (UCEIS score of 0 or 1) and symptomatic improvement. We observed a significantly decreased α-diversity in DC patients compared to healthy controls. The frequency of aerobic bacteria, such as Enterobacteriaceae, in the diverted colon decreased after autologous FMT.
Conclusions: This study was the first to show that the microbiota in the diverted colon was significantly affected by autologous FMT. Since interruption of the fecal stream is central to the development of DC, FMT can be considered a promising treatment.}, }
@article {pmid35309933, year = {2022}, author = {Liu, J and Gao, Z and Liu, C and Liu, T and Gao, J and Cai, Y and Fan, X}, title = {Alteration of Gut Microbiota: New Strategy for Treating Autism Spectrum Disorder.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {792490}, pmid = {35309933}, issn = {2296-634X}, abstract = {Autism spectrum disorder (ASD) is defined as a complex heterogeneous disorder and characterized by stereotyped behavior and deficits in communication and social interactions. The emerging microbial knowledge has pointed to a potential link between gut microbiota dysbiosis and ASD. Evidence from animal and human studies showed that shifts in composition and activity of the gut microbiota may causally contribute to the etiopathogenesis of core symptoms in the ASD individuals with gastrointestinal tract disturbances and act on microbiota-gut-brain. In this review, we summarized the characterized gut bacterial composition of ASD and the involvement of gut microbiota and their metabolites in the onset and progression of ASD; the possible underlying mechanisms are also highlighted. Given this correlation, we also provide an overview of the microbial-based therapeutic interventions such as probiotics, antibiotics, fecal microbiota transplantation therapy, and dietary interventions and address their potential benefits on behavioral symptoms of ASD. The precise contribution of altering gut microbiome to treating core symptoms in the ASD needs to be further clarified. It seemed to open up promising avenues to develop microbial-based therapies in ASD.}, }
@article {pmid35308555, year = {2022}, author = {Cao, C and Zhu, H and Yao, Y and Zeng, R}, title = {Gut Dysbiosis and Kidney Diseases.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {829349}, pmid = {35308555}, issn = {2296-858X}, abstract = {Gut dysbiosis is defined as disorders of gut microbiota and loss of barrier integrity, which are ubiquitous on pathological conditions and associated with the development of various diseases. Kidney diseases are accompanied with gut dysbiosis and metabolic disorders, which in turn contribute to the pathogenesis and progression of kidney diseases. Microbial alterations trigger production of harmful metabolites such as uremic toxins and a decrease in the number of beneficial ones such as SCFAs, which is the major mechanism of gut dysbiosis on kidney diseases according to current studies. In addition, the activation of immune responses and mitochondrial dysfunction by gut dysbiosis, also lead to the development of kidney diseases. Based on the molecular mechanisms, modification of gut dysbiosis via probiotics, prebiotics and synbiotics is a potential approach to slow kidney disease progression. Fecal microbiota transplantation (FMT) and genetic manipulation of the gut microbiota are also promising choices. However, the clinical use of probiotics in kidney disease is not supported by the current clinical evidence. Further studies are necessary to explore the causal relationships of gut dysbiosis and kidney diseases, the efficiency and safety of therapeutic strategies targeting gut-kidney axis.}, }
@article {pmid35308525, year = {2022}, author = {Chen, L and Zhu, Y and Hou, X and Yang, L and Chu, H}, title = {The Role of Gut Bacteria and Fungi in Alcohol-Associated Liver Disease.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {840752}, pmid = {35308525}, issn = {2296-858X}, abstract = {Cirrhosis and liver cancer caused by alcohol-associated liver disease (ALD) are serious threats to people's health. In addition to hepatic cell apoptosis and liver inflammation caused by oxidative stress during alcohol metabolism, intestinal microbiota disorders are also involved in the onset and development of ALD. Ethanol and its' oxidative and non-oxidative metabolites, together with dysbiosis-caused-inflammation, destroys the intestinal barrier. Changes of several microbial metabolites, such as bile acids, short-chain fatty acids, and amino acid, are closely associated with gut dysbiosis in ALD. The alcohol-caused dysbiosis can further influence intestinal barrier-related proteins, such as mucin2, bile acid-related receptors, and aryl hydrocarbon receptor (AhR), and these abnormal changes also participate in the injury of the intestinal barrier and hepatic steatosis. Gut-derived bacteria, fungi, and their toxins, such as lipopolysaccharide (LPS) and β-glucan translocate into the liver through the damaged intestinal barrier and promote the progression of inflammation and fibrosis of ALD. Thus, the prevention of alcohol-induced disruption of intestinal permeability has a beneficial effect on ALD. Currently, multiple therapeutic treatments have been applied to restore the gut microbiota of patients with ALD. Fecal microbial transplantation, probiotics, antibiotics, and many other elements has already shown their ability of restoring the gut microbiota. Targeted approaches, such as using bacteriophages to remove cytolytic Enterococcus faecalis, and supplement with Lactobacillus, Bifidobacterium, or boulardii are also powerful therapeutic options for ALD.}, }
@article {pmid35307002, year = {2022}, author = {Singhal, S and Rani, V}, title = {Therapeutic Effects of Gut Microbiota on Metabolic Syndrome: A Patent Review.}, journal = {Recent patents on food, nutrition & agriculture}, volume = {}, number = {}, pages = {}, doi = {10.2174/2212798412666220318162322}, pmid = {35307002}, issn = {1876-1429}, abstract = {BACKGROUND: The balanced composition of the gut microbiota is essential for human health. The dysbiotic condition may develop various complex diseases. A metabolic syndrome is a group of biochemical and physiological abnormalities that can increase the risk of cardiovascular diseases, diabetes, and inflammatory diseases. It has become a serious concern worldwide because there is no acceptable medication to overcome this problem.
OBJECTIVE: This review aims to evaluate the relationship between gut microbiota and metabolic syndrome. Balance of gut microbiota relates to human health as well as diseases. Patents-related to significant findings on probiotics, prebiotics, synbiotics, and fecal microbiota transplantation signify the importance of the proposed theme and provide promising therapeutic strategies to modulate the dysbiotic condition and reoccurrence of beneficial microbial species during metabolic syndromes. Screening of patents-related databases can be worth full to track new technology. Therefore, some selected recent patents related to gut microbiota and associated therapies have been discussed in the present manuscript.
CONCLUSION: Under the existing situation, the role of gastrointestinal microbiota as a therapeutic agent is becoming more utilized for treating human health issues and various metabolic syndromes including obesity, diabetes, and cardiovascular diseases. Understanding gut dysbiosis and associated complex interactions between microbes and hosts would be effective for designing future therapeutic interventions for metabolic syndrome. Our detailed patent analysis reflects that gut dysbiosis has a prominent role in metabolic syndromes and dietary therapeutic strategies can improve health by modulating the human microbiota, their metabolites ad stability.}, }
@article {pmid35305720, year = {2022}, author = {Giles, J and Roberts, A}, title = {Clostridioides difficile: Current overview and future perspectives.}, journal = {Advances in protein chemistry and structural biology}, volume = {129}, number = {}, pages = {215-245}, doi = {10.1016/bs.apcsb.2021.11.003}, pmid = {35305720}, issn = {1876-1631}, abstract = {The most common world-wide cause of antibiotic-associated infectious diarrhea and colitis is the toxin producing bacterium, Clostridioides difficile (C. difficile). Here we review the background and characteristics of the bacterium and the toxins produced together with the epidemiology and the complex pathogenesis that leads to a broad clinical spectrum of disease. The review describes the difficulties faced in obtaining a quick and accurate diagnosis despite the range of sensitive and specific diagnostic tools available. We also discuss the problem of disease recurrence and the importance of disease prevention. The high rates of infection recurrence mean that treatment strategies are constantly under review and we outline the diverse treatment options that are currently in use and explore the emerging treatment options of pulsed antibiotic use, microbial replacement therapies and the use of monoclonal antibodies. We summarize the future direction of treatment strategies which include the development of novel antibiotics, the administration of oral polyclonal antibody formulations, the use of vaccines, the administration of competitive non-toxigenic spores and the neutralization of antibiotics at the microbiota level. Future successful treatments will likely involve a combination of therapies to provide the most effective and robust approach to C. difficile management.}, }
@article {pmid34902790, year = {2021}, author = {Yao, D and Dai, W and Dong, M and Dai, C and Wu, S}, title = {MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis.}, journal = {EBioMedicine}, volume = {74}, number = {}, pages = {103751}, doi = {10.1016/j.ebiom.2021.103751}, pmid = {34902790}, issn = {2352-3964}, mesh = {Anti-Bacterial Agents/therapeutic use ; Colitis, Ulcerative/*metabolism/microbiology/pathology/therapy ; Combined Modality Therapy ; Dietary Supplements ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/pathology ; Mucin-2/*metabolism ; }, abstract = {The mucin2 (MUC2) mucus barrier acts as the first barrier that prevents direct contact between intestinal bacteria and colonic epithelial cells. Bacterial factors related to the MUC2 mucus barrier play important roles in the response to changes in dietary patterns, MUC2 mucus barrier dysfunction, contact stimulation with colonic epithelial cells, and mucosal and submucosal inflammation during the occurrence and development of ulcerative colitis (UC). In this review, these underlying mechanisms are summarized and updated, and related interventions for treating UC, such as dietary adjustment, exogenous repair of the mucus barrier, microbiota transplantation and targeted elimination of pathogenic bacteria, are suggested. Such interventions are likely to induce and maintain a long and stable remission period and reduce or even avoid the recurrence of UC. A better mechanistic understanding of the MUC2 mucus barrier and its related bacterial factors may help researchers and clinicians to develop novel approaches for treating UC.}, }
@article {pmid34801681, year = {2022}, author = {Huang, S and Hu, S and Liu, S and Tang, B and Liu, Y and Tang, L and Lei, Y and Zhong, L and Yang, S and He, S}, title = {Lithium carbonate alleviates colon inflammation through modulating gut microbiota and Treg cells in a GPR43-dependent manner.}, journal = {Pharmacological research}, volume = {175}, number = {}, pages = {105992}, doi = {10.1016/j.phrs.2021.105992}, pmid = {34801681}, issn = {1096-1186}, mesh = {Adult ; Aged ; Animals ; Anti-Inflammatory Agents/pharmacology/*therapeutic use ; Colitis/chemically induced/*drug therapy/immunology/microbiology ; Dextran Sulfate ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Humans ; Lithium Carbonate/pharmacology/*therapeutic use ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Receptors, G-Protein-Coupled/*genetics ; T-Lymphocytes, Regulatory/*drug effects/immunology ; }, abstract = {BACKGROUND: Recent evidence suggests that neuropsychiatric stabilizers have a place in resolving gastrointestinal disorders. Lithium carbonate (LC) is one of the most commonly used drugs for bipolar disorder clinically. Here, we estimate the therapeutic function of LC against colitis and investigate the mechanism of intestinal flora and metabolism modulation.
METHODS: A colitis model was constructed by continuously administering 2.5% dextran sodium sulfate (DSS) solution daily for 7 days. Analysis of gut microbiota was carried out by 16S rRNA gene high-throughput sequencing. Spectrum antibiotic cocktail (ABX) and faecal microbiota transplantation (FMT) were employed to evaluate the protective effect of intestinal flora. Colonic Treg cells and related immune responses were detected by flow cytometry.
RESULTS: LC treatment significantly alleviated colon inflammation by regulating gut microbial diversity and altering flora composition. Notably, LC treatment upregulated short-chain fatty acid (SCFA)-producing bacteria, especially Akkermansia muciniphila (A. muciniphila), and transformed metabolite SCFA profiles. LC activated anti-inflammatory Treg cell responses in colonic lamina propria (LP) in a G-protein coupled receptor 43 (GPR43)-dependent mechanism. ABX, FMT and single bacteria gavage experiments were conducted to confirm the above mechanism.
CONCLUSIONS: As an intestinal microbiome and metabolite modulator, LC alleviates colon inflammation in a GPR43-dependent manner through activating Treg cell responses. Therefore, the therapeutic strategy of the microbiome-metabolite-immune axis, as observed in the A. muciniphila-SCFA-Treg cell axis in our study, might provide a new direction for the treatment of IBD.}, }
@article {pmid34555295, year = {2022}, author = {Shan, Y and Lee, M and Chang, EB}, title = {The Gut Microbiome and Inflammatory Bowel Diseases.}, journal = {Annual review of medicine}, volume = {73}, number = {}, pages = {455-468}, doi = {10.1146/annurev-med-042320-021020}, pmid = {34555295}, issn = {1545-326X}, support = {RC2 DK122394/DK/NIDDK NIH HHS/United States ; R01 DK113788/DK/NIDDK NIH HHS/United States ; }, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases ; *Microbiota ; }, abstract = {Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports a bidirectional relationship between disease progression and changes in microbiota membership and function. Thus, the study of the gut microbiome and host-microbe interactions should provide critical insights into disease pathogenesis as well as leads for developing microbiome-based diagnostics and interventions for IBD. In this article, we review the most recent advances in understanding the relationship between the gut microbiota and IBD and highlight the importance of going beyond establishing description and association to gain mechanistic insights into causes and consequences of IBD. The review aims to contextualize recent findings to form conceptional frameworks for understanding the etiopathogenesis of IBD and for the future development of microbiome-based diagnostics and interventions.}, }
@article {pmid34189475, year = {2021}, author = {Choo, JM and Rogers, GB}, title = {Gut microbiota transplantation for colonization of germ-free mice.}, journal = {STAR protocols}, volume = {2}, number = {3}, pages = {100610}, pmid = {34189475}, issn = {2666-1667}, mesh = {Anaerobiosis ; Animals ; Bioreactors ; *Fecal Microbiota Transplantation ; Germ-Free Life ; Mice ; }, abstract = {The use of germ-free mice is integral to the understanding of host-gut microbiome relationships. Such models rely on faithful replication of the donor microbiome to establish causal effects of the gut microbiota on host pathophysiology. This protocol describes the preparation and transfer of donor microbiota, focusing on strict anaerobic processing methods and multiple instillations by gavage for optimal gut microbiota recovery. For complete details on the generation and use of this protocol, please refer to Choo and Rogers (2021).}, }
@article {pmid35303781, year = {2022}, author = {Wei, Y and Peng, S and Lian, C and Kang, Q and Chen, J}, title = {Anorexia nervosa and gut microbiome: implications for weight change and novel treatments.}, journal = {Expert review of gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1080/17474124.2022.2056017}, pmid = {35303781}, issn = {1747-4132}, abstract = {INTRODUCTION: Host-microbiota interactions may be involved in many physical and psychological functions ranging from the digestion of food, maintenance of immune homeostasis, to the regulation of mood and cognition. Microbiome dysbiosis has been consistently described in many diseases. The pathogenesis and weight regulation mechanism in anorexia nervosa (AN) also seem to be implicated in the dynamic bidirectional adjustment of the microbiota-gut-brain axis. This review aims at elucidating this relationship.
AREA COVERED: This review starts with a description of pathogenic gut-brain pathways. Next we focus on the latest research on the associations between gut microbiota and weight change in the condition of AN. The strategies to alter the intestinal microbiome for the treatment of this disorder are discussed, including dietary, probiotics, prebiotics, synbiotics and fecal microbiota transplantation.
EXPERT OPINION: Gut microbiome is inextricably linked to AN. It may regulate weight gain in the process of refeeding via the microbiota-gut-brain axis, while the specific mechanism has yet to be clearly established. In the future, a better understanding of gut microbiome could have implications for developing microbiome-based prevention, diagnostics and therapies.}, }
@article {pmid35234303, year = {2022}, author = {Majewska-Szczepanik, M and Kowalczyk, P and Marcińska, K and Strzępa, A and Lis, GJ and Wong, FS and Szczepanik, M and Wen, L}, title = {Obesity aggravates contact hypersensitivity reaction in mice.}, journal = {Contact dermatitis}, volume = {}, number = {}, pages = {}, doi = {10.1111/cod.14088}, pmid = {35234303}, issn = {1600-0536}, support = {DK045735//Foundation for the National Institutes of Health/ ; IP2012 0443 72//Ministry of Science and Higher Education/ ; K/ZDS/007123//Ministry of Science and Higher Education/ ; }, abstract = {BACKGROUND: Obesity is associated with chronic, low-grade inflammation in tissues and predisposes to various complications, including inflammatory skin diseases. However, the link between obesity and contact hypersensitivity (CHS) is not fully understood.
OBJECTIVES: We sought to determine the influence of obesity on T helper 1 (Th1)-mediated CHS.
METHODS: The activity/phenotype/cytokine profile of the immune cells was tested in vivo and in vitro. Using quantitative polymerase chain reaction (qPCR) and fecal microbiota transplantation (FMT), we tested the role of a high-fat diet (HFD)-induced gut microbiota (GM) dysbiosis in increasing the effects of CHS.
RESULTS: Exacerbated CHS correlates with an increased inflammation-inducing GM in obese mice. We showed a proinflammatory milieu in the subcutaneous adipose tissue of obese mice, accompanied by proinflammatory CD4+ T cells and dendritic cells in skin draining lymph nodes and spleen. Obese interleukin (IL)-17A-/-B6 mice are protected from CHS aggravation, suggesting the importance of IL-17A in CHS aggravation in obesity.
CONCLUSIONS: Obesity creates a milieu that induces more potent CHS-effector cells but does not have effects on already activated CHS-effector cells. IL-17A is essential for the pathogenesis of enhanced CHS during obesity. Our study provides novel knowledge about antigen-specific responses in obesity, which may help with the improvement of existing treatment and/or in designing novel treatment for obesity-associated skin disorders.}, }
@article {pmid35302268, year = {2022}, author = {El-Salhy, M and Mazzawi, T and Hausken, T and Hatlebakk, JG}, title = {Irritable bowel syndrome patients who are not likely to respond to fecal microbiota transplantation.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e14353}, doi = {10.1111/nmo.14353}, pmid = {35302268}, issn = {1365-2982}, support = {40145//Helse Fonna/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) interventions have recently been advocated to not succeed in every irritable bowel syndrome (IBS) patient, since the outcome of FMT varies with the IBS subset. This study investigated the factors potentially affecting FMT response using the same patient cohort used in our previous study.
METHODS: This study included 109 patients who received allogenic FMT. Patients completed five questionnaires that assessed their symptoms and quality of life at baseline and at 2 weeks, 1 month, and 3 months after FMT. Patients also provided fecal samples at baseline and 1 month after FMT. The fecal bacterial profile and dysbiosis index (DI) were determined using 16S rRNA gene PCR DNA amplification covering variable genes V3-V9. Response to FMT was defined as a decrease of ≥50 points in the total IBS-SSS score after FMT.
RESULTS: An IBS patient's response or nonresponse to FMT was not determined by age, IBS duration, IBS subtype, IBS symptoms, fatigue, quality of life, or DI. There were more male nonresponders than responders, and the fluorescence signals of Alistipes were lower in nonresponders than in responders.
CONCLUSIONS: We concluded that IBS patients who are male and/or have low fecal Alistipes levels are most likely to not respond to FMT treatment. Whether low fecal Alistipes levels could be used as a marker for predicting the outcome of FMT remains to be determined. www.
CLINICALTRIALS: gov (NCT03822299).}, }
@article {pmid35301705, year = {2022}, author = {Pan, Z and Hu, Y and Huang, Z and Han, N and Li, Y and Zhuang, X and Yin, J and Peng, H and Gao, Q and Zhang, W and Huang, Y and Cui, Y and Bi, Y and Xu, ZZ and Yang, R}, title = {Alterations in gut microbiota and metabolites associated with altitude-induced cardiac hypertrophy in rats during hypobaric hypoxia challenge.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {35301705}, issn = {1869-1889}, abstract = {The gut microbiota is involved in host responses to high altitude. However, the dynamics of intestinal microecology and their association with altitude-related illness are poorly understood. Here, we used a rat model of hypobaric hypoxia challenge to mimic plateau exposure and monitored the gut microbiome, short-chain fatty acids (SCFAs), and bile acids (BAs) over 28 d. We identified weight loss, polycythemia, and pathological cardiac hypertrophy in hypoxic rats, accompanied by a large compositional shift in the gut microbiota, which is mainly driven by the bacterial families of Prevotellaceae, Porphyromonadaceae, and Streptococcaceae. The aberrant gut microbiota was characterized by increased abundance of the Parabacteroides, Alistipes, and Lactococcus genera and a larger Bacteroides to Prevotella ratio. Trans-omics analyses showed that the gut microbiome was significantly correlated with the metabolic abnormalities of SCFAs and BAs in feces, suggesting an interaction network remodeling of the microbiome-metabolome after the hypobaric hypoxia challenge. Interestingly, the transplantation of fecal microbiota significantly increased the diversity of the gut microbiota, partially inhibited the increased abundance of the Bacteroides and Alistipes genera, restored the decrease of plasma propionate, and moderately ameliorated cardiac hypertrophy in hypoxic rats. Our results provide an insight into the longitudinal changes in intestinal microecology during the hypobaric hypoxia challenge. Abnormalities in the gut microbiota and microbial metabolites contribute to the development of high-altitude heart disease in rats.}, }
@article {pmid35300220, year = {2022}, author = {Hu, C and Patil, Y and Gong, D and Yu, T and Li, J and Wu, L and Liu, X and Yu, Z and Ma, X and Yong, Y and Chen, J and Gooneratne, R and Ju, X}, title = {Heat Stress-Induced Dysbiosis of Porcine Colon Microbiota Plays a Role in Intestinal Damage: A Fecal Microbiota Profile.}, journal = {Frontiers in veterinary science}, volume = {9}, number = {}, pages = {686902}, doi = {10.3389/fvets.2022.686902}, pmid = {35300220}, issn = {2297-1769}, abstract = {The pathological mechanisms of gastrointestinal disorders, including inflammatory bowel disease (IBD), in pigs are poorly understood. We report the induction of intestinal inflammation in heat-stressed (HS) pigs, fecal microbiota transplantation from pigs to mice, and explain the role of microorganisms in IBD. 24 adult pigs were subjected to HS (34 ± 1 °C; 75-85% relative humidity for 24h) while 24 control pigs (CP) were kept at 25 ± 3°C and the same humidity. Pigs were sacrificed on days 1, 7, 14, 21. Colonic content microbiome analyses were conducted. Pseudo-germ-free mice were fed by gavage with fecal microbiota from HS-pigs and CP to induce pig-like responses in mice. From 7 d, HS-pigs exhibited fever and diarrhea, and significantly lower colonic mucosal thickness, crypt depth/width, and goblet cell number. Compared with each control group, the concentration of cortisol in the peripheral blood of HS pigs gradually increased, significantly so on days 7, 14, and 21 (P < 0.01). While the concentration of LPS in HS pigs' peripheral blood was significantly higher on days 7, 14 (P < 0.01), and 21 (P < 0.05) compared with that of the control group. The colonic microbiome composition of HS-pigs was different to that of CP. By day 14, opportunistic pathogens (e.g., Campylobacterales) had increased in HS-pigs. The composition of the colonic microbiome in mice administered feces from HS-pigs was different from those receiving CP feces. Bacteroides were significantly diminished, Akkermansia were significantly increased, and intestinal damage and goblet cell numbers were higher in mice that received HS-pig feces. Moreover, we verified the relevance of differences in the microbiota of the colon among treatments. Heat stress promotes changes in gut microbiome composition, which can affect the colonic microbial structure of mice through fecal microbiota transplantation; the molecular mechanisms require further investigation. This study enhanced our understanding of stress-induced inflammation in the colon and the increase in diarrhea in mammals subjected to prolonged HS. Our results provide useful information for preventing or ameliorating deficits in pig production caused by prolonged exposure to high temperatures.}, }
@article {pmid35299780, year = {2022}, author = {Liu, CK and Seo, J and Pravodelov, V and Frazier, S and Guy, M and Concilio, K and Lau-Ng, R and Brandeis, G and Watson, J and van der Velde, J and Olesen, SW and Budree, S and Njenga, M and Kassam, Z and Osman, M}, title = {Pilot study of autologous fecal microbiota transplants in nursing home residents: Feasibility and safety.}, journal = {Contemporary clinical trials communications}, volume = {27}, number = {}, pages = {100906}, doi = {10.1016/j.conctc.2022.100906}, pmid = {35299780}, issn = {2451-8654}, abstract = {Introduction: Antibiotic resistant bacterial infections (ARBIs) are extremely common in nursing home residents. These infections typically occur after a course of antibiotics, which eradicate both pathological and beneficial organisms. The eradication of beneficial organisms likely facilitates subsequent ARBIs. Autologous fecal microbiota transplant (aFMT) has been proposed as a potential treatment to reduce ARBIs in nursing home residents. Our objective was to determine the feasibility and safety of aFMT in a nursing home population.
Methods: Pilot clinical trial. We evaluated feasibility as total number of stool samples collected for aFMT production and safety as the number and relatedness of serious (SAE) and non-serious adverse events (AE).
Results: We screened 468 nursing home residents aged ≥18 years for eligibility; 67 enrolled, distributed among three nursing homes. Participants were 62.7% female and 35.8% Black. Mean age was 82.2 ± 8.5 years. Thirty-three participants underwent successful stool collection. Seven participants received antibiotics; four participants underwent aFMT. There were 40 SAEs (17 deaths) and 11 AEs. In the aFMT group, there were 3 SAEs (2 deaths) and 10 AEs. All SAEs and AEs were judged unrelated to the study intervention.
Conclusions: In this pilot study of aFMT in nursing home residents, less than half were able to provide adequate stool samples for aFMT. There were no related SAEs or AEs during the study. In sum, we conclude aFMT has limited feasibility in a nursing home population due to logistic and technical challenges but is likely safe.
Trial registration: ClinicalTrials.gov Identifier: NCT03061097.}, }
@article {pmid35297473, year = {2022}, author = {Nivet, C and Duhalde, V and Beaurain, M and Delobel, P and Quelven, I and Alric, L}, title = {Fecal Microbiota Transplantation for Refractory Clostridioides Difficile Infection Is Effective and Well Tolerated Even in Very Old Subjects: A Real-Life Study.}, journal = {The journal of nutrition, health & aging}, volume = {26}, number = {3}, pages = {290-296}, doi = {10.1007/s12603-022-1756-1}, pmid = {35297473}, issn = {1760-4788}, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is an innovative therapy indicated for the treatment of recurrent Clostridioides difficile infections. Although CDI and its complications are more common in very old patients (≥80 years) due to their comorbidities, frailty and senescence of the immune system, limited data are available for this older patient population.
DESIGN: This was a single-center, real-life cohort study with retrospective outcome data registration, conducted at Toulouse, France.
SETTING AND PARTICIPANTS: Older people group was compared to the control group aged 18-79 years.
MEASUREMENTS: The primary outcome was overall survival at 52 weeks for ≥80 years patients compared to the control group after FMT. Recurrence-free survival at 52 weeks and, the occurrence of adverse events in the short and long term were the secondary endpoints.
RESULTS: A total of 58 patients were included, 19 were aged ≥80 years and 39 were aged 18-79 years. Overall survival at 52 weeks after FMT of the very old patients was not different from the control group (78.9% versus 89.7%, p= 0.29). Recurrence-free survival of CDI was not different between groups, with 94.3% in the 18-79-group versus 86.9% in the ≥80 group (p=0.44). The occurrence of short- or long-term adverse events was not statistically different between the two groups (36.8% vs 41%, p=0.45).
CONCLUSIONS: FMT is effective and well-tolerated in very old frail patients. This treatment brings a rapid benefit and limits the loss of functions. It also favors their maintenance at home or in a non-medical institution dedicated to dependent subjects and improves their quality of life.}, }
@article {pmid35297188, year = {2022}, author = {Ishibashi, R and Furusawa, Y and Honda, H and Watanabe, Y and Fujisaka, S and Nishikawa, M and Ikushiro, S and Kurihara, S and Tabuchi, Y and Tobe, K and Takatsu, K and Nagai, Y}, title = {Isoliquiritigenin attenuates adipose tissue inflammation and metabolic syndrome by modifying gut bacteria composition in mice.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2101119}, doi = {10.1002/mnfr.202101119}, pmid = {35297188}, issn = {1613-4133}, abstract = {SCOPE: Isoliquiritigenin (ILG) has been reported to attenuate adipose tissue inflammation and metabolic disorder; however, the underlying mechanisms remain to be elucidated. The aim of this study is to elucidate whether ILG shows the anti-inflammatory and antimetabolic syndrome effects through gut microbiota modification.
METHODS & RESULTS: Mice were fed a high-fat diet (HFD) with or without ILG for up to 12 weeks. The effect of ILG on body weight, blood glucose level, adipose tissue inflammation, gut barrier function, and gut microbiota composition were investigated. ILG supplementation alleviated HFD-induced obesity, glucose tolerance, and insulin resistance and suppressed inflammatory gene expression in epididymal white adipose tissue (eWAT). Moreover, ILG supplementation modified gut bacterial composition by increasing the abundance of antimetabolic disease-associated species (e.g., Parabacteroides goldsteinii and Akkemansia muciniphila) and up-regulated genes associated with gut barrier function. Fecal microbiome transplantation (FMT) from ILG-fed donors counteracted HFD-induced body and eWAT weight changes, inflammation-related gene expression, glucose tolerance, and insulin resistance, thereby suggesting that ILG-responsive gut bacteria exert anti-inflammatory and antimetabolic syndrome effects.
CONCLUSION: Alterations in gut bacteria underly the beneficial effects of ILG against adipose tissue inflammation and metabolic disorders. ILG may be a promising prebiotic for the prevention and treatment of metabolic syndrome . This article is protected by copyright. All rights reserved.}, }
@article {pmid35295757, year = {2022}, author = {Wu, J and Lv, L and Wang, C}, title = {Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {827395}, doi = {10.3389/fcimb.2022.827395}, pmid = {35295757}, issn = {2235-2988}, abstract = {Background: Randomized controlled trials (RCTs) have examined the efficacy of fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) with inconsistent results. We performed a meta-analysis to assess both the short- and long-term efficacy of FMT in IBS.
Methods: MEDLINE, EMBASE, and the Cochrane Central Register were searched through September 2021. RCTs recruiting adult patients with IBS that compared FMT with placebo with dichotomous data of response to therapy were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of symptom not improving after therapy. RR was also pooled for adverse events (AEs). Continuous data were calculated using a mean difference for IBS-Quality of Life (IBS-QoL). GRADE methodology was used to assess quality of evidence.
Results: The search strategy generated 658 citations. Seven RCTs comprising 472 patients with IBS were included. FMT was not associated with a significant improvement in global symptom in IBS at 12 weeks in comparison with placebo (RR 0.75, 95% CI 0.43-1.31) with high heterogeneity between studies (I2 87%). Subgroup analyses showed that FMT was superior to placebo when administered via colonoscopy or gastroscope (RR 0.70, 95% CI 0.51-0.96; RR 0.37, 95% CI 0.14-0.99, respectively, while FMT was inferior to placebo when administered via oral capsules (RR 1.88, 95% CI 1.06-3.35). FMT induced a significant improvement in IBS-QoL compared to placebo (mean difference 9.39, 95% CI 3.86-14.91) at 12 weeks. No significant difference in the total number of AEs was observed between FMT and placebo (RR 1.20, 95% CI 0.59-2.47). FMT did not significantly improve global symptom in IBS at 1-year follow-up compared with placebo (RR 0.90, 95% CI 0.72-1.12). The GRADE quality evidence to support recommending FMT in IBS was very low.
Conclusion: IBS patients may benefit from FMT when administered via colonoscopy or gastroscope. FMT may improve the quality of life of IBS. The long-term use of FMT in IBS warrants further investigation. There is very-low-quality evidence to support recommending FMT in IBS.}, }
@article {pmid35292746, year = {2022}, author = {Hosokawa, M and Endoh, T and Kamata, K and Arikawa, K and Nishikawa, Y and Kogawa, M and Saeki, T and Yoda, T and Takeyama, H}, title = {Strain-level profiling of viable microbial community by selective single-cell genome sequencing.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {4443}, pmid = {35292746}, issn = {2045-2322}, support = {21H01733//Japan Society for the Promotion of Science/ ; 17H06158//Japan Society for the Promotion of Science/ ; }, abstract = {Culture-independent analysis with high-throughput sequencing has been widely used to characterize bacterial communities. However, signals derived from non-viable bacteria and non-cell DNA may inhibit its characterization. Here, we present a method for viable bacteria-targeted single-cell genome sequencing, called PMA-SAG-gel, to obtain comprehensive whole-genome sequences of surviving uncultured bacteria from microbial communities. PMA-SAG-gel uses gel matrixes that enable sequential enzymatic reactions for cell lysis and genome amplification of viable single cells from the microbial communities. PMA-SAG-gel removed the single-amplified genomes (SAGs) derived from dead bacteria and enabled selective sequencing of viable bacteria in the model samples of Escherichia coli and Bacillus subtilis. Next, we demonstrated the recovery of near-complete SAGs of eight oxygen-tolerant bacteria, including Bacteroides spp. and Phocaeicola spp., from 1331 human feces SAGs. We found the presence of two different strains in each species and identified their specific genes to investigate the metabolic functions. The survival profile of an entire population at the strain level will provide the information for understanding the characteristics of the surviving bacteria under the specific environments or sample processing and insights for quality assessment of live bacterial products or fecal microbiota transplantation and for understanding the effect of antimicrobial treatments.}, }
@article {pmid35292630, year = {2022}, author = {Daniel, N and Nachbar, RT and Tran, TTT and Ouellette, A and Varin, TV and Cotillard, A and Quinquis, L and Gagné, A and St-Pierre, P and Trottier, J and Marcotte, B and Poirel, M and Saccareau, M and Dubois, MJ and Joubert, P and Barbier, O and Koutnikova, H and Marette, A}, title = {Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {1343}, pmid = {35292630}, issn = {2041-1723}, abstract = {Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota. We further show that yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters. These metabolites are generated upon milk fermentation and concentrated in yogurt. Remarkably, diet-induced obesity reduces plasma and tissue BCHA levels, and this is partly prevented by dietary yogurt intake. We further show that BCHA improve insulin action on glucose metabolism in liver and muscle cells, identifying BCHA as cell-autonomous metabolic regulators and potential mediators of yogurt's health effects.}, }
@article {pmid35291651, year = {2022}, author = {Bae, J and Park, K and Kim, YM}, title = {Commensal Microbiota and Cancer Immunotherapy: Harnessing Commensal Bacteria for Cancer Therapy.}, journal = {Immune network}, volume = {22}, number = {1}, pages = {e3}, doi = {10.4110/in.2022.22.e3}, pmid = {35291651}, issn = {1598-2629}, abstract = {Cancer is one of the leading causes of death worldwide and the number of cancer patients is expected to continuously increase in the future. Traditional cancer therapies focus on inhibiting cancer growth while largely ignoring the contribution of the immune system in eliminating cancer cells. Recently, better understanding of immunological mechanisms pertaining to cancer progress has led to development of several immunotherapies, which revolutionized cancer treatment. Nonetheless, only a small proportion of cancer patients respond to immunotherapy and maintain a durable response. Among multiple factors contributing to the variability of immunotherapy response rates, commensal microbiota inhabiting patients have been identified as one of the most critical factors determining the success of immunotherapy. The functional diversity of microbiota differentially affects the host immune system and controls the efficacy of immunotherapy in individual cancer patients. Moreover, clinical studies have demonstrated that changing the gut microbiota composition by fecal microbiota transplantation in patients who failed a previous immunotherapy converts them to responders of the same therapy. Consequently, both academic and industrial researchers are putting extensive efforts to identify and develop specific bacteria or bacteria mixtures for cancer immunotherapy. In this review, we will summarize the immunological roles of commensal microbiota in cancer treatment and give specific examples of bacteria that show anticancer effect when administered as a monotherapy or as an adjuvant agent for immunotherapy. We will also list ongoing clinical trials testing the anticancer effect of commensal bacteria.}, }
@article {pmid34514495, year = {2022}, author = {Sarbagili Shabat, C and Scaldaferri, F and Zittan, E and Hirsch, A and Mentella, MC and Musca, T and Cohen, NA and Ron, Y and Fliss Isakov, N and Pfeffer, J and Yaakov, M and Fanali, C and Turchini, L and Masucci, L and Quaranta, G and Kolonimos, N and Godneva, A and Weinberger, A and Kopylov, U and Levine, A and Maharshak, N}, title = {Use of Faecal Transplantation with a Novel Diet for Mild to Moderate Active Ulcerative Colitis: The CRAFT UC Randomised Controlled Trial.}, journal = {Journal of Crohn's & colitis}, volume = {16}, number = {3}, pages = {369-378}, pmid = {34514495}, issn = {1876-4479}, support = {//Azrieli Foundation/ ; }, mesh = {Adult ; *Colitis, Ulcerative/drug therapy/surgery ; Colonoscopy ; Diet ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Remission Induction ; }, abstract = {BACKGROUND: We evaluated whether integration of novel diets for donors and patients, in addition to faecal transplantation [FT], could increase FT remission rate in refractory ulcerative colitis [UC].
METHODS: This was a blinded, randomised, controlled trial in adults with active UC, defined by a simple clinical colitis activity index [SCCAI] of ≥5 and ≤11 and endoscopic Mayo score 2-3, refractory to medication. Group 1 received free diet and single donor standard FT by colonoscopy on Day 1and rectal enemas on Days 2 and 14 without dietary conditioning of the donor. Group 2 received FT as above but with dietary pre-conditioning of the donor for 14 days and a UC Exclusion Diet [UCED] for the patients. Group 3 received the UCED alone. The primary endpoint was Week 8 clinical steroid-free remission, defined as SCCAI <3.
RESULTS: Of 96 planned patients, 62 were enrolled. Remission Week 8 Group 1 was 2/17 [11.8%], Group 2 was 4/19 [21.1%], Group 3 was 6/15 [40%] [non-significant]. Endoscopic remission Group 1 was 2/17 [12%], Group 2 was 3/19 [16%], Group 3 was 4/15 [27%] [Group 1 vs 3 p = 0.38]. Mucosal healing [Mayo 0] was achieved only in Group 3 [3/15, 20%] vs 0/36 FT patients [p = 0.022]. Exacerbation of disease occurred in 3/17 [17.6%] of Group 1, 4/19 [21.1%] of Group 2, and 1/15 [6.7%] of Group 3 [Group 2 vs 3, p = 0.35].
CONCLUSIONS: UCED alone appeared to achieve higher clinical remission and mucosal healing than single donor FT with or without diet. The study was stopped for futility by a safety monitoring board.}, }
@article {pmid35288507, year = {2022}, author = {Li, H and Wang, Y and Zhao, C and Liu, J and Zhang, L and Li, A}, title = {Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, doi = {10.1097/CM9.0000000000001885}, pmid = {35288507}, issn = {2542-5641}, abstract = {BACKGROUND: Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.
METHODS: TS mice model (TSMO) (n = 80) were established with 3,3'-iminodipropionitrile, and 80 mice were used as controls. Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS, or were given probiotics. Fecal specimens were collected 3 weeks after FMT. 16S rRNA sequencing, behavioral observation, and serum serotonin (5-HT) assay were performed. Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov (KS) tests.
RESULTS: A total of 18 discriminative microbial signatures (linear discriminant analysis score >3) that varied significantly between TS and healthy mice (CONH) were identified. A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed (P < 0.05). Compared with non-transplanted TSMO, the symptoms of those transplanted with feces from CONH were alleviated (W = 336, P = 0.046). In the probiotic and FMT experiments, the serum 5-HT levels significantly increased in TSMO that received probiotics (KS = 1.423, P = 0.035) and in those transplanted with feces from CONH (W = 336.5, P = 0.046) compared with TSMO without transplantation.
CONCLUSIONS: This study suggests that FMT may ameliorate TS by promoting 5-HT secretion, and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.}, }
@article {pmid35279084, year = {2022}, author = {Orenstein, R and Dubberke, ER and Khanna, S and Lee, CH and Yoho, D and Johnson, S and Hecht, G and DuPont, HL and Gerding, DN and Blount, KF and Mische, S and Harvey, A}, title = {Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial.}, journal = {BMC infectious diseases}, volume = {22}, number = {1}, pages = {245}, pmid = {35279084}, issn = {1471-2334}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; *Microbiota ; Neoplasm Recurrence, Local ; Prospective Studies ; Retrospective Studies ; }, abstract = {BACKGROUND: Effective treatment options for recurrent Clostridioides difficile infection (rCDI) are limited, with high recurrence rates associated with the current standard of care. Herein we report results from an open-label Phase 2 trial to evaluate the safety, efficacy, and durability of RBX2660-a standardized microbiota-based investigational live biotherapeutic-and a closely-matched historical control cohort.
METHODS: This prospective, multicenter, open-label Phase 2 study enrolled patients who had experienced either ≥ 2 recurrences of CDI, treated by standard-of-care antibiotic therapy, after a primary CDI episode, or ≥ 2 episodes of severe CDI requiring hospitalization. Participants received up to 2 doses of RBX2660 rectally administered with doses 7 days apart. Treatment success was defined as the absence of CDI diarrhea without the need for retreatment for 8 weeks after completing study treatment. A historical control group with matched inclusion and exclusion criteria was identified from a retrospective chart review of participants treated with standard-of-care antibiotics for recurrent CDI who matched key criteria for the study. The primary objective was to compare treatment success of RBX2660 to the historical control group. A key secondary outcome was the safety profile of RBX2660, including adverse events and CDI occurrence through 24 months after treatment. In addition, fecal samples from RBX2660-treated participants were sequenced to evaluate microbiome composition and functional changes from before to after treatment.
RESULTS: In this Phase 2 open-label clinical trial, RBX2660 demonstrated a 78.9% (112/142) treatment success rate compared to a 30.7% (23/75) for the historical control group (p < 0.0001; Chi-square test). Post-hoc analysis indicated that 91% (88/97) of evaluable RBX2660 responders remained CDI occurrence-free to 24 months after treatment demonstrating durability. RBX2660 was well-tolerated with mostly mild to moderate adverse events. The composition and diversity of RBX2660 responders' fecal microbiome significantly changed from before to after treatment to become more similar to RBX2660, and these changes were durable to 24 months after treatment.
CONCLUSIONS: In this Phase 2 trial, RBX2660 was safe and effective for reducing rCDI recurrence as compared to a historical control group. Microbiome changes are consistent with restorative changes implicated in resisting C. difficile recurrence. Clinical Trials Registration NCT02589847 (10/28/2015).}, }
@article {pmid35105621, year = {2022}, author = {Chen, Y and Xueying, Z and Jiaqu, C and Qiyi, C and Huanlong, Q and Ning, L and Yasong, D and Xiaoxin, Z and Rong, Y and Jubao, L and Xiaoqiong, L and Chunlian, M and Yu, W and Shidong, C and Guifang, K and Dongmei, Z and Shuanfeng, F and Xujing, Z and Binrang, Y and Yanxia, W and Ling, L and Song, Y and Xiang, Z and Beihua, Z and Lin, J and Hong, J and , }, title = {FTACMT study protocol: a multicentre, double-blind, randomised, placebo-controlled trial of faecal microbiota transplantation for autism spectrum disorder.}, journal = {BMJ open}, volume = {12}, number = {1}, pages = {e051613}, pmid = {35105621}, issn = {2044-6055}, mesh = {*Autism Spectrum Disorder/etiology/therapy ; Child ; Child, Preschool ; Double-Blind Method ; Fecal Microbiota Transplantation/methods ; Feces ; *Gastrointestinal Microbiome ; Humans ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: Autism spectrum disorder (ASD) is a complicated diffuse developmental disorder that commonly involves gastrointestinal distress and dysbacteriosis. Emerging lines of evidence have shown faecal microbiota transplantation (FMT) to be a potential therapeutic strategy for improving the clinical outcomes of patients with ASD by re-establishing their intestinal microflora. We are undertaking the first-ever multicentre, double-blind, randomised controlled trial of FMT for the treatment of children with both ASD and gastrointestinal symptoms and will assess the feasibility and efficacy outcomes of this strategy.
METHODS: In total, 318 children with both ASD and gastrointestinal symptoms will be enrolled (from 15 hospitals in China) to receive either FMT intervention (n=212) or a placebo (control, n=106). Children aged 3-6 years will take two capsules two times a day, and those older than 6 years will take three capsules two times a day. Each patient will receive four treatment courses, with each 12-day course being repeated every month. Outcomes will be evaluated at baseline, throughout the period of intervention, and at subsequent follow-ups for 2 months. The primary trial objective is to investigate the remodelling effect of FMT on the intestinal microflora in patients with ASD. The secondary objective focuses on the clinical efficacy and safety of FMT, including its improvement of the clinical response and metabonomics.
ETHICS AND DISSEMINATION: Ethical approval was obtained from the hospital Ethics Committee of each Faecal Transfer for ASD China Multicenter Trial Working Group. The ongoing FMT clinical trial is intended to support the approval of the new technology and its administration. The results of this trial will provide high-quality evidence to inform the future clinical application of this new therapy.
TRIAL REGISTRATION NUMBER: ChiCTR2100043906; Pre-results.}, }
@article {pmid35286970, year = {2022}, author = {Vellingiri, B and Aishwarya, SY and Benita Jancy, S and Sriram Abhishek, G and Winster Suresh Babu, H and Vijayakumar, P and Narayanasamy, A and Mariappan, S and Sangeetha, R and Valsala Gopalakrishnan, A and Parthasarathi, R and Iyer, M}, title = {An anxious relationship between Autism Spectrum Disorder and Gut Microbiota: A tangled chemistry?.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {99}, number = {}, pages = {169-189}, doi = {10.1016/j.jocn.2022.03.003}, pmid = {35286970}, issn = {1532-2653}, abstract = {Autism spectrum disorder (ASD) is a serious multifactorial neurodevelopmental disorder often accompanied by strained social communication, repetitive behaviour, immune dysregulation, and gastrointestinal (GI) issues. Recent studies have recorded a link between dysbiosis in the gut microbiota (gm) and the primary stages of ASD. A bidirectional connection (also called microbiota-gut-brain-axis) exchanges information between the gut bacteria and central nervous system. When the homeostasis of the microenvironment of the gut is dysregulated, it causes oxidative stress, affecting neuronal cells and neurotransmitters, thereby causing neurodevelopmental disorders. Studies have confirmed a difference in the constitution of gut bacteria among ASD cases and their controls. Numerous studies on animal models of ASD have shown altered gm and its association with abnormal metabolite profile and altered behaviour phenotype. This process happens due to an abnormal metabolite production in gm, leading to changes in the immune system, especially in ASD. Hence, this review aims to question the current knowledge on gm dysbiosis and its related GI discomforts and ASD behavioural symptoms and shed light on the possible therapeutic approaches available to deal with this situation. Thereby, though it is understood that more research might be needed to prove an association or causal relationship between gm and ASD, therapy with the microbiome may also be considered as an effective strategy to combat this issue.}, }
@article {pmid35279514, year = {2022}, author = {Xu, J and Liu, C and Shi, K and Sun, X and Song, C and Xu, K and Liu, Y}, title = {Atractyloside-A ameliorates spleen deficiency diarrhea by interfering with TLR4/MyD88/NF-κB signaling activation and regulating intestinal flora homeostasis.}, journal = {International immunopharmacology}, volume = {107}, number = {}, pages = {108679}, doi = {10.1016/j.intimp.2022.108679}, pmid = {35279514}, issn = {1878-1705}, abstract = {PURPOSE: Spleen deficiency diarrhea (SDD) is one of the most common types of diarrhea and is linked to intestinal barrier dysfunction and intestinal flora disorders. Atractyloside-A (AA) is one of the main components of Atractylodes Lancea(Thunb.) DC., which acts on the gastrointestinal tract and has therapeutic effects on diarrhea. Folium sennae is a medicinal plant inducing diarrhea; thus, it is one of the effective methods to obtain a diarrhea model. However, the mechanism of action of AA in the treatment of SDD induced by Folium sennae is unclear.
METHODS: The intestinal thrapeutic effect of AA on SDD in mice was evaluated by colon pathology. RNA sequencing (RNA-seq) was used to analyze the colonic transcriptome profiles. In addition, 16S rDNA sequencing and fecal microbiota transplantation (FMT) were carried out to verify the role of AA in the regulation of the intestinal flora.
RESULTS: The findings revealed that AA alleviated SDD by ameliorating the pathological symptoms while suppressing intestinal inflammatory responses through the TLR4/MyD88/NF-kB signaling and reversing the impairment of mucin synthesis. Furthermore, AA improved the integrity of the intestinal barrier. RNA-seq identified 436 common DEGs out of 1033 DEGs between SDD and AA, and 1933 DEGs between SDD and Ctrl, which are highly enriched in the NF-κB and TNF pathways. Moreover, AA altered the composition of the intestinal flora and FMT reduced SDD.
CONCLUSION: AA exerted a therapeutic effect on SDD through the regulation of the intestinal flora and the inflammation by interfering with the TLR4/MyD88/NF-κB signaling pathway.}, }
@article {pmid35277036, year = {2022}, author = {Upreti, D and Ishiguro, S and Robben, N and Nakashima, A and Suzuki, K and Comer, J and Tamura, M}, title = {Oral Administration of Water Extract from Euglena gracilis Alters the Intestinal Microbiota and Prevents Lung Carcinoma Growth in Mice.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/nu14030678}, pmid = {35277036}, issn = {2072-6643}, support = {2018 CVM-SMILE//Kansas State University/ ; N/A//Euglena Research Fund/ ; 2020 JCRC-CRA//Kansas State University/ ; P20 GM103418/GM/NIGMS NIH HHS/United States ; DMR-1945589//National Science Foundation/ ; }, abstract = {The antitumor effects of a partially purified water extract from Euglena gracilis (EWE) and EWE treated by boiling (bEWE) were evaluated using orthotopic lung cancer syngeneic mouse models with Lewis lung carcinoma (LLC) cells. Daily oral administration of either EWE or bEWE started three weeks prior to the inoculation of LLC cells significantly attenuated tumor growth as compared to the phosphate buffered saline (PBS) control, and the attenuation was further enhanced by bEWE. The intestinal microbiota compositions in both extract-treated groups were more diverse than that in the PBS group. Particularly, a decrease in the ratio of Firmicutes to Bacteroidetes and significant increases in Akkermansia and Muribaculum were observed in two types of EWE-treated groups. Fecal microbiota transplantation (FMT) using bEWE-treated mouse feces attenuated tumor growth to an extent equivalent to bEWE treatment, while tumor growth attenuation by bEWE was abolished by treatment with an antibiotic cocktail. These studies strongly suggest that daily oral administration of partially purified water extracts from Euglena gracilis attenuates lung carcinoma growth via the alteration of the intestinal microbiota.}, }
@article {pmid35277027, year = {2022}, author = {Varesi, A and Pierella, E and Romeo, M and Piccini, GB and Alfano, C and Bjørklund, G and Oppong, A and Ricevuti, G and Esposito, C and Chirumbolo, S and Pascale, A}, title = {The Potential Role of Gut Microbiota in Alzheimer's Disease: From Diagnosis to Treatment.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/nu14030668}, pmid = {35277027}, issn = {2072-6643}, abstract = {Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer's Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease.}, }
@article {pmid35276971, year = {2022}, author = {Abujamel, TS and Al-Otaibi, NM and Abuaish, S and AlHarbi, RH and Assas, MB and Alzahrani, SA and Alotaibi, SM and El-Ansary, A and Aabed, K}, title = {Different Alterations in Gut Microbiota between Bifidobacterium longum and Fecal Microbiota Transplantation Treatments in Propionic Acid Rat Model of Autism.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/nu14030608}, pmid = {35276971}, issn = {2072-6643}, support = {RGP-1441-0027//Deanship of Scientific Research, Princess Nora Bint Abdulrahman University/ ; }, abstract = {Autism spectrum disorders (ASD) consist of a range of neurodevelopmental conditions accompanied by dysbiosis of gut microbiota. Therefore, a number of microbiota manipulation strategies were developed to restore their balance. However, a comprehensive comparison of the various methods on gut microbiota is still lacking. Here, we evaluated the effect of Bifidobacterium (BF) treatment and fecal microbiota transplantation (FT) on gut microbiota in a propionic acid (PPA) rat model of autism using 16S rRNA sequencing. Following PPA treatment, gut microbiota showed depletion of Bacteroidia and Akkermansia accompanied by a concomitant increase of Streptococcus, Lachnospiraceae, and Paraeggerthella. The dysbiosis was predicted to cause increased levels of porphyrin metabolism and impairments of acyl-CoA thioesterase and ubiquinone biosynthesis. On the contrary, BF and FT treatments resulted in a distinct increase of Clostridium, Bifidobacterium, Marvinbryantia, Butyricicoccus, and Dorea. The taxa in BF group positively correlated with vitamin B12 and flagella biosynthesis, while FT mainly enriched flagella biosynthesis. In contrast, BF and FT treatments negatively correlated with succinate biosynthesis, pyruvate metabolism, nitrogen metabolism, beta-Lactam resistance, and peptidoglycan biosynthesis. Therefore, the present study demonstrated that BF and FT treatments restored the PPA-induced dysbiosis in a treatment-specific manner.}, }
@article {pmid35276821, year = {2022}, author = {Prosperi, M and Santocchi, E and Guiducci, L and Frinzi, J and Morales, MA and Tancredi, R and Muratori, F and Calderoni, S}, title = {Interventions on Microbiota: Where Do We Stand on a Gut-Brain Link in Autism? A Systematic Review.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/nu14030462}, pmid = {35276821}, issn = {2072-6643}, support = {2757130//Ricerca Corrente, and the "5 × 1000" voluntary contributions, Italian Ministry of Health/ ; }, abstract = {The alteration of the microbiota-gut-brain axis has been recently recognized as a critical modulator of neuropsychiatric health and a possible factor in the etiopathogenesis of autism spectrum disorders (ASD). This systematic review offers practitioners an overview of the potential therapeutic options to modify dysbiosis, GI symptoms, and ASD severity by modulating the microbiota-gut-brain axis in ASD, taking into consideration limits and benefits from current findings. Comprehensive searches of PubMed, Scopus, the Web of Science Core Collection, and EMBASE were performed from 2000 to 2021, crossing terms referred to ASD and treatments acting on the microbiota-gut-brain axis. A total of 1769 publications were identified, of which 19 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Despite the encouraging findings, considering the variability of the treatments, the samples size, the duration of treatment, and the tools used to evaluate the outcome of the examined trials, these results are still partial. They do not allow to establish a conclusive beneficial effect of probiotics and other interventions on the symptoms of ASD. In particular, the optimal species, subspecies, and dosages have yet to be identified. Considering the heterogeneity of ASD, double-blind, randomized, controlled trials and treatment tailored to ASD characteristics and host-microbiota are recommended.}, }
@article {pmid33914709, year = {2021}, author = {Chaves, LD and Abyad, S and Honan, AM and Bryniarski, MA and McSkimming, DI and Stahura, CM and Wells, SC and Ruszaj, DM and Morris, ME and Quigg, RJ and Yacoub, R}, title = {Unconjugated p-cresol activates macrophage macropinocytosis leading to increased LDL uptake.}, journal = {JCI insight}, volume = {6}, number = {11}, pages = {}, pmid = {33914709}, issn = {2379-3708}, support = {UL1 TR001412/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Aorta/drug effects/*metabolism/pathology ; Cholesterol/metabolism ; Cholesterol, LDL/drug effects/*metabolism ; Coronary Artery Disease/*metabolism/pathology ; Coronary Vessels/drug effects/metabolism/pathology ; Cresols/*metabolism/pharmacology ; Diet, High-Fat ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Kidney Failure, Chronic/metabolism/microbiology ; Liver/drug effects/*metabolism/pathology ; Macrophages/drug effects/*metabolism ; Mice ; Pinocytosis/drug effects/*physiology ; Renal Insufficiency, Chronic/*metabolism/microbiology ; Triglycerides/metabolism ; }, abstract = {Patients with chronic kidney disease (CKD) and end-stage renal disease suffer from increased cardiovascular events and cardiac mortality. Prior studies have demonstrated that a portion of this enhanced risk can be attributed to the accumulation of microbiota-derived toxic metabolites, with most studies focusing on the sulfonated form of p-cresol (PCS). However, unconjugated p-cresol (uPC) itself was never assessed due to rapid and extensive first-pass metabolism that results in negligible serum concentrations of uPC. These reports thus failed to consider the host exposure to uPC prior to hepatic metabolism. In the current study, not only did we measure the effect of altering the intestinal microbiota on lipid accumulation in coronary arteries, but we also examined macrophage lipid uptake and handling pathways in response to uPC. We found that atherosclerosis-prone mice fed a high-fat diet exhibited significantly higher coronary artery lipid deposits upon receiving fecal material from CKD mice. Furthermore, treatment with uPC increased total cholesterol, triglycerides, and hepatic and aortic fatty deposits in non-CKD mice. Studies employing an in vitro macrophage model demonstrated that uPC exposure increased apoptosis whereas PCS did not. Additionally, uPC exhibited higher potency than PCS to stimulate LDL uptake and only uPC induced endocytosis- and pinocytosis-related genes. Pharmacological inhibition of varying cholesterol influx and efflux systems indicated that uPC increased macrophage LDL uptake by activating macropinocytosis. Overall, these findings indicate that uPC itself had a distinct effect on macrophage biology that might have contributed to increased cardiovascular risk in patients with CKD.}, }
@article {pmid35275989, year = {2022}, author = {Aby, ES and Vaughn, BP and Enns, EA and Rajasingham, R}, title = {Cost-effectiveness of fecal microbiota transplantation for first recurrent Clostridioides difficile infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciac207}, pmid = {35275989}, issn = {1537-6591}, abstract = {BACKGROUND: Both the American College of Gastroenterology and the Infectious Disease Society of America (IDSA) / Society of Healthcare Epidemiology of American 2021 Clostridioides difficile infection (CDI) guidelines recommend fecal microbiota transplantation (FMT) for persons with multiple recurrent CDI. Emerging data suggest that FMT may have high cure rates when used for first recurrent CDI. The aim of this study was to assess the cost-effectiveness of FMT for first recurrent CDI.
METHODS: We developed a Markov model to simulate a cohort of patients presenting with initial CDI infection. The model estimated the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the 2021 IDSA guidelines, with the additional option of FMT for first recurrent CDI. The model includes stratification by the severity of initial infection, estimates of cure, recurrence, and mortality. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).
RESULTS: When FMT is available for first recurrent CDI, the optimal cost-effective treatment strategy is fidaxomicin for initial non-severe CDI, Vancomycin for initial severe CDI, and FMT for first and subsequent recurrent CDI, with an ICER of $27,135/QALY. In probabilistic sensitivity analysis at a $100,000 cost-effectiveness threshold, FMT for first and subsequent CDI recurrence was cost-effective 90% of the time given parameter uncertainty.
CONCLUSIONS: FMT is a cost-effective strategy for first recurrent CDI. Prospective evaluation of FMT for first recurrent CDI is warranted to determine the efficacy and risk of recurrence.}, }
@article {pmid35273972, year = {2022}, author = {Ishikawa, D and Zhang, X and Nomura, K and Seki, N and Haraikawa, M and Haga, K and Shibuya, T and Kim, YG and Nagahara, A}, title = {A Randomized Placebo-Controlled Trial of Combination Therapy With Post-triple-antibiotic-therapy Fecal Microbiota Transplantation and Alginate for Ulcerative Colitis: Protocol.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {779205}, doi = {10.3389/fmed.2022.779205}, pmid = {35273972}, issn = {2296-858X}, abstract = {Background: Fecal microbiota transplantation (FMT) has been widely performed for ulcerative colitis (UC) treatment at the clinical trial stage. Previous reports have used multiple FMT methods to enhance the colonization of healthy donor microbiota in the recipient's intestines. FMT following triple antibiotic therapy with amoxicillin, fosfomycin, and metronidazole (A-FMT) is not only effective but also requires only one FMT, which improves dysbiosis caused by reduced Bacteroidetes diversity in patients with UC. Alginate and its derivatives have the potential to induce the growth of intestinal bacteria including Bacteroides members and produce short-chain fatty acids (SCFAs), which are beneficial in regulating overactive autoimmunity. Our trial aims to investigate whether post-intervention with alginate, which can improve the intestinal environment, will enhance the therapeutic effect of A-FMT in UC and increase the long-term remission rate.
Methods and Analysis: This trial is a double-blinded, randomized, placebo-controlled, parallel assignment trial. Patients with UC and fecal donation candidates will undergo strict screening before being involved in the trial. Eligible patients are randomly divided into two groups: one group will drink one bottle of alginate twice a day for 8 consecutive weeks after A-FMT, while the other group will take a placebo instead of the alginate drink. The primary endpoints are the changes in the Total Mayo Score at 8 weeks after study initiation and A-FMT from baseline. The secondary endpoint is the comparison of clinical features, microbiota, and metabolomic analysis before and after 8 weeks of study food intake. Changes at 6, 12, 18, and 24 months after A-FMT will be assessed. Finally, a subpopulation analysis of the relationship between patients and donors is an exploratory endpoint.
Discussion: The FMT post-treatment used in this study is an oral alginate drink that is easily accepted by patients. If the regimen achieves the desired results, it can further improve the A-FMT regimen and provide evidence for clinical practice guidelines for UC.
Clinical Trial Registration: https://jrct.niph.go.jp/latest-detail/jRCTs031200103, identifier: jRCTs031200103.}, }
@article {pmid35273587, year = {2022}, author = {Chen, Y and Song, S and Shu, A and Liu, L and Jiang, J and Jiang, M and Wu, Q and Xu, H and Sun, J}, title = {The Herb Pair Radix Rehmanniae and Cornus Officinalis Attenuated Testicular Damage in Mice With Diabetes Mellitus Through Butyric Acid/Glucagon-Like Peptide-1/Glucagon-Like Peptide-1 Receptor Pathway Mediated by Gut Microbiota.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {831881}, doi = {10.3389/fmicb.2022.831881}, pmid = {35273587}, issn = {1664-302X}, abstract = {Growing body of research indicates that Traditional Chinese Medicine (TCM) interact with gut microbiota (GM) after oral administration. Radix Rehmanniae and Cornus Officinalis (RR-CO), a well-known TCM pair, is often used to treat diabetes mellitus (DM) and its complications. The current study aimed to explore the protective effects of RR-CO on DM induced testicular damage by modulating GM. The RR-CO treatments significantly reduced hyperglycemia, ameliorated testicular ultrastructural damage and inflammation in DM model to varying degrees. Additionally, 16S-ribosomal DNA (rDNA) sequencing results showed that RR-CO treatment increased the amount of butyric acid-producing GM, such as Clostridiaceae_1 family, and decreased the abundance of Catabacter, Marvinbryantia, and Helicobacter genera. RR-CO fecal bacteria transplantation (RC-FMT) increased the abundance of Clostridiaceae_1 in the Model FMT (M-FMT) group and ameliorated testicular damage. Furthermore, treatment with RR-CO increased the fecal butyric acid level, serum Glucagon-like peptide-1 (GLP-1) level, and testicular GLP-1 receptor (GLP-1R) expression compared to those in DM mice. Finally, intraperitoneal administration of sodium butyrate (SB) significantly improved the pathological damage to the testis and reduced inflammation in the DM group. These data demonstrated a protective effect of RR-CO on DM-induced testicular damage by modulation of GM, which may be mediated by the butyric acid/GLP/GLP-1R pathway.}, }
@article {pmid35271405, year = {2022}, author = {Rotz, SJ and Sangwan, N and Nagy, M and Tzeng, A and Jia, M and Moncaliano, M and Majhail, NS and Eng, C}, title = {Fecal microbiota of adolescent and young adult cancer survivors and metabolic syndrome: an exploratory study.}, journal = {Pediatric hematology and oncology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/08880018.2022.2049937}, pmid = {35271405}, issn = {1521-0669}, abstract = {Metabolic syndrome and obesity occur commonly in long-term pediatric cancer survivors. The intestinal microbiome is associated with metabolic syndrome and obesity in the general population, and is perturbed during cancer therapy. We aimed to determine if long-term survivors of pediatric cancer would have reduced bacterial microbiome diversity, and if these findings would be associated with components of the metabolic syndrome, obesity, and chronic inflammation. We performed a cross-sectional exploratory study examining the intestinal microbiome via 16S amplicon sequencing, treatment history, clinical measurements (blood pressure, body mass index) and biomarkers (hemoglobin A1c, lipoproteins, adiponectin: leptin ratio, C-reactive protein, TNFα, Interleukin-6, and Interleukin-10) between 35 long-term survivors and 32 age, sex, and race matched controls. All subjects were aged 10-40 years, and survivors were at least five years from therapy completion. Survivors had lower alpha diversity compared to controls (Shannon index p = .001, Simpson index p = .032) and differently abundant bacterial taxa. Further, among survivors, those who received radiation (18/35) to the central nervous system or abdomen/pelvis had decreased alpha diversity compared to those who did not receive radiation (Shannon and Simpson p < .05 for both). Although, no specific component of metabolic syndrome or cytokine was associated with measures of alpha diversity, survivors with low adiponectin-lectin ratio, elevated body mass index, and elevated C-reactive protein had differently abundant taxa compared to those with normal measures. The microbiome of cancer survivors remains less diverse than controls even many years after diagnosis, and exposure to radiation may lead to further loss of diversity in survivors.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2049937.}, }
@article {pmid35269538, year = {2022}, author = {Li, Z and Li, Y and Sun, Q and Wei, J and Li, B and Qiu, Y and Liu, K and Shao, D and Ma, Z}, title = {Targeting the Pulmonary Microbiota to Fight against Respiratory Diseases.}, journal = {Cells}, volume = {11}, number = {5}, pages = {}, doi = {10.3390/cells11050916}, pmid = {35269538}, issn = {2073-4409}, abstract = {The mucosal immune system of the respiratory tract possesses an effective "defense barrier" against the invading pathogenic microorganisms; therefore, the lungs of healthy organisms are considered to be sterile for a long time according to the strong pathogens-eliminating ability. The emergence of next-generation sequencing technology has accelerated the studies about the microbial communities and immune regulating functions of lung microbiota during the past two decades. The acquisition and maturation of respiratory microbiota during childhood are mainly determined by the birth mode, diet structure, environmental exposure and antibiotic usage. However, the formation and development of lung microbiota in early life might affect the occurrence of respiratory diseases throughout the whole life cycle. The interplay and crosstalk between the gut and lung can be realized by the direct exchange of microbial species through the lymph circulation, moreover, the bioactive metabolites produced by the gut microbiota and lung microbiota can be changed via blood circulation. Complicated interactions among the lung microbiota, the respiratory viruses, and the host immune system can regulate the immune homeostasis and affect the inflammatory response in the lung. Probiotics, prebiotics, functional foods and fecal microbiota transplantation can all be used to maintain the microbial homeostasis of intestinal microbiota and lung microbiota. Therefore, various kinds of interventions on manipulating the symbiotic microbiota might be explored as novel effective strategies to prevent and control respiratory diseases.}, }
@article {pmid35268045, year = {2022}, author = {Li, W and Zhang, L and Xu, Q and Yang, W and Zhao, J and Ren, Y and Yu, Z and Ma, L}, title = {Taxifolin Alleviates DSS-Induced Ulcerative Colitis by Acting on Gut Microbiome to Produce Butyric Acid.}, journal = {Nutrients}, volume = {14}, number = {5}, pages = {}, doi = {10.3390/nu14051069}, pmid = {35268045}, issn = {2072-6643}, abstract = {Taxifolin is a bioflavonoid which has been used to treat Inflammatory Bowel Disease. However, taxifolin on DSS-induced colitis and gut health is still unclear. Here, we studied the effect of taxifolin on DSS-induced intestinal mucositis in mice. We measured the degree of intestinal mucosal injury and inflammatory response in DSS treated mice with or without taxifolin administration and studied the changes of fecal metabolites and intestinal microflora using 16S rRNA. The mechanism was further explored by fecal microbiota transplantation. The results showed that the weight loss and diarrhea score of the mice treated with taxifolin decreased in DSS-induced mice and longer colon length was displayed after taxifolin supplementation. Meanwhile, the expression of GPR41 and GPR43 in the colon was significantly increased by taxifolin treatment. Moreover, the expression of TNF-α, IL-1β, and IL-6 in colon tissue was inhibited by taxifolin treatment. The fecal metabolism pattern changed significantly after DSS treatment, which was reversed by taxifolin treatment. Importantly, taxifolin significantly increased the levels of butyric acid and isobutyric acid in the feces of DSS-treated mice. In terms of gut flora, taxifolin reversed the changes of Akkermansia, and further decreased uncultured_bacterium_f_Muribaculaceae. Fecal transplantation from taxifolin-treated mice showed a lower diarrhea score, reduced inflammatory response in the colon, and reduced intestinal mucosal damage, which may be related to the increased level of butyric acid in fecal metabolites. In conclusion, this study provides evidence that taxifolin can ameliorate DSS-induced colitis by altering gut microbiota to increase the production of SCFAs.}, }
@article {pmid35266816, year = {2022}, author = {He, S and Cui, S and Song, W and Jiang, Y and Chen, H and Liao, D and Lu, X and Li, J and Chen, X and Peng, L}, title = {Interleukin-17 Weakens the NAFLD/NASH Process by Facilitating Intestinal Barrier Restoration Depending on the Gut Microbiota.}, journal = {mBio}, volume = {}, number = {}, pages = {e0368821}, doi = {10.1128/mbio.03688-21}, pmid = {35266816}, issn = {2150-7511}, abstract = {Interleukin-17 (IL-17) is associated with nonalcoholic fatty liver disease (NAFLD) and gut microbiota, and how IL-17 mediates the NAFLD/nonalcoholic steatohepatitis (NASH) process depending on the gut microbiota is unclear. We found that T helper 17 (TH17) cells were decreased in the small intestine in a methionine choline-deficient (MCD) diet-induced NASH model. IL-17-deficient (Il17-/-) mice showed alterations in intestinal microbiota, including the inhibition of probiotic growth and the overgrowth of certain pathogenic bacteria, and were prone to higher endotoxemia levels and more severe gastrointestinal barrier defects than wild-type (WT) mice. Furthermore, TH17 cells were responsible for restoring the intestinal barrier after administration of recombinant IL-17 to Il17-/- mice or injection of CD4+ T cells into a Rag1-/- mouse model. Additionally, transplantation of the microbiota from WT mice to Il17-/- mice restored the intestinal barrier. Notably, microbiota-depleted Il17-/- mice were resistant to MCD diet-induced intestinal barrier impairment. Fecal microbiota transplantation from Il17-/- mice to microbiota-depleted mice aggravated intestinal barrier impairment and then promoted the development of NASH. Collectively, this study showed that host IL-17 could strengthen intestinal mucosal barrier integrity and reduce dysbiosis-induced intestinal injury and secondary extraintestinal organ injury induced by a special diet. IMPORTANCE The morbidity of NASH has increased, with limited effective treatment options. IL-17 plays a protective role in the gut mucosa in high-fat-diet (HFD)-related metabolic disorders, and HFD-related microbiota dysbiosis is responsible for a decreased number of T helper 17 (TH17) cells in the lamina propria. The mechanism by which IL-17 mediates the NAFLD/NASH process depending on the gut microbiota is unclear. In our study, IL-17 originating from TH17 cells maintained intestinal barrier integrity and determined the outcomes of diet-related disease, which may be a target strategy for NAFLD/NASH.}, }
@article {pmid35262957, year = {2022}, author = {Hu, C and Xu, B and Wang, X and Wan, WH and Lu, J and Kong, D and Jin, Y and You, W and Sun, H and Mu, X and Feng, D and Chen, Y}, title = {Gut microbiota-derived short-chain fatty acids regulates group 3 innate lymphoid cells in hepatocellular carcinoma.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.32449}, pmid = {35262957}, issn = {1527-3350}, abstract = {BACKGROUND AND AIMS: Type 3 innate lymphoid cells (ILC3s) are essential for host defense against infection and tissue homeostasis. However, its role in the development of hepatocellular carcinoma (HCC) has not been adequately confirmed. In this study, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) derived from intestinal microbiota in ILC3 regulation.
APPROACH AND RESULTS: Here, we reported that the Lactobacillus reuteri was markedly reduced in the gut microbiota of mice with hepatocellular carcinoma (HCC), accompanied by decreased short chain fatty acids (SCFAs) levels, especially acetate. Additionally, transplantation of fecal bacteria from wild type mice or Lactobacillus reuteri could promote an anticancer effect, elevate acetate level and reduce IL17A secretion in mice with HCC. Mechanistically, acetate reduced the production of IL17A in hepatic ILC3s through inhibiting histone deacetylase (HDAC) activity, increasing the acetylation of Sox13 in the site of K30 and decreasing expression of Sox13. Moreover, the combination of acetate with PD-1/PD-L1 blockade significantly enhanced anti-tumor immunity. Consistently, Tumor-infiltrating ILC3s correlated with negative prognosis in patients with HCC, which could be functionally mediated via acetate.
CONCLUSIONS: These findings suggested that modifying bacteria, changing SCFAs, reducing IL17A-producing ILC3s infiltration and combining with immune checkpoint inhibitors will contribute to the clinical treatment of HCC.}, }
@article {pmid35245613, year = {2022}, author = {Dong, S and Sun, M and He, C and Cheng, H}, title = {Brain-gut-microbiota axis in Parkinson's disease: A historical review and future perspective.}, journal = {Brain research bulletin}, volume = {183}, number = {}, pages = {84-93}, doi = {10.1016/j.brainresbull.2022.02.015}, pmid = {35245613}, issn = {1873-2747}, abstract = {Parkinson's disease (PD) is the second most common degenerative disease of the central nervous system (CNS) after Alzheimer's disease. In addition to the typical motor symptoms, the clinical manifestations of patients with PD include gastrointestinal symptoms, which even precede the motor symptoms. Recent research has found that the gut microbiota regulates the brain-gut axial interaction through immune, endocrine, and direct neural mechanisms, supporting the hypothesis that the pathological process of PD spreads from the gut to the brain. In this review article, we highlight the landmark findings in the field of PD, with particular attention to the brain-gut-microbiota axis. We summarize the changes and their clinical effects on the gut microbiota and metabolites observed in PD. The intestinal microbiota may contain appropriate targets for the prevention and treatment of PD. Clinical cohort studies suggest that certain intestinal microbes have protective or pathogenic effects on the progression of PD. A better understanding of the interaction between the gut-brain axis, the gut microbiota, and PD has the potential to lead to new diagnostic and therapeutic approaches. Animal experiments suggest that fecal microbiota transplantation (FMT) is helpful for treating PD, and FMT is expected to be an effective treatment for PD in the future.}, }
@article {pmid35259427, year = {2022}, author = {Vicentini, FA and Szamosi, JC and Rossi, L and Griffin, L and Nieves, K and Bihan, D and Lewis, IA and Pittman, QJ and Swain, MG and Surette, MG and Hirota, SA and Sharkey, KA}, title = {Colitis-associated microbiota drives changes in behaviour in male mice in the absence of inflammation.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2022.03.001}, pmid = {35259427}, issn = {1090-2139}, abstract = {Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. IBD are associated with a high prevalence of cognitive, behavioural and emotional comorbidities, including anxiety and depression. The link between IBD and the development of behavioural comorbidities is poorly understood. As the intestinal microbiota profoundly influences host behaviour, we sought to determine whether the altered gut microbiota associated with intestinal inflammation contributes to the development of behavioural abnormalities. Using the dextran sulphate sodium (DSS) model of colitis, we characterized intestinal inflammation, behaviour (elevated plus maze and tail suspension test) and the composition of the microbiota in male mice. Cecal contents from colitic mice were transferred into germ-free (GF) or antibiotic (Abx)-treated mice, and behaviour was characterized in recipient mice. Gene expression was measured using qPCR. DSS colitis was characterized by a significant reduction in body weight and an increase in colonic inflammatory markers. These changes were accompanied by increased anxiety-like behaviour, an altered gut microbiota composition, and increased central Tnf expression. Transfer of the cecal matter from colitic mice induced similar behavioural changes in both GF and Abx-treated recipient mice, with no signs of colonic or neuroinflammation. Upon characterization of the microbiota in donor and recipient mice, specific taxa were found to be associated with behavioural changes, notably members of the Lachnospiraceae family. Behavioural abnormalities associated with intestinal inflammation are transmissible via transfer of cecal matter, suggesting that alterations in the composition of the gut microbiota play a key role in driving behavioural changes in colitis.}, }
@article {pmid35258452, year = {2022}, author = {Zhang, X and Zhang, X and Tong, F and Cai, Y and Zhang, Y and Song, H and Tian, X and Yan, C and Han, Y}, title = {Gut microbiota induces high platelet response in patients with ST segment elevation myocardial infarction after ticagrelor treatment.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, doi = {10.7554/eLife.70240}, pmid = {35258452}, issn = {2050-084X}, support = {82170297//National Natural Science Foundation of China/ ; 82070300//National Natural Science Foundation of China/ ; }, abstract = {Background: Ticagrelor is a first-line drug for the treatment of acute ST elevation myocardial infarction (STEMI). However, approximately 20% STEMI patients taking ticagrelor exhibited a delayed response and the mechanism was still unclear.
Methods: To explore the mechanism of the poor response of ticagrelor in post-percutaneous coronary intervention (PCI) patients, we enrolled 65 high platelet reactivity (HPR) patients and 90 controls (normal platelet reactivity [NPR]). Pharmacokinetic assessment result showed that the plasma concentrations of ticagrelor and its metabolism production, AR-C124910XX, were lower in HPR patients than controls. Further single nucloetide polymorphism (SNP) analysis identified that there is no difference in ATP binding cassette subfamily B member 1 (ABCB1) gene expression between the NPR group and the HPR group. Metagenomic and metabolomic analyses of fecal samples showed that HPR patients had higher microbial richness and diversity. Transplantation of the gut microbiota from HPR donors to microbiota-depleted mice obviously decreased plasma concentration of ticagrelor.
Results: Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with STEMI and support that modify gut microbiota is a potential therapeutic option for STEMI.
Conclusions: Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with ST elevation myocardial infarction (STEMI) and support that modify gut microbiota is a potential therapeutic option for STEMI.
Funding: NSFC 82170297 and 82070300 from the National Natural Science Foundation of China.}, }
@article {pmid35255932, year = {2022}, author = {Gebrayel, P and Nicco, C and Al Khodor, S and Bilinski, J and Caselli, E and Comelli, EM and Egert, M and Giaroni, C and Karpinski, TM and Loniewski, I and Mulak, A and Reygner, J and Samczuk, P and Serino, M and Sikora, M and Terranegra, A and Ufnal, M and Villeger, R and Pichon, C and Konturek, P and Edeas, M}, title = {Microbiota medicine: towards clinical revolution.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {111}, pmid = {35255932}, issn = {1479-5876}, abstract = {The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrated, more than a decade ago, that the gut microbial alteration is a key factor in the pathogenesis of many local and systemic disorders. In this regard, a deep understanding of the mechanisms involved in the gut microbial symbiosis/dysbiosis is crucial for the clinical and health field. We review the most recent studies on the involvement of gut microbiota in the pathogenesis of many diseases. We also elaborate the different strategies used to manipulate the gut microbiota in the prevention and treatment of disorders. The future of medicine is strongly related to the quality of our microbiota. Targeting microbiota dysbiosis will be a huge challenge.}, }
@article {pmid35250668, year = {2022}, author = {Doll, JPK and Vázquez-Castellanos, JF and Schaub, AC and Schweinfurth, N and Kettelhack, C and Schneider, E and Yamanbaeva, G and Mählmann, L and Brand, S and Beglinger, C and Borgwardt, S and Raes, J and Schmidt, A and Lang, UE}, title = {Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression-Case Report.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {815422}, pmid = {35250668}, issn = {1664-0640}, abstract = {Depression is a debilitating disorder, and at least one third of patients do not respond to therapy. Associations between gut microbiota and depression have been observed in recent years, opening novel treatment avenues. Here, we present the first two patients with major depressive disorder ever treated with fecal microbiota transplantation as add-on therapy. Both improved their depressive symptoms 4 weeks after the transplantation. Effects lasted up to 8 weeks in one patient. Gastrointestinal symptoms, constipation in particular, were reflected in microbiome changes and improved in one patient. This report suggests further FMT studies in depression could be worth pursuing and adds to awareness as well as safety assurance, both crucial in determining the potential of FMT in depression treatment.}, }
@article {pmid35252301, year = {2022}, author = {Yao, Q and Fan, L and Zheng, N and Blecker, C and Delcenserie, V and Li, H and Wang, J}, title = {2'-Fucosyllactose Ameliorates Inflammatory Bowel Disease by Modulating Gut Microbiota and Promoting MUC2 Expression.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {822020}, doi = {10.3389/fnut.2022.822020}, pmid = {35252301}, issn = {2296-861X}, abstract = {Gut microbiota dysbiosis, together with goblet cells dysfunction has been observed in ulcerative colitis cases. This study aims to evaluate the potential of 2'-fucosyllactose (2'-FL) supplementation in inhibiting intestinal inflammation through regulating gut microbiota, protecting goblet cells, and stimulating mucin secretion. 2'-FL was orally administered to C57BL/6J mice daily (400 mg/kg bw) for 21 days and 5% dextran sulfate sodium (DSS) was used to induce the colitis in the last 7 days. Meanwhile, fecal microbiota transplantation (FMT) was conducted to test the roles of gut microbiota in the remission of colitis by 2'-FL. Gut microbiota alteration was analyzed through 16S ribosomal RNA (16S rRNA) sequencing. Periodic acid-Schiff (PAS), immunofluorescence staining, as well as mucin 2 (MUC2) and NOD-like receptor family pyrin domain containing 6 (NLRP6) messenger RNA (mRNA) expression in colon fragments was performed and detected. The results showed that the DSS + 2'-FL mice were found to have a slower rate of weight loss, lower disease activity index (DAI) scores, and longer colon lengths than the DSS group (p < 0.05), so in the FMT recipient mice which received fecal microbiota from the DSS + 2'-FL group. In addition, the data revealed that 2'-FL relieved the disorder of DSS-induced gut microbiota, including decreasing the high abundance of mucin-utilizing bacteria in the DSS group, such as Bacteroides, Lachnospiraceae NK4A136, Lachnospiraceae, and Bacteroides vulgatus. PAS and immunofluorescence staining showed that 2'-FL treatment promoted the recovery of goblet cells and enhanced MUC2 and NLRP6 expression, which was also observed in the FM (DSS + 2'-FL) group. Moreover, NLRP6, which has been proved to be a negative regulator for Toll-like receptor 4/myeloid differential protein-8/nuclear factor-kappa B (TLR4/MyD88/NF-κB) pathway, was upregulated by 2'-FL in colon tissue. In conclusion, this study suggests that 2'-FL ameliorates colitis in a gut microbiota-dependent manner. The underlying protective mechanism associates with the recovery of goblet cells number and improves MUC2 secretion through TLR4-related pathway.}, }
@article {pmid35243943, year = {2022}, author = {Zhao, Y and Li, M and Wang, Y and Geng, R and Fang, J and Liu, Q and Kang, SG and Zeng, WC and Huang, K and Tong, T}, title = {Understanding the mechanism underlying the anti-diabetic effect of dietary component: a focus on gut microbiota.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-21}, doi = {10.1080/10408398.2022.2045895}, pmid = {35243943}, issn = {1549-7852}, abstract = {Diabetes has become one of the biggest non-communicable diseases and threatens human health worldwide. The management of diabetes is a complex and multifaceted process including drug therapy and lifestyle interventions. Dietary components are essential for both diabetes management and health and survival of trillions of the gut microbiota (GM). Herein, we will discuss the relationship between diets and GM, the mechanism linking diabetes and gut dysbiosis, and the effects of dietary components (nutrients, phytochemicals, probiotics, food additives, etc.) on diabetes from the perspective of modulating GM. The GM of diabetic patients differs from that of health individuals and GM disorder contributes to the onset and maintenance of diabetes. Studies in humans and animal models consolidate that dietary component is a key regulator of diabetes and increasing evidence suggests that the alteration of GM plays a salient role in dietary interventions for diabetes. Given that diabetes is a major public health issue, especially that diabetes is linked with a high risk of mortality from COVID-19, this review provides compelling evidence for that targeting GM by dietary components is a promising strategy, and offers new insights into potential preventive or therapeutic approaches (dietary and pharmacological intervention) for the clinical management of diabetes.}, }
@article {pmid35242797, year = {2022}, author = {Zhang, T and Gao, G and Sakandar, HA and Kwok, LY and Sun, Z}, title = {Gut Dysbiosis in Pancreatic Diseases: A Causative Factor and a Novel Therapeutic Target.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {814269}, doi = {10.3389/fnut.2022.814269}, pmid = {35242797}, issn = {2296-861X}, abstract = {Pancreatic-related disorders such as pancreatitis, pancreatic cancer, and type 1 diabetes mellitus (T1DM) impose a substantial challenge to human health and wellbeing. Even though our understanding of the initiation and progression of pancreatic diseases has broadened over time, no effective therapeutics is yet available for these disorders. Mounting evidence suggests that gut dysbiosis is closely related to human health and disease, and pancreatic diseases are no exception. Now much effort is under way to explore the correlation and eventually potential causation between the gut microbiome and the course of pancreatic diseases, as well as to develop novel preventive and/or therapeutic strategies of targeted microbiome modulation by probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT) for these multifactorial disorders. Attempts to dissect the intestinal microbial landscape and its metabolic profile might enable deep insight into a holistic picture of these complex conditions. This article aims to review the subtle yet intimate nexus loop between the gut microbiome and pancreatic diseases, with a particular focus on current evidence supporting the feasibility of preventing and controlling pancreatic diseases via microbiome-based therapeutics and therapies.}, }
@article {pmid35242721, year = {2022}, author = {Zhou, Z and Sun, B and Yu, D and Zhu, C}, title = {Gut Microbiota: An Important Player in Type 2 Diabetes Mellitus.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {834485}, doi = {10.3389/fcimb.2022.834485}, pmid = {35242721}, issn = {2235-2988}, abstract = {Type 2 diabetes mellitus (T2DM) is one of the common metabolic diseases in the world. Due to the rise in morbidity and mortality, it has become a global health problem. To date, T2DM still cannot be cured, and its intervention measures mainly focus on glucose control as well as the prevention and treatment of related complications. Interestingly, the gut microbiota plays an important role in the development of metabolic diseases, especially T2DM. In this review, we introduce the characteristics of the gut microbiota in T2DM population, T2DM animal models, and diabetic complications. In addition, we describe the molecular mechanisms linking host and the gut microbiota in T2DM, including the host molecules that induce gut microbiota dysbiosis, immune and inflammatory responses, and gut microbial metabolites involved in pathogenesis. These findings suggest that we can treat T2DM and its complications by remodeling the gut microbiota through interventions such as drugs, probiotics, prebiotics, fecal microbiota transplantation (FMT) and diets.}, }
@article {pmid35241180, year = {2022}, author = {Hu, J and Deng, F and Zhao, B and Lin, Z and Sun, Q and Yang, X and Wu, M and Qiu, S and Chen, Y and Yan, Z and Luo, S and Zhao, J and Liu, W and Li, C and Liu, KX}, title = {Lactobacillus murinus alleviate intestinal ischemia/reperfusion injury through promoting the release of interleukin-10 from M2 macrophages via Toll-like receptor 2 signaling.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {38}, pmid = {35241180}, issn = {2049-2618}, support = {81730058//National Natural Science Foundation of China/ ; 81671955//National Natural Science Foundation of China/ ; 82902010//National Natural Science Foundation of China/ ; 2021M701611//China Postdoctoral Science Foundation/ ; }, abstract = {BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury has high morbidity and mortality rates. Gut microbiota is a potential key factor affecting intestinal I/R injury. Populations exhibit different sensitivities to intestinal I/R injury; however, whether this interpopulation difference is related to variation in gut microbiota is unclear. Here, to elucidate the interaction between the gut microbiome and intestinal I/R injury, we performed 16S DNA sequencing on the preoperative feces of C57BL/6 mice and fecal microbiota transplantation (FMT) experiments in germ-free mice. The transwell co-culture system of small intestinal organoids extracted from control mice and macrophages extracted from control mice or Toll-like receptor 2 (TLR2)-deficient mice or interleukin-10 (IL-10)-deficient mice were established separately to explore the potential mechanism of reducing intestinal I/R injury.
RESULTS: Intestinal I/R-sensitive (Sen) and intestinal I/R-resistant (Res) mice were first defined according to different survival outcomes of mice suffering from intestinal I/R. Fecal microbiota composition and diversity prior to intestinal ischemia differed between Sen and Res mice. The relative abundance of Lactobacillus murinus (L. murinus) at the species level was drastically higher in Res than that in Sen mice. Clinically, the abundance of L. murinus in preoperative feces of patients undergoing cardiopulmonary bypass surgery was closely related to the degree of intestinal I/R injury after surgery. Treatment with L. murinus significantly prevented intestinal I/R-induced intestinal injury and improved mouse survival, which depended on macrophages involvement. Further, in vitro experiments indicated that promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury.
CONCLUSION: The gut microbiome is involved in the postoperative outcome of intestinal I/R. Lactobacillus murinus alleviates mice intestinal I/R injury through macrophages, and promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury. This study revealed a novel mechanism of intestinal I/R injury and a new therapeutic strategy for clinical practice. Video Abstract.}, }
@article {pmid35237276, year = {2022}, author = {Yang, Y and Zheng, X and Wang, Y and Tan, X and Zou, H and Feng, S and Zhang, H and Zhang, Z and He, J and Cui, B and Zhang, X and Wu, Z and Dong, M and Cheng, W and Tao, S and Wei, H}, title = {Human Fecal Microbiota Transplantation Reduces the Susceptibility to Dextran Sulfate Sodium-Induced Germ-Free Mouse Colitis.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {836542}, pmid = {35237276}, issn = {1664-3224}, abstract = {In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including Alistipes putredinis, Akkermansia muciniphila, Bifidobacterium adolescentis, short-chain fatty acids (SCFAs)-producing bacterium Christensenella minuta, and secondary bile acids (SBAs)-producing bacterium Clostridium leptum. In the UC intervention group, the SCFA-producing bacterium Bacteroides stercoris, IBD-related bacterium Ruminococcus gnavus, Enterococcus faecalis, and the conditional pathogen Bacteroides caccae, were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.}, }
@article {pmid35236743, year = {2022}, author = {Renga, G and Nunzi, E and Pariano, M and Puccetti, M and Bellet, MM and Pieraccini, G and D'Onofrio, F and Santarelli, I and Stincardini, C and Aversa, F and Riuzzi, F and Antognelli, C and Gargaro, M and Bereshchenko, O and Ricci, M and Giovagnoli, S and Romani, L and Costantini, C}, title = {Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite.}, journal = {Journal for immunotherapy of cancer}, volume = {10}, number = {3}, pages = {}, doi = {10.1136/jitc-2021-003725}, pmid = {35236743}, issn = {2051-1426}, abstract = {BACKGROUND: Despite the great success, the therapeutic benefits of immune checkpoint inhibitors (ICIs) in cancer immunotherapy are limited by either various resistance mechanisms or ICI-associated toxic effects including gastrointestinal toxicity. Thus, novel therapeutic strategies that provide manageable side effects to existing ICIs would enhance and expand their therapeutic efficacy and application. Due to its proven role in cancer development and immune regulation, gut microbiome has gained increasing expectation as a potential armamentarium to optimize immunotherapy with ICI. However, much has to be learned to fully harness gut microbiome for clinical applicability. Here we have assessed whether microbial metabolites working at the interface between microbes and the host immune system may optimize ICI therapy.
METHODS: To this purpose, we have tested indole-3-carboxaldehyde (3-IAld), a microbial tryptophan catabolite known to contribute to epithelial barrier function and immune homeostasis in the gut via the aryl hydrocarbon receptor (AhR), in different murine models of ICI-induced colitis. Epithelial barrier integrity, inflammation and changes in gut microbiome composition and function were analyzed. AhR, indoleamine 2,3-dioxygenase 1, interleukin (IL)-10 and IL-22 knockout mice were used to investigate the mechanism of 3-IAld activity. The function of the microbiome changes induced by 3-IAld was evaluated on fecal microbiome transplantation (FMT). Finally, murine tumor models were used to assess the effect of 3-IAld treatment on the antitumor activity of ICI.
RESULTS: On administration to mice with ICI-induced colitis, 3-IAld protected mice from intestinal damage via a dual action on both the host and the microbes. Indeed, paralleling the activation of the host AhR/IL-22-dependent pathway, 3-IAld also affected the composition and function of the microbiota such that FMT from 3-IAld-treated mice protected against ICI-induced colitis with the contribution of butyrate-producing bacteria. Importantly, while preventing intestinal damage, 3-IAld did not impair the antitumor activity of ICI.
CONCLUSIONS: This study provides a proof-of-concept demonstration that moving past bacterial phylogeny and focusing on bacterial metabolome may lead to a new class of discrete molecules, and that working at the interface between microbes and the host immune system may optimize ICI therapy.}, }
@article {pmid35230889, year = {2022}, author = {Ghani, R and Mullish, BH and Roberts, LA and Davies, FJ and Marchesi, JR}, title = {The potential utility of fecal (or intestinal) microbiota transplantation in controlling infectious diseases.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2038856}, doi = {10.1080/19490976.2022.2038856}, pmid = {35230889}, issn = {1949-0984}, abstract = {The intestinal microbiota is recognized to play a role in the defense against infection, but conversely also acts as a reservoir for potentially pathogenic organisms. Disruption to the microbiome can increase the risk of invasive infection from these organisms; therefore, strategies to restore the composition of the gut microbiota are a potential strategy of key interest to mitigate this risk. Fecal (or Intestinal) Microbiota Transplantation (FMT/IMT), is the administration of minimally manipulated screened healthy donor stool to an affected recipient, and remains the major 'whole microbiome' therapeutic approach at present. Driven by the marked success of using FMT in the treatment of recurrent Clostridioides difficile infection, the potential use of FMT in treating other infectious diseases is an area of active research. In this review, we discuss key examples of this treatment based on recent findings relating to the interplay between microbiota and infection, and potential further exploitations of FMT/IMT.}, }
@article {pmid35227890, year = {2022}, author = {Luo, H and Cao, G and Luo, C and Tan, D and Vong, CT and Xu, Y and Wang, S and Lu, H and Wang, Y and Jing, W}, title = {Emerging Pharmacotherapy for Inflammatory Bowel Diseases.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106146}, doi = {10.1016/j.phrs.2022.106146}, pmid = {35227890}, issn = {1096-1186}, abstract = {Inflammatory bowel disease (IBD) refers to a gamut of disorders that are characterized by chronic intestinal inflammation, including ulcerative colitis (UC) and Crohn's disease (CD), which often leads to mucosal ulceration and progressive loss of intestinal function. The etiopathogenesis of IBD has not been completely clarified, although multiple factors involving genetic modifications, host immune dysfunction, intestinal dysbiosis and environmental effects have been implicated. Currently, pharmacotherapies including both non-targeted and targeted biological agents are widely used for the clinical treatment of IBD. In addition, novel therapeutic approaches that target the intestinal microorganisms, such as fecal microbiota transplantation, antibiotics, probiotics and microbial metabolite inhibitors, are also under development. However, these treatments are either accompanied by side effects or cannot achieve complete clinical remission when used alone. The efficacy and safety of drugs are currently a clinical challenge. Thus, advanced drug delivery systems are needed for targeted delivery of drugs to the inflammatory sites and avoid absorption by healthy tissues. In this review, we have summarized the latest research on the pathogenesis of IBD and the emerging pharmacotherapies, and discussed potential therapeutic targets for innovative therapies.}, }
@article {pmid34856844, year = {2021}, author = {Delaroque, C and Chervy, M and Gewirtz, AT and Chassaing, B}, title = {Social overcrowding impacts gut microbiota, promoting stress, inflammation, and dysglycemia.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {2000275}, pmid = {34856844}, issn = {1949-0984}, support = {R01 DK083890/DK/NIDDK NIH HHS/United States ; R01 DK099071/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Blood Glucose/metabolism ; Corticosterone/metabolism ; Crowding/*psychology ; Cytokines/metabolism ; Dysbiosis/metabolism/microbiology/psychology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Gastrointestinal Tract/metabolism/microbiology ; Hyperglycemia/microbiology ; Inflammation ; Mice ; Stress, Psychological/*metabolism/*microbiology/psychology/therapy ; }, abstract = {An array of chronic inflammatory diseases, including metabolic diseases such as obesity and diabetes, are thought to be promoted by disturbance of the intestinal microbiota. Such diseases disproportionately impact low-income communities, which are frequently afflicted by chronic stress and increased density housing. Hence, we hypothesized that overcrowded housing might promote stress, microbiota dysbiosis, inflammation, and, consequently, metabolic diseases. We tested this hypothesis in a tractable murine model of social overcrowding (SOC), in which mice were housed at twice normal density. SOC moderately impacted behavior in some widely used assays (Open Field, Elevated Plus Maze and Light/Dark tests) and resulted in a stark increase in corticosterone levels. Such indices of stress were associated with mild chronic gut inflammation, hyperglycemia, elevations in colonic cytokines, and alterations in gut microbiota composition. All of these consequences of SOC were eliminated by broad spectrum antibiotics, while some (inflammation and hyperglycemia) were transmitted by microbiota transplantation from SOC mice to germfree mice housed at normal density. Altogether, these results suggest a central role for intestinal microbiota in driving stress, inflammation, and chronic diseases that are promoted by overcrowded housing.}, }
@article {pmid34516769, year = {2021}, author = {Rizvi, ZA and Dalal, R and Sadhu, S and Kumar, Y and Kumar, S and Gupta, SK and Tripathy, MR and Rathore, DK and Awasthi, A}, title = {High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity.}, journal = {Science advances}, volume = {7}, number = {37}, pages = {eabg5016}, pmid = {34516769}, issn = {2375-2548}, abstract = {High-salt diet (HSD) modulates effector and regulatory T cell functions and promotes tissue inflammation in autoimmune diseases. However, effects of HSD and its association with gut microbiota in tumor immunity remain undefined. Here, we report that HSD induces natural killer (NK) cell–mediated tumor immunity by inhibiting PD-1 expression while enhancing IFNγ and serum hippurate. Salt enhanced tumor immunity when combined with a suboptimal dose of anti-PD1 antibody. While HSD-induced tumor immunity was blunted upon gut microbiota depletion, fecal microbiota transplantation (FMT) from HSD mice restored the tumor immunity associated with NK cell functions. HSD increased the abundance of Bifidobacterium and caused increased gut permeability leading to intratumor localization of Bifidobacterium, which enhanced NK cell functions and tumor regression. Intratumoral injections of Bifidobacterium activated NK cells, which inhibited tumor growth. These results indicate that HSD modulates gut microbiome that induces NK cell–dependent tumor immunity with a potential translational perspective.}, }
@article {pmid34431607, year = {2021}, author = {Klang, E and Barash, Y and Soffer, S and Shachar, E and Lahat, A}, title = {Trends in inflammatory bowel disease treatment in the past two decades-a high-level text mining analysis of PubMed publications.}, journal = {United European gastroenterology journal}, volume = {9}, number = {9}, pages = {1019-1026}, pmid = {34431607}, issn = {2050-6414}, mesh = {Biological Products/therapeutic use ; Complementary Therapies ; Data Mining/*methods ; Diet ; Fecal Microbiota Transplantation ; Humans ; Incidence ; Inflammatory Bowel Diseases/epidemiology/microbiology/*therapy ; Microbiota ; Prevalence ; Probiotics/therapeutic use ; *PubMed ; }, abstract = {AIM: Many therapeutic options for inflammatory bowel disease (IBD) emerged during the last 2 decades, along with the rise in disease prevalence and incidence. We aimed at assessing the published literature on different treatment options in that period. Special attention was attributed to specific medication mechanisms and geographic diversity.
MATERIALS AND METHODS: We have queried PubMed for all available IBD-related entries published during 2000-2020. The following data were extracted for each entry: PubMed unique article ID (PMID), title, publishing journal, abstract text, keywords (if any), and authors' affiliations. Two gastrointestinal specialists decided in consensus on a list of terms to classify entries. The terms belonged to five treatment groups: medical, surgical, dietary, microbiome manipulation, and complementary medicine. The medical and complementary medicine groups were further sub-classified. Annual trends of publications for the years 2000-2020 were plotted for different treatment types. The slopes of publication trends were calculated by fitting regression lines to the annual number of publications.
RESULTS: Overall, 77,505 IBD entries were published between 2000 and 2020. Medical treatment showed the highest number of total publications 21,540/77,505 (27.8%), followed by surgical 7605/77,505 (9.8%), microbiome research 5260/77,505 (6.8%), dietary 4819/77,505 (6.2%), and complementary medicine treatment 762/77,505 (1.0%). Interestingly, since 2012 there is a steep rise in microbiome publications that outnumbered surgery in the last 2 years. Trend analysis of medical treatment showed that biologics had the steepest slope (57.5, p < 0.001), followed by immunomodulators (4.9, p < 0.001), small molecules (3.9, p < 0.001), and 5-ASA (3.8, p < 0.001).
CONCLUSION: According to our high-level publications trend analysis, the past 2 decades certainly deserve the reference as the "biologic era", as publications regarding biological therapy outnumbered all other treatment options. Interestingly, though very popular among patients, complementary medicine was not studied with correlation to its' acceptance among patients.}, }
@article {pmid35209934, year = {2022}, author = {Fan, L and Ren, J and Chen, Y and Wang, Y and Guo, Z and Bu, P and Yang, J and Ma, W and Zhu, B and Zhao, Y and Cai, J}, title = {Effect of fecal microbiota transplantation on primary hypertension and the underlying mechanism of gut microbiome restoration: protocol of a randomized, blinded, placebo-controlled study.}, journal = {Trials}, volume = {23}, number = {1}, pages = {178}, pmid = {35209934}, issn = {1745-6215}, support = {81630014//national natural science foundation of china/ ; BJJWZYJH01201910023029//beijing outstanding young scientist program/ ; }, abstract = {BACKGROUND: Hypertension is currently the leading modifiable cause of global morbidity and mortality, leading to substantial health and financial burdens. Although multiple studies of management models and innovative therapeutic strategies for hypertension have been conducted, there are still gaps in the field, with a poor control rate reflecting a lack of novel, effective, clinically translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between the microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between the gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention for treating hypertension is thus postulated, and fecal microbiota transplantation (FMT) from healthy donors was performed.
METHODS: A multicenter, randomized, placebo-controlled, blinded clinical trial will be performed in 120 grade 1 hypertensive patients for 3 months. All recruited patients will be randomly assigned in a 1:1 ratio to take oral FMT capsules or placebo capsules on day 1, day 7, and day 14 and will be followed up on day 30, day 60, and day 90. The primary outcome is the change in office systolic blood pressure from baseline to day 30. The main secondary outcomes are BP indicators, including changes in systolic and diastolic blood pressure from office and 24-h ambulatory blood pressure monitoring; assessments of ankle-branchial index and pulse wave velocity; profiling of fecal microbial composition and function; profiling of fecal and serum metabolome; changes in levels of blood glucose, blood lipids, and body mass index; and assessment of adverse events as a measure of safety.
DISCUSSION: Expanding upon our previous research on the role of the gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and explores the potential of fecal microbiota transplantation for treating hypertension. The underlying mechanisms, particularly the roles of specific microorganisms or their postbiotics in blood pressure amelioration, will also be investigated via multiple approaches, such as metagenomic sequencing and metabolomic profiling.
TRIAL REGISTRATION: ClinicalTrials.gov NCT04406129 . Registered on May 28, 2020.}, }
@article {pmid35208740, year = {2022}, author = {Di Pilato, V and Morecchiato, F and Rizzato, C and Quaranta, G and Fais, R and Gandolfo, C and Antonelli, A and Cusi, MG and Pistello, M and Rossolini, GM and Sanguinetti, M and Lupetti, A and Masucci, L}, title = {Validation of Two Commercial Multiplex Real-Time PCR Assays for Detection of SARS-CoV-2 in Stool Donors for Fecal Microbiota Transplantation.}, journal = {Microorganisms}, volume = {10}, number = {2}, pages = {}, doi = {10.3390/microorganisms10020284}, pmid = {35208740}, issn = {2076-2607}, abstract = {Recurrent infection by Clostridioides difficile has recently been treated by fecal microbiota transplantation (FMT). As viable SARS-CoV-2 was recovered from stool of asymptomatic individuals, the FMT procedure could be a potential risk of SARS-CoV-2 transmission, thus underlying the need to reliably detect SARS-CoV-2 in stool. Here, we performed a multicentric study to explore performances of two commercially available assays for detection of SARS-CoV-2 RNA in stool of potential FMT donors. In three hospitals, 180 stool samples were spiked with serial 10-fold dilutions of a SARS-CoV-2 inactivated lysate to evaluate the Seegene Allplex™ SARS-CoV-2 (SC2) and SARS-CoV-2/FluA/FluB/RSV (SC2FABR) Assays for the detection of viral RNA in stool of FMT donors. The results revealed that both assays detected down to 2 TCID50/mL with comparable limit of detection values, SC2 showing more consistent target positivity rate than SC2FABR. Beyond high amplification efficiency, correlation between CT values and log concentrations of inactivated viral lysates showed R2 values ranging from 0.88 to 0.90 and from 0.87 to 0.91 for the SC2 and SC2FABR assay, respectively. The present results demonstrate that both methods are highly reproducible, sensitive, and accurate for SARS-CoV-2 RNA detection in stool, suggesting a potential use in FMT-donor screening.}, }
@article {pmid35207328, year = {2022}, author = {Zhang, X and Ishikawa, D and Nomura, K and Fukuda, N and Haraikawa, M and Haga, K and Shibuya, T and Mita, T and Nagahara, A}, title = {Donor Screening Revisions of Fecal Microbiota Transplantation in Patients with Ulcerative Colitis.}, journal = {Journal of clinical medicine}, volume = {11}, number = {4}, pages = {}, doi = {10.3390/jcm11041055}, pmid = {35207328}, issn = {2077-0383}, support = {JP16K09328//KAKENHI/ ; Kyowa Kirin Co., Ltd.,//Kyowa Kirin Co., Ltd.,/ ; Kyowa Hakko Bio Co.,//Kyowa Hakko Bio Co.,/ ; Kirin Holdings Co., Ltd.//Kirin Holdings Co., Ltd./ ; }, abstract = {Fecal microbiota transplantation (FMT) has been recognized as a promising treatment for dysbiosis-related diseases. Since 2014, FMT has been utilized to treat ulcerative colitis (UC) in our clinical studies and has shown efficacy and safety. As donor screening (DS) is the primary step to ensure the safety of FMT, we report our experience with DS and present the screening results to improve the prospective DS criteria and provide references for future studies. The donor candidates were screened according to the DS criteria. The first DS criteria were proposed in June 2014 and revised substantially in May 2018. We further sorted the screening results and costs of laboratory tests. From June 2014 to April 2018, the DS eligibility rate was 50%. The total laboratory testing cost for each candidate was JPY 17,580/USD 160.21. From May 2018 to September 2021, the DS eligibility rate was 25.6%. The total laboratory testing cost for each candidate was JPY 40,740/USD 371.36. The reduction in donor eligibility rates due to more stringent criteria should be considered for cost and safety. Studies must consider the latest updates and make timely modifications in the DS criteria to ensure patient safety.}, }
@article {pmid35203709, year = {2022}, author = {Panther, EJ and Dodd, W and Clark, A and Lucke-Wold, B}, title = {Gastrointestinal Microbiome and Neurologic Injury.}, journal = {Biomedicines}, volume = {10}, number = {2}, pages = {}, doi = {10.3390/biomedicines10020500}, pmid = {35203709}, issn = {2227-9059}, abstract = {Communication between the enteric nervous system (ENS) of the gastrointestinal (GI) tract and the central nervous system (CNS) is vital for maintaining systemic homeostasis. Intrinsic and extrinsic neurological inputs of the gut regulate blood flow, peristalsis, hormone release, and immunological function. The health of the gut microbiome plays a vital role in regulating the overall function and well-being of the individual. Microbes release short-chain fatty acids (SCFAs) that regulate G-protein-coupled receptors to mediate hormone release, neurotransmitter release (i.e., serotonin, dopamine, noradrenaline, γ-aminobutyric acid (GABA), acetylcholine, and histamine), and regulate inflammation and mood. Further gaseous factors (i.e., nitric oxide) are important in regulating inflammation and have a response in injury. Neurologic injuries such as ischemic stroke, spinal cord injury, traumatic brain injury, and hemorrhagic cerebrovascular lesions can all lead to gut dysbiosis. Additionally, unfavorable alterations in the composition of the microbiota may be associated with increased risk for these neurologic injuries due to increased proinflammatory molecules and clotting factors. Interventions such as probiotics, fecal microbiota transplantation, and oral SCFAs have been shown to stabilize and improve the composition of the microbiome. However, the effect this has on neurologic injury prevention and recovery has not been studied extensively. The purpose of this review is to elaborate on the complex relationship between the nervous system and the microbiome and to report how neurologic injury modulates the status of the microbiome. Finally, we will propose various interventions that may be beneficial in the recovery from neurologic injury.}, }
@article {pmid35202891, year = {2022}, author = {Alonso, CD and Maron, G and Kamboj, M and Carpenter, PA and Gurunathan, A and Mullane, K and Dubberke, ER}, title = {American Society for Transplantation and Cellular Therapy Series: #5 - Management of Clostridioides difficile infection in hematopoietic cell transplant recipients.}, journal = {Transplantation and cellular therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtct.2022.02.013}, pmid = {35202891}, issn = {2666-6367}, abstract = {The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy (ASTCT) partnered with its Transplant Infectious Disease Special Interest Group (TID-SIG) to update its 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A completely new approach was taken with the goal of better serving clinical providers by publishing each standalone topic in the infectious disease series as a concise format of frequently asked questions (FAQ), tables and figures.1 Adult and pediatric infectious disease and HCT content experts developed, then answered FAQs, and finalized topics with harmonized recommendations that were made by assigning an A through E strength of recommendation paired with a level of supporting evidence graded I through III. This fifth guideline in the series focuses on Clostridioides difficile infection with FAQs that address the prevalence, incidence, clinical features, colonization versus infection, clinical complications, diagnostic considerations, pharmacological therapies for episodic or recurrent infection, and the roles of prophylactic antibiotics, probiotics, and fecal microbiota transplantation.}, }
@article {pmid35201766, year = {2022}, author = {Lu, X and Jing, Y and Zhang, N and Cao, Y}, title = {Eurotium cristatum, a Probiotic Fungus from Fuzhuan Brick Tea, and Its Polysaccharides Ameliorated DSS-Induced Ulcerative Colitis in Mice by Modulating the Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.1c08301}, pmid = {35201766}, issn = {1520-5118}, abstract = {Eurotium cristatum is a potential probiotic fungus that is used to enhance Fuzhuan tea quality through fermentation and could reduce obesity by modulating gut dysbiosis. This study aimed to investigate the effects and possible mechanisms of killed E. cristatum (KEC) and its polysaccharides (ECP) in ulcerative colitis (UC) relief. KEC and ECP were administered to mice with dextran sulfate sodium-induced UC. The results showed that UC severity, intestinal inflammation, and tight junction protein levels were greatly improved. Furthermore, 16S rRNA sequencing results showed that Escherichia coli, Enterococcus faecium, Clostridium perfringens, Bacteroides caccae, Rothia aeria, and Prevotella melaninogenica were depleted, while Alistipes finegoldii and Bacteroides stercorirosoris were enriched. A fecal microbial transplantation trial confirmed that KEC and ECP ameliorated UC by regulating gut dysbiosis. Thus, this research suggests that KEC and ECP are novel, potent, food-based anti-inflammatory agents that relieve UC by modulating gut dysbiosis.}, }
@article {pmid35199405, year = {2022}, author = {Singh, V and Ahlawat, S and Mohan, H and Gill, SS and Sharma, KK}, title = {Balancing reactive oxygen species generation by rebooting gut microbiota.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jam.15504}, pmid = {35199405}, issn = {1365-2672}, abstract = {Reactive oxygen species (ROS; free radical form O2 •‾ , superoxide radical; OH• , hydroxyl radical; ROO• , peroxyl; RO• , alkoxyl and non-radical form 1 O2 , singlet oxygen; H2 O2 , hydrogen peroxide) are inevitable companions of aerobic life with crucial role in gut health. But, overwhelming production of ROS can cause serious damage to biomolecules. In this review, we have discussed several sources of ROS production that can be beneficial or dangerous to the human gut. Microorganisms, organelles and enzymes play crucial role in ROS generation, where, NOX1 is the main intestinal enzyme, which produce ROS in the intestine epithelial cells. Previous studies have reported that probiotics play significant role in gut homeostasis by checking the ROS generation, maintaining the antioxidant level, immune system and barrier protection. With current knowledge, we have critically analyzed the available literature and presented the outcome in the form of bubble maps to suggest the probiotics that help in controlling the ROS-specific intestinal diseases, such as inflammatory bowel disease (IBD) and colon cancer. Finally, it has been concluded that rebooting of the gut microbiota with probiotics, postbiotics or fecal microbiota transplantation (FMT) can have crucial implications in the structuring of gut communities for the personalized management of the gastrointestinal (GI) diseases.}, }
@article {pmid35196976, year = {2022}, author = {Ahmed, LA and Massri, KFA}, title = {Gut Microbiota Modulation for Therapeutic Management of Various Diseases: A New Perspective Using Stem Cell Therapy.}, journal = {Current molecular pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/1874467215666220222105004}, pmid = {35196976}, issn = {1874-4702}, abstract = {Dysbiosis has been linked to various diseases ranging from cardiovascular, neurologic, gastrointestinal, respiratory, and metabolic illnesses to cancer. Restoring of gut microbiota balance represents an outstanding clinical target for the management of various multidrug-resistant diseases. Preservation of gut microbial diversity and composition could also improve stem cell therapy which has now diverse clinical applications in the field of regenerative medicine. Gut microbiota modulation and stem cell therapy may be considered a highly promising field that could add up towards improvement of different diseases, increasing the outcome and efficacy of each other, through mutual interplay or interaction between both therapies. Importantly, more investigations are required to reveal the cross-talk between microbiota modulation and stem cell therapy to pave the way for the development of new therapies with enhanced therapeutic outcome. This review provides an overview of dysbiosis in various diseases and their management. It also discusses microbiota modulation via antibiotic, probiotics, prebiotics and fecal microbiota transplant, to introduce the concept of dysbiosis correction for the management of various diseases. Furthermore, we demonstrate the beneficial interactions between microbiota modulation and stem cell therapy as a way for the development of new therapies in addition to limitations and future challenges regarding the applications of these therapies.}, }
@article {pmid35196629, year = {2022}, author = {Bi, W and Cai, S and Hang, Z and Lei, T and Wang, D and Wang, L and Du, H}, title = {Transplantation of feces from mice with Alzheimer's disease promoted lung cancer growth.}, journal = {Biochemical and biophysical research communications}, volume = {600}, number = {}, pages = {67-74}, doi = {10.1016/j.bbrc.2022.01.078}, pmid = {35196629}, issn = {1090-2104}, abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurologic disorder that causes the brain to shrink and brain cells to die. Lung cancer is characterized by high morbidity and mortality, late diagnosis and poor prognosis. And there is no specific mechanism to explain the epidemiological correlation between AD and lung cancer.
MATERIALS AND METHODS: Lewis lung cancer cells (LLC) were injected into the left forelimb armpit of APP/PS1 mice to establish a tumor-bearing model. After remodeling the gut microbiota by fecal microbiota transplantation (FMT), the tumor were collected and analyzed for tumor size, Western blotting, and 16S rRNA gene sequencing.
RESULTS: Compared with the control group, the AD FMT group showed larger tumors, while C57 FMT group showed smaller tumors. The former group showed the inhibition of AKT/Bax/Bcl-2 pathway, while the latter showed promotion of Caspase-1/IL-1β and AKT/Bax/Bcl-2 pathway, which induced changes in tumor size. And Prevotella, Prevotella, Mucispirillum and Halomonas in the gut lumen of LLC tumor-bearing mice are increased, and Bacteroides, Coprobacillus, Bifidobacterium, Faecalibacterium and Aggregatiacter are decreased significantly.
CONCLUSION: AD and lung cancer showed a positive correlation in APP expression, which proposed a different view from epidemiology on the correlation between AD and lung cancer.}, }
@article {pmid35195774, year = {2022}, author = {Shi, Q and Dai, L and Zhao, Q and Zhang, X}, title = {A review on the effect of gut microbiota on metabolic diseases.}, journal = {Archives of microbiology}, volume = {204}, number = {3}, pages = {192}, pmid = {35195774}, issn = {1432-072X}, support = {32101368//National Natural Science Foundation of China/ ; 2020JJ5709//Natural Science Foundation of Hunan Province/ ; 2021-50//Science and Technology Plan Project for Natural Resources of Hunan Province/ ; }, abstract = {Human gut microbiota are a huge and complex microbial community, which is recognized to play a significant role in regulating host metabolism. However, the destruction of gut microbiota leads to the pathological response of host, and thus results in a variety of metabolic diseases. This article gives a brief review of research progress on gut microbiota and some main metabolic diseases, including osteoporosis, obesity, type 2 diabetes, non-alcoholic fatty liver, and hypertension, with a specific focus on the effect of gut microbiota on diseases' occurrence and development. In addition, this review article also shows some case studies on the regulation of gut microbiota by new means, such as fecal microbiota transplantation and oral probiotics. Although gut microbiota are considered as a promising novel target for the treatment of metabolic diseases, it is also necessary to encourage further studies to provide more valuable data for guiding the application of gut microbiota on disease therapy in future.}, }
@article {pmid35193638, year = {2022}, author = {Stallmach, A and Grunert, P and Stallhofer, J and Löffler, B and Baier, M and Rödel, J and Kiehntopf, M and Neugebauer, S and Pieper, DH and Junca, H and Tannapfel, A and Merkel, U and Schumacher, U and Breternitz-Gruhne, M and Heller, T and Schauer, A and Hartmann, M and Steube, A}, title = {Transfer of FRozen Encapsulated multi-donor Stool filtrate for active ulcerative Colitis (FRESCO): study protocol for a prospective, multicenter, double-blind, randomized, controlled trial.}, journal = {Trials}, volume = {23}, number = {1}, pages = {173}, pmid = {35193638}, issn = {1745-6215}, support = {01KG1814//Bundesministerium für Bildung und Forschung/ ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with significant morbidity and mortality. Although the precise cause remains unknown, disturbances in the intestinal microbial community have been linked to its pathogenesis. Randomized controlled trials in UC and relapsing Clostridioides difficile infection (CDI) have established fecal microbiota (FM) transfer (FMT) as an effective therapy. In this context, preliminary results indicated that the transfer of sterile fecal microbiota filtrates (<0.2 μm; FMF, FMFT) of donor stool also drives gastrointestinal microbiota changes and eliminates symptoms in CDI patients. However, along with the success of FMT, regulatory agencies issued safety alerts following reports of serious adverse events due to transmission of enteric pathogens through FMT. To reduce this risk, we established an extensive test protocol for our donors and quarantine regulations for the produced capsules, but alternative concepts are desirable.
METHODS: Our project is a randomized, controlled, longitudinal, prospective, three-arm, multicenter, double-blind study to determine the safety and efficacy of repeated long-term, multi-donor FM or FMF transfers compared to placebo using oral, frozen capsules in 174 randomized patients with mild to moderate active UC. The primary outcome will be clinical remission at week 12.
DISCUSSION: This proposal aims to examine (a) the efficacy of encapsulated transfer of FM and FMF as a therapy for mild to moderate UC, (b) the short- and long-term safety of FMT and FMFT in patients with UC, and (c) the microbial and immunologic changes that occur after FMT and FMFT to help understand how and why it affects inflammatory bowel disease.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03843385 . DRKS (Deutsches Register für Klinische Studien) DRKS00020471.}, }
@article {pmid35191819, year = {2022}, author = {Liang, H and Song, H and Zhang, X and Song, G and Wang, Y and Ding, X and Duan, X and Li, L and Sun, T and Kan, Q}, title = {Metformin attenuated sepsis-related liver injury by modulating gut microbiota.}, journal = {Emerging microbes & infections}, volume = {}, number = {}, pages = {1-34}, doi = {10.1080/22221751.2022.2045876}, pmid = {35191819}, issn = {2222-1751}, abstract = {Increased evidence shows that gut microbiota acts as the primary regulator of the liver; however, their role in sepsis-related liver injury (SLI) in the elderly is unclear. This study assessed whether metformin could attenuate SLI by modulating gut microbiota in septic aged rats. Cecal ligation and puncture (CLP) was used to induce SLI in aged rats. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. The composition of gut microbiota was analyzed by 16S rRNA sequencing. Moreover, the liver and colon tissues were analyzed by histopathology, immunofluorescence, immunohistochemistry,and reverse transcription polymerase chain reaction (RT-PCR). Metformin improved liver damage, colon barrier dysfunction in aged SLI rats. Moreover, metformin improved sepsis-induced liver inflammation and damage under the presence of gut microbiota. Importantly, FMT assay showed that rats gavaged with feces from metformin-treated SLI rats displayed fewer-severe liver damage and colon barrier dysfunction than did rats gavaged with feces from SLI rats.The gut microbiota composition among the sham-operated, CLP-operated and metformin-treated SLI rats were different. In particular, the proportion of Klebsiella and Escherichia_Shigella was higher in SLI rats than sham-operated and metformin-treated SLI rats;while metformin could increased the proportion of Bifidobacterium, Muribaculaceae, Parabacteroides_distasonis and Alloprevitella in aged SLI rats. Additionally, Klebsiella and Escherichia_Shigella correlated positively with the inflammatory factors in the liver. Our findings suggest that metformin may improve the liver injury by regulating the gut microbiota and alleviating colon barrier dysfunction in septic aged rats, which may be an effective therapy for SLI.}, }
@article {pmid34879222, year = {2022}, author = {Kim, E and Paik, D and Ramirez, RN and Biggs, DG and Park, Y and Kwon, HK and Choi, GB and Huh, JR}, title = {Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4+ T cells.}, journal = {Immunity}, volume = {55}, number = {1}, pages = {145-158.e7}, pmid = {34879222}, issn = {1097-4180}, support = {R01 MH115037/MH/NIMH NIH HHS/United States ; R01 MH119459/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Autism Spectrum Disorder/*immunology/microbiology ; CD4-Positive T-Lymphocytes/*immunology ; Child ; Chromatin/*metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunization ; Inflammation/*immunology/microbiology ; Interleukin-17/*metabolism ; Intestines/*immunology ; Mice ; Neurodevelopmental Disorders/*immunology/microbiology ; Pregnancy ; Prenatal Exposure Delayed Effects/*immunology/microbiology ; }, abstract = {Children with autism spectrum disorders often display dysregulated immune responses and related gastrointestinal symptoms. However, the underlying mechanisms leading to the development of both phenotypes have not been elucidated. Here, we show that mouse offspring exhibiting autism-like phenotypes due to prenatal exposure to maternal inflammation were more susceptible to developing intestinal inflammation following challenges later in life. In contrast to its prenatal role in neurodevelopmental phenotypes, interleukin-17A (IL-17A) generated immune-primed phenotypes in offspring through changes in the maternal gut microbiota that led to postnatal alterations in the chromatin landscape of naive CD4+ T cells. The transfer of stool samples from pregnant mice with enhanced IL-17A responses into germ-free dams produced immune-primed phenotypes in offspring. Our study provides mechanistic insights into why children exposed to heightened inflammation in the womb might have an increased risk of developing inflammatory diseases in addition to neurodevelopmental disorders.}, }
@article {pmid35188867, year = {2022}, author = {Pieters, W and Hugenholtz, F and Kos, K and Cammeraat, M and Moliej, TC and Kaldenbach, D and Klarenbeek, S and Davids, M and Drost, L and de Konink, C and Delzenne-Goette, E and de Visser, KE and Te Riele, H}, title = {Pro-mutagenic effects of the gut microbiota in a Lynch syndrome mouse model.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2035660}, doi = {10.1080/19490976.2022.2035660}, pmid = {35188867}, issn = {1949-0984}, abstract = {The gut microbiota strongly impacts the development of sporadic colorectal cancer (CRC), but it is largely unknown how the microbiota affects the pathogenesis of mismatch-repair-deficient CRC in the context of Lynch syndrome. In a mouse model for Lynch syndrome, we found a nearly complete loss of intestinal tumor development when animals were transferred from a conventional "open" animal facility to specific-pathogen-free (SPF) conditions. Using 16S sequencing we detected large changes in microbiota composition between the two facilities. Transcriptomic analyses of tumor-free intestinal tissues showed signs of strong intestinal inflammation in conventional mice. Whole exome sequencing of tumors developing in Msh2-Lynch mice revealed a much lower mutational load in the single SPF tumor than in tumors developing in conventional mice, suggesting reduced epithelial proliferation in SPF mice. Fecal microbiota transplantations with conventional feces altered the immune landscape and gut homeostasis, illustrated by increased gut length and elevated epithelial proliferation and migration. This was associated with drastic changes in microbiota composition, in particular increased relative abundances of different mucus-degrading taxa such as Desulfovibrio and Akkermansia, and increased bacterial-epithelial contact. Strikingly, transplantation of conventional microbiota increased microsatellite instability in untransformed intestinal epithelium of Msh2-Lynch mice, indicating that the composition of the microbiota influences the rate of mutagenesis in MSH2-deficient crypts.}, }
@article {pmid35188712, year = {2022}, author = {Wang, Y and Shi, Y and Li, W and Wang, S and Zheng, J and Xu, G and Li, G and Shen, X and Yang, J}, title = {Gut microbiota imbalance mediates intestinal barrier damage in high-altitude exposed mice.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.16409}, pmid = {35188712}, issn = {1742-4658}, abstract = {The environmental conditions in high-altitude areas can induce gastrointestinal disorders and changes in gut microbiota. Gut microbiota is closely related to a variety of gastrointestinal diseases, however, the underlying pathogenic mechanisms are not well-identified. This study aimed to investigate the regulatory effect of high altitude on intestinal dysfunction via gut microbiota disturbance. Forty C57BL/6J mice were divided into four groups, i.e. one plain control group (CON) and three high-altitude exposure groups (HAE) (altitude: 4000 m; oxygen content: 12.7%; 1-, 2- and 4-week exposure). Another set of forty mice was divided into two CON and two HAE subgroups. Antibiotic cocktails were administered to one CON and HAE groups, and autoclaved water to the second CON and HAE groups for 4 weeks, respectively. In the fecal microbiota transplantation experiment, there were four transplantation groups, which received respectively: phosphate-buffered saline for 2 weeks, feces from CON for 2 weeks, feces from HAE-4W for 2 weeks, and HAE-4W for 4 weeks. Hematoxylin-eosin staining, Periodic Acid-Schiff staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and qRT-PCR were applied to detect changes in intestinal cellular structure, morphology, apoptosis, and intestinal inflammatory response. Fecal microbiota was analyzed using 16S rDNA Amplicon Sequencing. A high-altitude environment changed the ecological balance of gut microbiota in mice and caused damage to intestinal structure and mucosal barrier in mice. Interestingly, similar damage, which was inhibited by antibiotic cocktails at high altitude, was observed in mice transplanted with fecal microbiota from HAE. High-altitude environment contributes to dyshomeostasis of gut microbiota, thereby impairing the intestinal mucosal barrier, eventually inducing and exacerbating intestinal damage.}, }
@article {pmid35185934, year = {2022}, author = {Zhong, Y and Cao, J and Ma, Y and Zhang, Y and Liu, J and Wang, H}, title = {Fecal Microbiota Transplantation Donor and Dietary Fiber Intervention Collectively Contribute to Gut Health in a Mouse Model.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {842669}, doi = {10.3389/fimmu.2022.842669}, pmid = {35185934}, issn = {1664-3224}, abstract = {Transforming the gut microbiota has turned into the most intriguing target for interventions in multiple gastrointestinal and non-gastrointestinal disorders. Fecal microbiota transplantation (FMT) is a therapeutic tool that administers feces collected from healthy donors into patients to help replenish the gut microbial balance. Considering the random donor selection, to maintain the optimal microbial ecosystem, post-FMT is critical for therapy outcomes but challenging. Aiming to study the interventions of different diets on recipients' gut microbiota post-FMT that originated from donors with different diets, we performed FMT from domestic vs. wild pigs that are living on low-fiber vs. high-fiber diets into the pseudo-GF mouse, followed with fiber-free (FF) or fiber-rich (FR) diets post-FMT. Different patterns of gut microbiota and metabolites were observed when mice FMT from different donors were paired with different dietary fiber contents. Enrichment of bacteria, including Akkermansia and Parabacteroides, together with alteration of metabolites, including palmitic acid, stearic acid, and nicotinic acid, was noted to improve crypt length and mucus layer in the gut in mice FMT from wild pigs fed an FR diet. The results provide novel insight into the different responses of reconstructed gut microbiota by FMT to dietary fiber. Our study highlighted the importance of post-FMT precise dietary interventions.}, }
@article {pmid35185631, year = {2021}, author = {Puricelli, C and Rolla, R and Gigliotti, L and Boggio, E and Beltrami, E and Dianzani, U and Keller, R}, title = {The Gut-Brain-Immune Axis in Autism Spectrum Disorders: A State-of-Art Report.}, journal = {Frontiers in psychiatry}, volume = {12}, number = {}, pages = {755171}, doi = {10.3389/fpsyt.2021.755171}, pmid = {35185631}, issn = {1664-0640}, abstract = {The interest elicited by the large microbial population colonizing the human gut has ancient origins and has gone through a long evolution during history. However, it is only in the last decades that the introduction of high-throughput technologies has allowed to broaden this research field and to disentangle the numerous implications that gut microbiota has in health and disease. This comprehensive ecosystem, constituted mainly by bacteria but also by fungi, parasites, and viruses, is proven to be involved in several physiological and pathological processes that transcend the intestinal homeostasis and are deeply intertwined with apparently unrelated body systems, such as the immune and the nervous ones. In this regard, a novel speculation is the relationship between the intestinal microbial flora and the pathogenesis of some neurological and neurodevelopmental disorders, including the clinical entities defined under the umbrella term of autism spectrum disorders. The bidirectional interplay has led researchers to coin the term gut-brain-immune system axis, subverting the theory of the brain as an immune-privileged site and underscoring the importance of this reciprocal influence already from fetal life and especially during the pre- and post-natal neurodevelopmental process. This revolutionary theory has also unveiled the possibility to modify the gut microbiota as a way to treat and even to prevent different kinds of pathologies. In this sense, some attempts have been made, ranging from probiotic administration to fecal microbiota transplantation, with promising results that need further elaboration. This state-of-art report will describe the main aspects regarding the human gut microbiome and its specific role in the pathogenesis of autism and its related disorders, with a final discussion on the therapeutic and preventive strategies aiming at creating a healthy intestinal microbial environment, as well as their safety and ethical implications.}, }
@article {pmid35184756, year = {2022}, author = {Islam, J and Tanimizu, M and Shimizu, Y and Goto, Y and Ohtani, N and Sugiyama, K and Tatezaki, E and Sato, M and Makino, E and Shimada, T and Ueda, C and Matsuo, A and Suyama, Y and Sakai, Y and Furukawa, M and Usami, K and Yoneyama, H and Aso, H and Tanaka, H and Nochi, T}, title = {Development of a rational framework for the therapeutic efficacy of fecal microbiota transplantation for calf diarrhea treatment.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {31}, pmid = {35184756}, issn = {2049-2618}, support = {Livestock Promotional Subsidy//Japan Racing Association/ ; 18H03969//Japan Society for the Promotion of Science/ ; 20K15478//Japan Society for the Promotion of Science/ ; Core-to-Core Program//Japan Society for the Promotion of Science/ ; Grant for Joint Research Project//The University of Tokyo/ ; }, abstract = {BACKGROUND: Establishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of the differences in farm management practices, the lack of optimal donors, and recipient selection. In this study, the underlying factors of successful and unsuccessful FMT treatment cases are elucidated, and the potential markers for predicting successful FMT are identified using fecal metagenomics via 16S rRNA gene sequencing, fecal metabolomics via capillary electrophoresis time-of-flight mass spectrometry, and machine learning approaches.
RESULTS: Specifically, 20 FMT treatment cases, in which feces from healthy donors were intrarectally transferred into recipient diarrheal calves, were conducted with a success rate of 70%. Selenomonas was identified as a microorganism genus that showed significant donor-recipient compatibility in successful FMT treatments. A strong positive correlation between the microbiome and metabolome data, which is a prerequisite factor for FMT success, was confirmed by Procrustes analysis in successful FMT (r = 0.7439, P = 0.0001). Additionally, weighted gene correlation network analysis confirmed the positively or negatively correlated pairs of bacterial taxa (family Veillonellaceae) and metabolomic features (i.e., amino acids and short-chain fatty acids) responsible for FMT success. Further analysis aimed at establishing criteria for donor selection identified the genus Sporobacter as a potential biomarker in successful donor selection. Low levels of metabolites, such as glycerol 3-phosphate, dihydroxyacetone phosphate, and isoamylamine, in the donor or recipients prior to FMT, are predicted to facilitate FMT.
CONCLUSIONS: Overall, we provide the first substantial evidence of the factors related to FMT success or failure; these findings could improve the design of future microbial therapeutics for treating diarrhea in calves. Video abstract.}, }
@article {pmid35184054, year = {2022}, author = {Okafuji, H and Iida, N and Kitamura, K and Seishima, J and Wang, Z and Yutani, M and Yoshio, T and Yamashita, T and Sakai, Y and Honda, M and Yamashita, T and Fujinaga, Y and Shinkura, R and Hamaguchi, Y and Mizukoshi, E and Kaneko, S}, title = {Oral Corticosteroids Impair Mucin Production and Alter the Posttransplantation Microbiota in the Gut.}, journal = {Digestion}, volume = {}, number = {}, pages = {1-18}, doi = {10.1159/000522039}, pmid = {35184054}, issn = {1421-9867}, abstract = {INTRODUCTION: Gut microbiota alterations cause inflammation in patients with ulcerative colitis (UC). Fecal microbiota transplantation (FMT) enables manipulating the microbiota's composition, but the mechanisms underlying colonization of the posttransplantation microbiota are poorly understood.
METHODS: In this open-label, nonrandomized study, the FMT efficacy and changes in the gut microbiota were evaluated in 8 UC patients with mild-to-moderately active endoscopic colonic lesions. Compositional changes in the fecal and mucosal microbiotas between donors and recipients were examined via 16S rRNA-based sequencing. To investigate the effects of oral corticosteroids on microbiota colonization, FMT was performed in germ-free prednisolone (PSL)-administered mice to examine the factors determining colonization.
RESULTS: Four UC patients achieved clinical remission (CR) after FMT, and 3 also achieved endoscopic remission. The fecal microbiotas of the CR patients changed similar to those of the donors after FMT. The mucin-coding gene, MUC2, was less expressed in the colons of the PSL-dependent patients than in the PSL-free patients. In the mice, PSL treatment decreased the fecal mucin production and altered the posttransplantation fecal microbiota composition. Adding either exogenous mucin or the mucin secretagogue, rebamipide, partially alleviated the PSL-induced dysbiosis of the gut microbiota. Administering rebamipide with FMT from healthy donors relieved inflammation in mice with Enterococcus faecium-induced colitis.
CONCLUSION: Colonic mucin controlled the gut microbiota composition, and oral corticosteroid treatment modified the gut microbiota partly by reducing the colonic mucin.}, }
@article {pmid34907387, year = {2021}, author = {O'Leary, K}, title = {FMT for patients with cancer.}, journal = {Nature medicine}, volume = {27}, number = {12}, pages = {2057}, doi = {10.1038/s41591-021-01611-3}, pmid = {34907387}, issn = {1546-170X}, mesh = {*Fecal Microbiota Transplantation ; Humans ; Melanoma/*therapy ; Treatment Outcome ; }, }
@article {pmid35180124, year = {2022}, author = {Hang, Z and Cai, S and Lei, T and Zhang, X and Xiao, Z and Wang, D and Li, Y and Bi, W and Yang, Y and Deng, S and Wang, L and Li, Q and Du, H}, title = {Transfer of Tumor-Bearing Mice Intestinal Flora Can Ameliorate Cognition in Alzheimer's Disease Mice.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {}, number = {}, pages = {}, doi = {10.3233/JAD-215495}, pmid = {35180124}, issn = {1875-8908}, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) is a potential treatment approach for many diseases. Alzheimer's disease (AD) and cancer have been proven to have a specific antagonistic relationship to FMT.
OBJECTIVE: This article aims to explore whether intestinal flora transplantation from cancer individuals can ameliorate cognitive impairment.
METHODS: Morris water maze and object recognition tests were performed to assess cognitive function after the fecal flora from tumor-bearing and WT mice were transplanted into AD mice by gavage. The effect of flora transplantation on AD was analyzed by thioflavin T staining, western blot, and 16S RNA sequencing.
RESULTS: AD mice with FMT significantly improved short-term memory level and cognitive ability compared with Tg + NaCl group. Inflammatory factors in the plasma were regulated, and Aβ plaques burden in the hippocampus and cortex were decreased. FMT in the tumor-bearing group showed a higher significant amelioration in symptoms compared to the healthy group. 16S RNA sequencing revealed that FMT treatments could reverse the increased Firmicutes and Prevotella and the decreased Bacteroidetes, Bacteroides, and Sutterella in AD mice. AD mice transplanted with tumor-bearing mice feces additionally increased the density of Oscillospira, Odoribacter, and AF12. Furthermore, the predicted functional analyses showed that the metabolism of inorganic and organic salts in the intestinal flora of AD mice was also reversed by FMT.
CONCLUSION: Intestinal flora transplantation from tumor-bearing mice can ameliorate the cognitive impairment of AD mice.}, }
@article {pmid35179760, year = {2022}, author = {Martinelli, V and Albanese, M and Altieri, M and Annovazzi, P and Arabi, S and Bucello, S and Caleri, F and Cerqua, R and Costanzi, C and Cottone, S and Dalla Costa, G and Direnzo, V and Fantozzi, R and Favaretto, A and Lorefice, L and Montini, F and Noce, A and Plewnia, K and Repice, AM and Sacco, R and Vecchio, D}, title = {Gut-oriented interventions in patients with multiple sclerosis: fact or fiction?.}, journal = {European review for medical and pharmacological sciences}, volume = {26}, number = {3}, pages = {935-946}, doi = {10.26355/eurrev_202202_28003}, pmid = {35179760}, issn = {2284-0729}, abstract = {OBJECTIVE: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS.
PATIENTS AND METHODS: We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing).
RESULTS: There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS.
CONCLUSIONS: Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.}, }
@article {pmid35176320, year = {2022}, author = {Fang, S and Wang, T and Li, Y and Xue, H and Zou, J and Cai, J and Shi, R and Wu, J and Ma, Y}, title = {Gardenia jasminoides Ellis polysaccharide ameliorates cholestatic liver injury by alleviating gut microbiota dysbiosis and inhibiting the TLR4/NF-κB signaling pathway.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ijbiomac.2022.02.056}, pmid = {35176320}, issn = {1879-0003}, abstract = {Gardenia jasminoides Ellis is a well-known herbal medicine. In this study, the effect of G. jasminoides Ellis polysaccharide (GPS) on liver injury in an alpha-naphthylisothiocyanate (ANIT)-induced cholestatic mouse model and the associated molecular mechanisms were investigated. GPS administration dose-dependently ameliorated impaired hepatic function, including a 2-7-fold decrease in aminotransferase levels, ameliorating tissue damage, upregulating the expression of farnesoid X receptor (FXR) and pregnane X receptor (PXR) and their downstream efflux transporters, and decreasing the levels of 12 bile acids (BAs), in cholestatic mice. Furthermore, GPS ameliorated gut microbiota dysbiosis, improved intestinal barrier function, and reduced serum and hepatic lipopolysaccharide levels 1.5-fold. GPS also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling, decreased the expression of inflammatory factor genes, and ameliorated hepatic inflammation. Notably, fecal microbiota transplantation from GPS-fed mice also increased the hepatic expression of FXR, PXR, and efflux transporters; decreased the levels of 12 BAs; restored intestinal barrier function; and decreased hepatic inflammation mediated by the TLR4/NF-κB pathway. In conclusion, GPS has a protective effect against cholestatic liver injury through modulation of gut microbiota and inhibition of the TLR4/NF-κB pathway. Regulating gut microbiota using herbal medicine polysaccharides may hold unique therapeutic promise for cholestatic liver diseases.}, }
@article {pmid35176247, year = {2022}, author = {Mayneris-Perxachs, J and Castells-Nobau, A and Arnoriaga-Rodríguez, M and Garre-Olmo, J and Puig, J and Ramos, R and Martínez-Hernández, F and Burokas, A and Coll, C and Moreno-Navarrete, JM and Zapata-Tona, C and Pedraza, S and Pérez-Brocal, V and Ramió-Torrentà, L and Ricart, W and Moya, A and Martínez-García, M and Maldonado, R and Fernández-Real, JM}, title = {Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2022.01.013}, pmid = {35176247}, issn = {1934-6069}, abstract = {Growing evidence implicates the gut microbiome in cognition. Viruses, the most abundant life entities on the planet, are a commonly overlooked component of the gut virome, dominated by the Caudovirales and Microviridae bacteriophages. Here, we show in a discovery (n = 114) and a validation cohort (n = 942) that subjects with increased Caudovirales and Siphoviridae levels in the gut microbiome had better performance in executive processes and verbal memory. Conversely, increased Microviridae levels were linked to a greater impairment in executive abilities. Microbiota transplantation from human donors with increased specific Caudovirales (>90% from the Siphoviridae family) levels led to increased scores in the novel object recognition test in mice and up-regulated memory-promoting immediate early genes in the prefrontal cortex. Supplementation of the Drosophila diet with the 936 group of lactococcal Siphoviridae bacteriophages resulted in increased memory scores and upregulation of memory-involved brain genes. Thus, bacteriophages warrant consideration as novel actors in the microbiome-brain axis.}, }
@article {pmid35026167, year = {2022}, author = {Inglis, D and Quraishi, MN and Green, C and Iqbal, T}, title = {The growth of faecal microbiota transplantation in the UK: time for a registry?.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {7}, number = {2}, pages = {112-114}, doi = {10.1016/S2468-1253(21)00436-2}, pmid = {35026167}, issn = {2468-1253}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous/therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; *Registries ; State Medicine ; United Kingdom ; }, }
@article {pmid34838016, year = {2021}, author = {He, J and He, X and Ma, Y and Yang, L and Fang, H and Shang, S and Xia, H and Lian, G and Tang, H and Wang, Q and Wang, J and Lin, Z and Wen, J and Liu, Y and Zhai, C and Wang, W and Jiang, X and Xuan, J and Liu, M and Lu, S and Li, X and Wang, H and Ouyang, C and Cao, M and Lin, A and Zhang, B and Wu, D and Chen, Y and Xiao, C}, title = {A comprehensive approach to stool donor screening for faecal microbiota transplantation in China.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {216}, pmid = {34838016}, issn = {1475-2859}, support = {81730003//national natural science foundation of china/ ; 82004433//national natural science foundation of china/ ; 2017ZX09304021//national major science and technology projects of china/ ; 16CZX064//national office for philosophy and social sciences/ ; }, mesh = {Adolescent ; Adult ; China ; Clostridium Infections/therapy ; Computational Biology/methods ; Donor Selection/*methods ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Male ; Metagenomics/*methods ; Retrospective Studies ; *Tissue Donors ; Young Adult ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China.
RESULTS: The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time.
CONCLUSIONS: DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT.}, }
@article {pmid35172356, year = {2022}, author = {Carlson, TJ and Gonzales-Luna, AJ and Garey, KW}, title = {Fulminant Clostridioides difficile Infection: A Review of Treatment Options for a Life-Threatening Infection.}, journal = {Seminars in respiratory and critical care medicine}, volume = {43}, number = {1}, pages = {28-38}, doi = {10.1055/s-0041-1740973}, pmid = {35172356}, issn = {1098-9048}, abstract = {Fulminant Clostridioides difficile infection (FCDI) encompasses 3 to 5% of all CDI cases with associated mortality rates between 30 and 40%. Major treatment modalities include surgery and medical management with antibiotic and nonantibiotic therapies. However, identification of patients with CDI that will progress to FCDI is difficult and makes it challenging to direct medical management and identify those who may benefit from surgery. Furthermore, since it is difficult to study such a critically ill population, data investigating treatment options are limited. Surgical management with diverting loop ileostomy (LI) instead of a total abdominal colectomy (TAC) with end ileostomy has several appealing advantages, and studies have not consistently demonstrated a clinical benefit with this less-invasive strategy, so both LI and TAC remain acceptable surgical options. Successful medical management of FCDI is complicated by pharmacokinetic changes that occur in critically ill patients, and there is an absence of high-quality studies that included patients with FCDI. Recommendations accordingly include a combination of antibiotics administered via multiple routes to ensure adequate drug concentrations in the colon: intravenous metronidazole, high-dose oral vancomycin, and rectal vancomycin. Although fidaxomicin is now recommended as first-line therapy for non-FCDI, there are limited clinical data to support its use in FCDI. Several nonantibiotic therapies, including fecal microbiota transplantation and intravenous immunoglobulin, have shown success as adjunctive therapies, but they are unlikely to be effective alone. In this review, we aim to summarize diagnosis and treatment options for FCDI.}, }
@article {pmid35166124, year = {2022}, author = {Ben Fradj, S and Nedelec, E and Salvi, J and Fouesnard, M and Huillet, M and Pallot, G and Cansell, C and Sanchez, C and Philippe, C and Gigot, V and Lemoine, A and Trompier, D and Henry, T and Petrilli, V and Py, B and Guillou, H and Loiseau, N and Ellero-Simatos, S and Nahon, JL and Rovère, C and Grober, J and Boudry, G and Douard, V and Benani, A}, title = {Evidence for constitutive microbiota-dependent short-term control of food intake in mice: Is there a link with inflammation, oxidative stress, endotoxemia, and Glp-1?.}, journal = {Antioxidants & redox signaling}, volume = {}, number = {}, pages = {}, doi = {10.1089/ars.2021.0095}, pmid = {35166124}, issn = {1557-7716}, abstract = {AIMS: Although prebiotics, probiotics, and fecal transplantation can alter the sensation of hunger and/or feeding behavior, the role of the constitutive gut microbiota in the short-term regulation of food intake during normal physiology is still unclear.
RESULTS: An antibiotic-induced microbiota depletion study was designed to compare feeding behavior in conventional and microbiota-depleted mice. Tissues were sampled to characterize the time profile of microbiota-derived signals in mice during consumption of either standard or high-fat food for 1 hour. Pharmacological and genetic tools were used to evaluate the contribution of postprandial endotoxemia and inflammatory responses in the short-term regulation of food intake. We observed constitutive microbial and macronutrient-dependent control of food intake at the time scale of a meal, i.e., within 1 hour of food introduction. Specifically, microbiota depletion increased food intake and the microbiota-derived anorectic effect became significant during the consumption of high-fat but not standard food. This anorectic effect correlated with a specific postprandial microbial metabolic signature and did not require postprandial endotoxemia or an NLRP3 (NOD-, LRR- and Pyrin domain-containing protein 3)-inflammasome mediated inflammatory response. Innovation and Conclusion: These findings show that the gut microbiota controls host appetite at the time scale of a meal under normal physiology. Interestingly, a microbiota-derived anorectic effect develops specifically with a high-fat meal, indicating that gut microbiota activity is involved in the satietogenic properties of foods.}, }
@article {pmid35163286, year = {2022}, author = {Alharthi, A and Alhazmi, S and Alburae, N and Bahieldin, A}, title = {The Human Gut Microbiome as a Potential Factor in Autism Spectrum Disorder.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, doi = {10.3390/ijms23031363}, pmid = {35163286}, issn = {1422-0067}, abstract = {The high prevalence of gastrointestinal (GI) disorders among autism spectrum disorder (ASD) patients has prompted scientists to look into the gut microbiota as a putative trigger in ASD pathogenesis. Thus, many studies have linked the gut microbial dysbiosis that is frequently observed in ASD patients with the modulation of brain function and social behavior, but little is known about this connection and its contribution to the etiology of ASD. This present review highlights the potential role of the microbiota-gut-brain axis in autism. In particular, it focuses on how gut microbiota dysbiosis may impact gut permeability, immune function, and the microbial metabolites in autistic people. We further discuss recent findings supporting the possible role of the gut microbiome in initiating epigenetic modifications and consider the potential role of this pathway in influencing the severity of ASD. Lastly, we summarize recent updates in microbiota-targeted therapies such as probiotics, prebiotics, dietary supplements, fecal microbiota transplantation, and microbiota transfer therapy. The findings of this paper reveal new insights into possible therapeutic interventions that may be used to reduce and cure ASD-related symptoms. However, well-designed research studies using large sample sizes are still required in this area of study.}, }
@article {pmid35158960, year = {2022}, author = {Bou Zerdan, M and Niforatos, S and Nasr, S and Nasr, D and Ombada, M and John, S and Dutta, D and Lim, SH}, title = {Fecal Microbiota Transplant for Hematologic and Oncologic Diseases: Principle and Practice.}, journal = {Cancers}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/cancers14030691}, pmid = {35158960}, issn = {2072-6694}, abstract = {Understanding of the importance of the normal intestinal microbial community in regulating microbial homeostasis, host metabolism, adaptive immune responses, and gut barrier functions has opened up the possibility of manipulating the microbial composition to modulate the activity of various intestinal and systemic diseases using fecal microbiota transplant (FMT). It is therefore not surprising that use of FMT, especially for treating relapsed/refractory Clostridioides difficile infections (CDI), has increased over the last decade. Due to the complexity associated with and treatment for these diseases, patients with hematologic and oncologic diseases are particularly susceptible to complications related to altered intestinal microbial composition. Therefore, they are an ideal population for exploring FMT as a therapeutic approach. However, there are inherent factors presenting as obstacles for the use of FMT in these patients. In this review paper, we discussed the principles and biologic effects of FMT, examined the factors rendering patients with hematologic and oncologic conditions to increased risks for relapsed/refractory CDI, explored ongoing FMT studies, and proposed novel uses for FMT in these groups of patients. Finally, we also addressed the challenges of applying FMT to these groups of patients and proposed ways to overcome these challenges.}, }
@article {pmid35158238, year = {2022}, author = {Zhou, Y and Feng, Y and Cen, R and Hou, X and Yu, H and Sun, J and Zhou, L and Ji, Q and Zhao, L and Wang, Y and Li, Q}, title = {San-Wu-Huang-Qin decoction attenuates tumorigenesis and mucosal barrier impairment in the AOM/DSS model by targeting gut microbiome.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {98}, number = {}, pages = {153966}, doi = {10.1016/j.phymed.2022.153966}, pmid = {35158238}, issn = {1618-095X}, abstract = {BACKGROUND: A classic herbal formula San-Wu-Huang-Qin (SWHQ) decoction has been widely used in clinical practices to prevent and treat colorectal cancer (CRC) for years, but its anti-tumorigenic properties and the underlying mechanisms remain undetermined.
PURPOSE: The present study used a CRC mouse model to clarify whether and how SWHQ suppresses tumorigenesis.
METHODS: Different doses of SWHQ were gavaged to the AOM/DSS model mice to examine its anti-tumor efficacy in comparison with the positive control drug Aspirin. The underlying microbiota-driven anti-tumor action of SWHQ was proven with bacterial manipulations by fecal microbial transplantation (FMT) in vivo and anaerobic culturing in vitro.
RESULTS: SWHQ decoction dose-dependently reduced colonic tumor numbers/loads of AOM/DSS models and suppressed their disease activity index scores. SWHQ also recovered epithelial MUC2 secretion and colonic tight junction protein (ZO-1 and claudin1) expression in the mouse model. Such inhibitory impact on tumorigenesis and mucosal barrier impairment was found to be associated with modulation of gut dysbiosis, particularly for suppressing lipopolysaccharide (LPS) producers. The FMT experiment confirmed the substantial contribution of SWHQ-reshaped microbiota to anti-tumor function and mucosal barrier protection. Moreover, LPS-activated TLR4/NF-κB signaling and its downstream pro-inflammatory factors were significantly suppressed in the colon of SWHQ-treated models and SWHQ-reshaped microbiota recipients.
CONCLUSIONS: We demonstrated that the SWHQ effectively inhibited tumorigenesis and protect mucosal barrier in CRC at least partially by targeting gut microbiota. This study provides scientific basis for the clinical usage of SWHQ in CRC intervention and prevention.}, }
@article {pmid35156893, year = {2022}, author = {Mazzawi, T and Hausken, T and El-Salhy, M}, title = {Changes in colonic enteroendocrine cells of patients with irritable bowel syndrome following fecal microbiota transplantation.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/00365521.2022.2036809}, pmid = {35156893}, issn = {1502-7708}, abstract = {OBJECTIVES: The aim was to investigate the effect of fecal microbiota transplantation (FMT) on colonic enteroendocrine cells densities in patients with irritable bowel syndrome (IBS).
MATERIALS AND METHODS: This study is connected to the REFIT study, a double-blinded placebo-controlled trial to investigate using FMT for IBS treatment. Eighty-three subjects received either donor-FMT or placebo FMT (own feces) by colonoscope to cecum. Biopsies were obtained from sigmoid colon. Ten responders and ten non-responders consented to new biopsy one-year after FMT. Sixteen patients received donor-FMT and four received placebo FMT. Biopsies were immunostained for all of the colonic enteroendocrine cells and were quantified using computerized image analysis.Allocation sequence was revealed after obtaining re-biopsies and cells quantification.
RESULTS: Scores for IBS-SSS (mean ± SEM) of responders (eight of 10 patients who received donor FMT) and non-responders changed from baseline to one year after FMT (297 ± 11 and 81 ± 16, p < .0001, and 270 ± 17 and 291 ± 16, p = .15, respectively). Using paired t-test to compare enteroendocrine cells densities one-year after FMT to baseline showed significant increase only in somatostatin immunoreactive cells density in the total IBS responders group (p = .023) and who received donor-FMT (p = .038). The densities of peptide YY and enteroglucagon immunoreactive cells increased significantly (p = .04 and .035, respectively) in donor-FMT recipients. No significant changes were noted in placebo FMT or nonresponders subgroups.
CONCLUSION: This study shows that colonic enteroendocrine cells densities significantly change in responders group that received donor-FMT. The mechanisms for the cross talks between gut microbiota and colonic enteroendocrine cells remain to be investigated.}, }
@article {pmid35156318, year = {2022}, author = {Liu, B and Chen, X and Zhou, L and Li, J and Wang, D and Yang, W and Wu, H and Yao, J and Yang, G and Wang, C and Feng, J and Jiang, T}, title = {The gut microbiota of bats confers tolerance to influenza virus (H1N1) infection in mice.}, journal = {Transboundary and emerging diseases}, volume = {}, number = {}, pages = {}, doi = {10.1111/tbed.14478}, pmid = {35156318}, issn = {1865-1682}, abstract = {Pathogens from wild animals cause approximately 60 percent of emerging infectious diseases (EIDs). Studies on the immune systems of natural hosts are helpful for preventing the spread of EIDs. Bats are natural hosts for many emerging infectious pathogens and have a unique immune system that often coexists with pathogens without infection. Previous studies have shown that some genes and proteins may help bats fight virus infection, but little is known about the function of the bat gut microbiome on immunity. Here, we transplanted gut microbiota from wild bats (Great Himalayan Leaf-nosed bats, Hipposideros armiger) into antibiotic-treated mice, and found that the gut microbiota from bats regulated the immune system faster than mice after antibiotic treatment. Moreover, we infected mice with H1N1, and found that the gut microbiota of bats could effectively protect mice, leading to decreased inflammatory response and increased survival rate. Finally, metabolomics analysis showed that the gut microbiota of bats produced more flavonoid and isoflavones. Our results demonstrate that the quick-start innate immune response endowed by bat gut microbiota and the regulatory and antiviral effects of gut microbiota metabolites successfully ensured mouse survival after viral challenge. To our knowledge, our study was the first to use fecal microbiota transplantation (FMT) to transplant the gut microbiota of bats into mice, and the first to provide evidence that the gut microbiota of bats confers tolerance to viral infections. This article is protected by copyright. All rights reserved.}, }
@article {pmid35155283, year = {2022}, author = {Zhou, A and Yuan, Y and Yang, M and Huang, Y and Li, X and Li, S and Yang, S and Tang, B}, title = {Crosstalk Between the Gut Microbiota and Epithelial Cells Under Physiological and Infectious Conditions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {832672}, doi = {10.3389/fcimb.2022.832672}, pmid = {35155283}, issn = {2235-2988}, abstract = {The gastrointestinal tract (GIT) is considered the largest immunological organ, with a diverse gut microbiota, that contributes to combatting pathogens and maintaining human health. Under physiological conditions, the crosstalk between gut microbiota and intestinal epithelial cells (IECs) plays a crucial role in GIT homeostasis. Gut microbiota and derived metabolites can compromise gut barrier integrity by activating some signaling pathways in IECs. Conversely, IECs can separate the gut microbiota from the host immune cells to avoid an excessive immune response and regulate the composition of the gut microbiota by providing an alternative energy source and releasing some molecules, such as hormones and mucus. Infections by various pathogens, such as bacteria, viruses, and parasites, can disturb the diversity of the gut microbiota and influence the structure and metabolism of IECs. However, the interaction between gut microbiota and IECs during infection is still not clear. In this review, we will focus on the existing evidence to elucidate the crosstalk between gut microbiota and IECs during infection and discuss some potential therapeutic methods, including probiotics, fecal microbiota transplantation (FMT), and dietary fiber. Understanding the role of crosstalk during infection may help us to establish novel strategies for prevention and treatment in patients with infectious diseases, such as C. difficile infection, HIV, and COVID-19.}, }
@article {pmid35151859, year = {2022}, author = {Xu, X and Zhan, G and Chen, R and Wang, D and Guan, S and Xu, H}, title = {Gut microbiota and its role in stress-induced hyperalgesia: gender-specific responses linked to different changes in serum metabolites.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {106129}, doi = {10.1016/j.phrs.2022.106129}, pmid = {35151859}, issn = {1096-1186}, abstract = {Long-term stress causes hyperalgesia; and there are gender differences in the mechanism of pain in male and female individuals. The role of gut microbiota in pain has also been verified. However, whether gut microbiota plays a role in hyperalgesia caused by chronic restraint stress (CRS) with gender differences has not been explored. This study investigated the role of gut microbiota in CRS-induced hyperalgesia gender-specifically through 16S ribosomal RNA (16S rRNA) gene sequencing and untargeted metabolomic analysis using liquid chromatography-mass spectrometry (LC-MS). The study found that both male and female mice experienced hyperalgesia after CRS and antibiotic treatment. 16S rRNA gene sequencing reveals gender differences in the fecal microbiota induced by CRS. The pain threshold decreased after transplanting the fecal microbiota from the male and female CRS group to the corresponding pseudo-germ-free mice. In addition, this study detected gender differences in the host gut microbiota and serum metabolism induced by fecal microbiota transplantation (FMT). Specifically, the different serum metabolites between the pseudo-germ-free mice receiving FMT from the CRS group and those from the control group were mainly involved in bile secretion and steroid hormone biosynthesis for male mice, and in taurine and hypotaurine metabolism and tryptophan metabolism for female mice. In summary, the gut microbiota participates in stress-induced hyperalgesia (SIH) with gender differences by influencing the host's gut microbiota composition and serum metabolism. Therefore, our findings provided insights into developing novel gut microbiota-associated drugs for the management of gender-specific SIH.}, }
@article {pmid35151796, year = {2022}, author = {Chang, L and Wei, Y and Hashimoto, K}, title = {Brain Research Bulletin: Special Issue: Brain-body communication in health and diseases, Brain-gut-microbiota axis in depression: A historical overview and future directions.}, journal = {Brain research bulletin}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.brainresbull.2022.02.004}, pmid = {35151796}, issn = {1873-2747}, abstract = {Depression is the most common mental disorder and a leading cause of disability worldwide. Despite abundant research, the precise mechanisms underlying the pathophysiology of depression remain elusive. Accumulating evidence from preclinical and clinical studies suggests that alterations in the gut microbiota, microbe-derived short-chain fatty acids, D-amino acids and metabolites play a key role in the pathophysiology of depression via the brain-gut-microbiota axis, including the neural and immune systems. Notably, the brain-gut-microbiota axis might play a crucial role in susceptibility versus resilience in rodents exposed to stress. Vagotomy is reported to block depression-like phenotypes in rodents after fecal microbiota transplantation of "depression-related" microbiome, suggesting that the vagus nerve influences depression through the brain-gut-microbiota axis. In this article, we review recent findings regarding the brain-gut-microbiota axis in depression and discuss its potential as a therapeutic target for depression.}, }
@article {pmid35084969, year = {2022}, author = {Servick, K}, title = {Alternatives to fecal transplants near approval.}, journal = {Science (New York, N.Y.)}, volume = {375}, number = {6579}, pages = {368-369}, doi = {10.1126/science.ada0539}, pmid = {35084969}, issn = {1095-9203}, mesh = {Capsules ; Clinical Trials, Phase III as Topic ; *Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Drug Approval ; *Fecal Microbiota Transplantation/adverse effects ; Feces/*microbiology ; *Firmicutes ; *Gastrointestinal Microbiome ; Humans ; Microbial Interactions ; *Spores, Bacterial ; United States ; United States Food and Drug Administration ; }, abstract = {[Figure: see text].}, }
@article {pmid34863329, year = {2022}, author = {Fischer, M and Khoruts, A}, title = {Oral lyophilised microbiota for the treatment of ulcerative colitis.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {7}, number = {2}, pages = {108-109}, doi = {10.1016/S2468-1253(21)00433-7}, pmid = {34863329}, issn = {2468-1253}, mesh = {*Colitis, Ulcerative/drug therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid34116209, year = {2021}, author = {Beckmann, L and Künstner, A and Freschi, ML and Huber, G and Stölting, I and Ibrahim, SM and Hirose, M and Freitag, M and Langan, EA and Matschl, U and Galuska, CE and Fuchs, B and Knobloch, JK and Busch, H and Raasch, W}, title = {Telmisartan induces a specific gut microbiota signature which may mediate its antiobesity effect.}, journal = {Pharmacological research}, volume = {170}, number = {}, pages = {105724}, doi = {10.1016/j.phrs.2021.105724}, pmid = {34116209}, issn = {1096-1186}, mesh = {Angiotensin II Type 1 Receptor Blockers/*pharmacology ; Animals ; Anti-Obesity Agents/*pharmacology ; Bacteria/*drug effects/growth & development ; Diet/adverse effects ; Disease Models, Animal ; Dysbiosis ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Mice ; Obesity/*drug therapy/etiology/microbiology/physiopathology ; Rats ; Rats, Sprague-Dawley ; Telmisartan/*pharmacology ; Weight Gain/*drug effects ; }, abstract = {Telmisartan prevents diet-induced obesity (DIO) in rodents. Given that the precise underlying mechanism is not known, we examined whether a gut-related mechanism might be involved. Sprague-Dawley rats received cafeteria diet (CD) for 3 months to develop DIO and were administered either telmisartan (8 mg/kgbw) or vehicle. In addition, pair-fed (PF) rats received CD adjusted to TEL and control rats (CON) only received chow. Stool samples were analysed by 16 S rRNA gene amplicon sequencing. CD-fed rats became obese while TEL, PF and CON rats remained lean. Alpha diversity analyses indicated that bacterial diversity was similar before the study but changed over time. Beta diversity revealed a time-, CD- and telmisartan-dependent effect. The Firmicutes/Bacteroidetes ratio and the abundance of Blautia, Allobaculum and Parasutterella were higher in DIO and PF than in CON, but not in TEL. Enterotype (ET)-like clustering analyses, Kleinberg's hub network scoring and random forest analyses also indicated that telmisartan induced a specific signature of gut microbiota. In response to stool transfer from telmisartan-pre-treated donor to high-fat fed acceptor mice, body weight gain was slightly attenuated. We attribute the anti-obesity action of telmisartan treatment to diet-independent alterations in gut microbiota as the microbiota from telmisartan-treated, CD-fed rats clearly differed from those of DIO and PF rats. ET-like clustering network, random forest classification and the higher stability in bacterial co-occurrence network analyses indicate that there is more than one indicator species for telmisartan's specific signature, which is further strengthened by the fact that we cannot identify a single indicator species.}, }
@article {pmid35145413, year = {2022}, author = {Singh, R and Zogg, H and Ghoshal, UC and Ro, S}, title = {Current Treatment Options and Therapeutic Insights for Gastrointestinal Dysmotility and Functional Gastrointestinal Disorders.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {808195}, doi = {10.3389/fphar.2022.808195}, pmid = {35145413}, issn = {1663-9812}, abstract = {Functional gastrointestinal disorders (FGIDs) have been re-named as disorders of gut-brain interactions. These conditions are not only common in clinical practice, but also in the community. In reference to the Rome IV criteria, the most common FGIDs, include functional dyspepsia (FD) and irritable bowel syndrome (IBS). Additionally, there is substantial overlap of these disorders and other specific gastrointestinal motility disorders, such as gastroparesis. These disorders are heterogeneous and are intertwined with several proposed pathophysiological mechanisms, such as altered gut motility, intestinal barrier dysfunction, gut immune dysfunction, visceral hypersensitivity, altered GI secretion, presence and degree of bile acid malabsorption, microbial dysbiosis, and alterations to the gut-brain axis. The treatment options currently available include lifestyle modifications, dietary and gut microbiota manipulation interventions including fecal microbiota transplantation, prokinetics, antispasmodics, laxatives, and centrally and peripherally acting neuromodulators. However, treatment that targets the pathophysiological mechanisms underlying the symptoms are scanty. Pharmacological agents that are developed based on the cellular and molecular mechanisms underlying pathologies of these disorders might provide the best avenue for future pharmaceutical development. The currently available therapies lack long-term effectiveness and safety for their use to treat motility disorders and FGIDs. Furthermore, the fundamental challenges in treating these disorders should be defined; for instance, 1. Cause and effect cannot be disentangled between symptoms and pathophysiological mechanisms due to current therapies that entail the off-label use of medications to treat symptoms. 2. Despite the knowledge that the microbiota in our gut plays an essential part in maintaining gut health, their exact functions in gut homeostasis are still unclear. What constitutes a healthy microbiome and further, the precise definition of gut microbial dysbiosis is lacking. More comprehensive, large-scale, and longitudinal studies utilizing multi-omics data are needed to dissect the exact contribution of gut microbial alterations in disease pathogenesis. Accordingly, we review the current treatment options, clinical insight on pathophysiology, therapeutic modalities, current challenges, and therapeutic clues for the clinical care and management of functional dyspepsia, gastroparesis, irritable bowel syndrome, functional constipation, and functional diarrhea.}, }
@article {pmid35093183, year = {2022}, author = {Hyun, J and Lee, SK and Cheon, JH and Yong, DE and Koh, H and Kang, YK and Kim, MH and Sohn, Y and Cho, Y and Baek, YJ and Kim, JH and Ahn, JY and Jeong, SJ and Yeom, JS and Choi, JY}, title = {Faecal microbiota transplantation reduces amounts of antibiotic resistance genes in patients with multidrug-resistant organisms.}, journal = {Antimicrobial resistance and infection control}, volume = {11}, number = {1}, pages = {20}, pmid = {35093183}, issn = {2047-2994}, mesh = {Adult ; Aged ; Bacteria/*genetics ; Carbapenem-Resistant Enterobacteriaceae/genetics ; *Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation/*statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Republic of Korea ; Vancomycin-Resistant Enterococci/genetics ; Young Adult ; }, abstract = {BACKGROUND: Multidrug-resistant organisms (MDROs) such as vancomycin-resistant enterococci (VRE) and carbapenemase-producing Enterobacteriaceae (CPE) are associated with prolonged hospitalisation, increased medical costs, and severe infections. Faecal microbiota transplantation (FMT) has emerged as an important strategy for decolonisation. This study aimed to evaluate the genetic response of MDROs to FMT.
METHODS: A single-centre prospective study was conducted on patients infected with VRE, CPE, or VRE/CPE who underwent FMT between May 2018 and April 2019. Genetic response was assessed as the change in the expression of the resistance genes VanA, blaKPC, blaNDM, and blaOXA on days 1, 7, 14, and 28 by real-time reverse-transcription polymerase chain reaction.
RESULTS: Twenty-nine patients received FMT, of which 26 (59.3%) were infected with VRE, 5 (11.1%) with CPE, and 8 (29.6%) with VRE/CPE. The mean duration of MDRO carriage before FMT was 71 days. Seventeen patients (63.0%) used antibiotics within a week of FMT. In a culture-dependent method, the expression of VanA and overall genes significantly decreased (p = 0.011 and p = 0.003 respectively). In a culture-independent method, VanA, blaNDM, and overall gene expression significantly decreased over time after FMT (p = 0.047, p = 0.048, p = 0.002, respectively). Similar results were confirmed following comparison between each time point in both the culture-dependent and -independent methods. Regression analysis did not reveal important factors underlying the genetic response after FMT. No adverse events were observed.
CONCLUSION: FMT in patients infected with MDROs downregulates the expression of resistance genes, especially VanA, and facilitates MDRO decolonisation.}, }
@article {pmid35143877, year = {2022}, author = {Zhang, Y and Fan, Q and Hou, Y and Zhang, X and Yin, Z and Cai, X and Wei, W and Wang, J and He, D and Wang, G and Yuan, Y and Hao, H and Zheng, X}, title = {Bacteroides Species Differentially Modulate Depression-Like Behavior via Gut-Brain Metabolic Signaling.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2022.02.007}, pmid = {35143877}, issn = {1090-2139}, abstract = {Gut microbiome disturbances have been widely implicated in major depressive disorder (MDD), although the identity of causal microbial species and the underlying mechanisms are yet to be fully elucidated. Here we show that Bacteroides species enriched in the gut microbiome from MDD patients differentially impact the susceptibility to depressive behaviors. Transplantation of fecal microbiome from MDD patients into antibiotic-treated mice induced anxiety and despair-like behavior and impaired hippocampal neurogenesis. Colonization of Bacteroides fragilis, Bacteroides uniformis, and, to a lesser extent, Bacteroides caccae, but not Bacteroides ovatus, recapitulated the negative effects of MDD microbiome on behavior and neurogenesis. The varying impacts of Bacteroides species were partially explained by differential alternations of tryptophan pathway metabolites and neurotransmitters along the gut-brain axis. Notably, an intensified depletion of cerebral serotonin concurred with the enhanced susceptibility to depression. Together, these findings identify select Bacteroidetes species that contribute to depression susceptibility in mice by metabolic regulation along the gut-brain axis.}, }
@article {pmid35140882, year = {2022}, author = {Junca, H and Pieper, DH and Medina, E}, title = {The emerging potential of microbiome transplantation on human health interventions.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {615-627}, doi = {10.1016/j.csbj.2022.01.009}, pmid = {35140882}, issn = {2001-0370}, abstract = {The human microbiome has been the subject of intense research over the past few decades, in particular as a promising area for new clinical interventions. The microbiota colonizing the different body surfaces are of benefit for multiple physiological and metabolic processes of the human host and increasing evidence suggests an association between disturbances in the composition and functionality of the microbiota and several pathological conditions. This has provided a rationale for beneficial modulation of the microbiome. One approach being explored for modulating the microbiota in diseased individuals is transferring microbiota or microbiota constituents from healthy donors via microbiome transplantation. The great success of fecal microbiome transplantation for the treatment of Clostridioides difficile infections has encouraged the application of this procedure for the treatment of other diseases such as vaginal disorders via transplantation of vaginal microbiota, or of skin pathologies via the transplantation of skin microbiota. Microbiome modulation could even become a novel strategy for improving the efficacy of cancer therapies. This review discusses the principle, advantages and limitations of microbiome transplantation as well as different clinical contexts where microbiome transplantation has been applied.}, }
@article {pmid35021112, year = {2022}, author = {Salavati Schmitz, S}, title = {Observational Study of Small Animal Practitioners' Awareness, Clinical Practice and Experience With Fecal Microbiota Transplantation in Dogs.}, journal = {Topics in companion animal medicine}, volume = {47}, number = {}, pages = {100630}, doi = {10.1016/j.tcam.2022.100630}, pmid = {35021112}, issn = {1946-9837}, abstract = {To assess small animal practitioner's awareness of the relatively novel procedure of fecal microbiota transplantation (FMT) in dogs and their practices, indications, experience and assessment of outcome of this in canine patients. An anonymous online questionnaire was distributed to practitioners in the UK and around the world, assessing demographics of respondents, their selection criteria for donors, their operating procedures and indications when performing FMT in dogs, as well as the observed outcomes. Analysis of results was descriptive. Data based on 155 responses from 13 different countries, 40% from primary care practices and 60% from referral hospitals, were analyzed. The majority of respondents (71%) had never performed FMT. For the remaining, main indications were chronic enteropathy (64%) and parvovirus infection (21%), followed by other types of acute diarrhea (15%). The most common mode of administration was via enema (79%) or endoscopically (55%), using fresh (76%) or frozen (46%) preparations mixed with saline and/or water, while the amount administered was extremely variable. Median storage time of FMT was 90 days (range 1-180 days). 67% of participants routinely administer FMT more than once. Clinical response was mixed to good, with rare adverse events (n = 4). A total of 25 respondents (21.7%) wanted to start using FMT, while 45 (29%) wanted to continue or increase FMT administration for various gastrointestinal conditions. In conclusion, an administration of FMT to dogs is currently rare amongst small animal practitioners, but generally follow current recommendations. Urgent consensus regarding donor selection and FMT application procedures for dogs is required.}, }
@article {pmid35135950, year = {2022}, author = {Sekiguchi, E and Toubai, T and Suto, M and Matsuki, E and Miyata, M and Ishizawa, K}, title = {[Fecal metabolomic profiles in experimental murine bone marrow transplantation].}, journal = {[Rinsho ketsueki] The Japanese journal of clinical hematology}, volume = {63}, number = {1}, pages = {37-44}, doi = {10.11406/rinketsu.63.37}, pmid = {35135950}, issn = {0485-1439}, abstract = {Graft-versus-host disease (GVHD) is a life-threating complication of allogeneic hematopoietic cell transplantation (allo-HCT). Prior studies have shown that gastrointestinal (GI) GVHD is associated with a reduction in intestinal microbiota diversity and a change in microbial metabolites. We conducted fecal metabolome analyses using a murine bone marrow transplantation. From this analysis, 290 metabolites were identified; of these, 18 metabolites were significantly or specifically higher and 12 were significantly or specifically lower in the allogeneic group than in the syngeneic one. Particularly, several metabolites in the choline metabolism and tryptophan metabolism were altered in the allogeneic group. Hierarchical clustering analysis demonstrated that the changed metabolites in the allogeneic group had similar profiles. Conclusively, we suggest that alloimmune responses are related to microbial metabolites in recipients receiving allo-HCT. The relationship between metabolites involved in GI GVHD and the intestinal microbiota and its physiological significance warrant further investigations.}, }
@article {pmid35135881, year = {2022}, author = {Jones, EW and Carlson, JM and Sivak, DA and Ludington, WB}, title = {Stochastic microbiome assembly depends on context.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {7}, pages = {}, doi = {10.1073/pnas.2115877119}, pmid = {35135881}, issn = {1091-6490}, abstract = {Observational studies reveal substantial variability in microbiome composition across individuals. Targeted studies in gnotobiotic animals underscore this variability by showing that some bacterial strains colonize deterministically, while others colonize stochastically. While some of this variability can be explained by external factors like environmental, dietary, and genetic differences between individuals, in this paper we show that for the model organism Drosophila melanogaster, interactions between bacteria can affect the microbiome assembly process, contributing to a baseline level of microbiome variability even among isogenic organisms that are identically reared, housed, and fed. In germ-free flies fed known combinations of bacterial species, we find that some species colonize more frequently than others even when fed at the same high concentration. We develop an ecological technique that infers the presence of interactions between bacterial species based on their colonization odds in different contexts, requiring only presence/absence data from two-species experiments. We use a progressive sequence of probabilistic models, in which the colonization of each bacterial species is treated as an independent stochastic process, to reproduce the empirical distributions of colonization outcomes across experiments. We find that incorporating context-dependent interactions substantially improves the performance of the models. Stochastic, context-dependent microbiome assembly underlies clinical therapies like fecal microbiota transplantation and probiotic administration and should inform the design of synthetic fecal transplants and dosing regimes.}, }
@article {pmid34453966, year = {2021}, author = {Bloom, PP and Tapper, EB and Young, VB and Lok, AS}, title = {Microbiome therapeutics for hepatic encephalopathy.}, journal = {Journal of hepatology}, volume = {75}, number = {6}, pages = {1452-1464}, doi = {10.1016/j.jhep.2021.08.004}, pmid = {34453966}, issn = {1600-0641}, support = {K23 DK117055/DK/NIDDK NIH HHS/United States ; }, mesh = {Fecal Microbiota Transplantation/methods/statistics & numerical data ; Hepatic Encephalopathy/*drug therapy ; Host Microbial Interactions/drug effects ; Humans ; Microbiota/*drug effects ; Prebiotics/administration & dosage ; Probiotics/therapeutic use ; }, abstract = {Hepatic encephalopathy (HE) is a complication of cirrhosis characterised by neuropsychiatric and motor dysfunction. Microbiota-host interactions play an important role in HE pathogenesis. Therapies targeting microbial community composition and function have been explored for the treatment of HE. Prebiotics, probiotics and faecal microbiota transplant (FMT) have been used with the aim of increasing the abundance of potentially beneficial taxa, while antibiotics have been used to decrease the abundance of potentially harmful taxa. Other microbiome therapeutics, including postbiotics and absorbents, have been used to target microbial products. Microbiome-targeted therapies for HE have had some success, notably lactulose and rifaximin, with probiotics and FMT also showing promise. However, there remain several challenges to the effective application of microbiome therapeutics in HE, including the resilience of the microbiome to sustainable change and unpredictable clinical outcomes from microbiota alterations. Future work in this space should focus on rigorous trial design, microbiome therapy selection, and a personalised approach to HE.}, }
@article {pmid35115674, year = {2022}, author = {Kim, ES and Yoon, BH and Lee, SM and Choi, M and Kim, EH and Lee, BW and Kim, SY and Pack, CG and Sung, YH and Baek, IJ and Jung, CH and Kim, TB and Jeong, JY and Ha, CH}, title = {Fecal microbiota transplantation ameliorates atherosclerosis in mice with C1q/TNF-related protein 9 genetic deficiency.}, journal = {Experimental & molecular medicine}, volume = {}, number = {}, pages = {}, pmid = {35115674}, issn = {2092-6413}, support = {2020R1I1A2072110//National Research Foundation of Korea (NRF)/ ; 2021R1A6A1A03040260//National Research Foundation of Korea (NRF)/ ; }, abstract = {Despite the strong influence of the gut microbiota on atherosclerosis, a causal relationship between atherosclerosis pathophysiology and gut microbiota is still unverified. This study was performed to determine the impact of the gut microbiota on the pathogenesis of atherosclerosis caused by genetic deficiency. To elucidate the influence of the gut microbiota on atherosclerosis pathogenesis, an atherosclerosis-prone mouse model (C1q/TNF-related protein 9-knockout (CTRP9-KO) mice) was generated. The gut microbial compositions of CTRP9-KO and WT control mice were compared. Fecal microbiota transplantation (FMT) was performed to confirm the association between gut microbial composition and the progression of atherosclerosis. FMT largely affected the gut microbiota in both CTRP9-KO and WT mice, and all transplanted mice acquired the gut microbiotas of the donor mice. Atherosclerotic lesions in the carotid arteries were decreased in transplanted CTRP9-KO mice compared to CTRP9-KO mice prior to transplantation. Conversely, WT mice transplanted with the gut microbiotas of CTRP9-KO mice showed the opposite effect as that of CTRP9-KO mice transplanted with the gut microbiotas of WT mice. Here, we show that CTRP9 gene deficiency is related to the distribution of the gut microbiota in subjects with atherosclerosis. Transplantation of WT microbiotas into CTRP9-KO mice protected against the progression of atherosclerosis. Conversely, the transplantation of CTRP9-KO microbiotas into WT mice promoted the progression of atherosclerosis. Treating atherosclerosis by restoring gut microbial homeostasis may be an effective therapeutic strategy.}, }
@article {pmid35040733, year = {2022}, author = {Gallo, C and Howardson, BO and Cristoferi, L and Carbone, M and Gershwin, ME and Invernizzi, P}, title = {An update on novel pharmacological agents for primary sclerosing cholangitis.}, journal = {Expert opinion on therapeutic targets}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/14728222.2022.2030707}, pmid = {35040733}, issn = {1744-7631}, abstract = {INTRODUCTION: Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease with heterogeneous phenotypes that may lead to liver transplantation and/or end-stage liver disease. Its multifactorial etiopathogenesis remains uncertain, but gut-liver axis and bile composition and excretion are widely demonstrated to influence the immune-mediated fibrogenic reactive cascade.
AREAS COVERED: Different experimental therapeutic options are under investigation, mainly aiming at modulating bile acids excretion, limiting inflammatory-cascade reactions, and changing intestinal microbiota composition; none of them yet demonstrated to prolong transplant-free survival.This review provides a comprehensive description of the experimental drugs recently tested and/or currently under investigation. A bibliographical search was performed in PubMed, MEDLINE, EMBASE, OVID, and clinicaltrial.gov until July 2021.
EXPERT OPINION: The heterogeneity and poor prevalence of PSC, its uncertain pathophysiology, and the lack of surrogate endpoints are the major challenges in drug discovery. Strategies that synergistically target microbiota, bile acids, and liver fibrosis are needed. In parallel, we must enhance biomarkers discovery to develop surrogate endpoints, as biochemical markers' fluctuations over the time hamper their effectiveness. Magnetic resonance cholangiopancreatography tools that accurately measure bile duct changes represent a potential marker for disease monitoring. A collaboration between academia, research consortia, patient's associations, and industry is required.}, }
@article {pmid35130123, year = {2022}, author = {Zhang, X and Walker, K and Mayne, J and Li, L and Ning, Z and Stintzi, A and Figeys, D}, title = {Evaluating live microbiota biobanking using an ex vivo microbiome assay and metaproteomics.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2035658}, doi = {10.1080/19490976.2022.2035658}, pmid = {35130123}, issn = {1949-0984}, abstract = {Biobanking of live microbiota is becoming indispensable for mechanistic and clinical investigations of drug-microbiome interactions and fecal microbiota transplantation. However, there is a lack of methods to rapidly and systematically evaluate whether the biobanked microbiota maintains their cultivability and functional activity. In this study, we use a rapid ex vivo microbiome assay and metaproteomics to evaluate the cultivability and the functional responses of biobanked microbiota to treatment with a prebiotic (fructo-oligosaccharide, FOS). Our results indicate that the microbiota cultivability and their functional responses to FOS treatment were well maintained by freezing in a deoxygenated glycerol buffer at -80°C for 12 months. We also demonstrate that the fecal microbiota is functionally stable for 48 hours on ice in a deoxygenated glycerol buffer, allowing off-site fecal sample collection and shipping to laboratory for live microbiota biobanking. This study provides a method for rapid evaluation of the cultivability of biobanked live microbiota. Our results show minimal detrimental influences of long-term freezing in deoxygenated glycerol buffer on the cultivability of fecal microbiota.}, }
@article {pmid35127797, year = {2021}, author = {Guo, X and Huang, C and Xu, J and Xu, H and Liu, L and Zhao, H and Wang, J and Huang, W and Peng, W and Chen, Y and Nie, Y and Zhou, Y and Zhou, Y}, title = {Gut Microbiota Is a Potential Biomarker in Inflammatory Bowel Disease.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {818902}, doi = {10.3389/fnut.2021.818902}, pmid = {35127797}, issn = {2296-861X}, abstract = {Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is characterized by relapse and remission alternately. It remains a great challenge to diagnose and assess disease activity during IBD due to the lack of specific markers. While traditional biomarkers from plasma and stool, such as C-reactive protein (CRP), fecal calprotectin (FC), and S100A12, can be used to measure inflammation, they are not specific to IBD and difficult to determine an effective cut-off value. There is consensus that gut microbiota is crucial for intestinal dysbiosis is closely associated with IBD etiopathology and pathogenesis. Multiple studies have documented differences in the composition of gut microbiota between patients with IBD and healthy individuals, particularly regarding microbial diversity and relative abundance of specific bacteria. Patients with IBD have higher levels of Proteobacteria and lower amounts of Bacteroides, Eubacterium, and Faecalibacterium than healthy individuals. This review summarizes the pros and cons of using traditional and microbiota biomarkers to assess disease severity and treatment outcomes and addresses the possibility of using microbiota-focused interventions during IBD treatment. Understanding the role of microbial biomarkers in the assessment of disease activity and treatment outcomes has the potential to change clinical practice and lead to the development of more personalized therapies.}, }
@article {pmid35127122, year = {2022}, author = {Bakker, GJ and Meijnikman, AS and Scheithauer, TP and Davids, M and Aydin, Ö and Boerlage, TCC and de Brauw, LM and van de Laar, AW and Gerdes, VE and Groen, AK and van Raalte, DH and Herrema, H and Nieuwdorp, M}, title = {Fecal microbiota transplantation does not alter bacterial translocation and visceral adipose tissue inflammation in individuals with obesity.}, journal = {Obesity science & practice}, volume = {8}, number = {1}, pages = {56-65}, doi = {10.1002/osp4.545}, pmid = {35127122}, issn = {2055-2238}, abstract = {Aims: Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation (FMT) on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed.
Material and Methods: Eight individuals with clinically severe obesity (body mass index [BMI] >35 kg/m2) and metabolic syndrome received lean donor FMT 4 weeks prior to elective bariatric surgery. The participants were age-, sex-, and BMI-matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro-inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation.
Results: Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro-inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed.
Conclusions: Visceral bacterial DNA content and level of inflammation were not altered upon FMT. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity.}, }
@article {pmid35126320, year = {2021}, author = {Vasilescu, IM and Chifiriuc, MC and Pircalabioru, GG and Filip, R and Bolocan, A and Lazăr, V and Diţu, LM and Bleotu, C}, title = {Gut Dysbiosis and Clostridioides difficile Infection in Neonates and Adults.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {651081}, doi = {10.3389/fmicb.2021.651081}, pmid = {35126320}, issn = {1664-302X}, abstract = {In this review, we focus on gut microbiota profiles in infants and adults colonized (CDC) or infected (CDI) with Clostridioides difficile. After a short update on CDI epidemiology and pathology, we present the gut dysbiosis profiles associated with CDI in adults and infants, as well as the role of dysbiosis in C. difficile spores germination and multiplication. Both molecular and culturomic studies agree on a significant decrease of gut microbiota diversity and resilience in CDI, depletion of Firmicutes, Bacteroidetes, and Actinobacteria phyla and a high abundance of Proteobacteria, associated with low butyrogenic and high lactic acid-bacteria levels. In symptomatic cases, microbiota deviations are associated with high levels of inflammatory markers, such as calprotectin. In infants, colonization with Bifidobacteria that trigger a local anti-inflammatory response and abundance of Ruminococcus, together with lack of receptors for clostridial toxins and immunological factors (e.g., C. difficile toxins neutralizing antibodies) might explain the lack of clinical symptoms. Gut dysbiosis amelioration through administration of "biotics" or non-toxigenic C. difficile preparations and fecal microbiota transplantation proved to be very useful for the management of CDI.}, }
@article {pmid35125827, year = {2022}, author = {Hillestad, EMR and van der Meeren, A and Nagaraja, BH and Bjørsvik, BR and Haleem, N and Benitez-Paez, A and Sanz, Y and Hausken, T and Lied, GA and Lundervold, A and Berentsen, B}, title = {Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome.}, journal = {World journal of gastroenterology}, volume = {28}, number = {4}, pages = {412-431}, doi = {10.3748/wjg.v28.i4.412}, pmid = {35125827}, issn = {2219-2840}, abstract = {Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal symptoms, recently described as a disturbance of the microbiota-gut-brain axis. Despite decades of research, the pathophysiology of this highly heterogeneous disorder remains elusive. However, a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture. Are we getting any closer to understanding IBS' etiology, or are we drowning in unspecific, conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing? In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota, clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation, neuroimaging and methods in microbiota analyses, and current and future challenges with big data analysis in IBS.}, }
@article {pmid35125404, year = {2022}, author = {Linares-García, L and Cárdenas-Barragán, ME and Hernández-Ceballos, W and Pérez-Solano, CS and Morales-Guzmán, AS and Miller, DS and Schmulson, M}, title = {Bacterial and Fungal Gut Dysbiosis and Clostridium difficile in COVID-19: A Review.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001669}, pmid = {35125404}, issn = {1539-2031}, abstract = {BACKGROUND: Gastrointestinal symptoms are common in Coronavirus Disease 2019 (COVID-19), related to infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) of intestinal cells through the angiotensin converting enzyme 2 (ACE2) receptor in the brush border. Also, patients are treated with multiple antibiotics. Therefore, an increase in gut dysbiosis and in the prevalence of Clostridium difficile infection (CDI) is expected in patients with COVID-19.
METHODS: A PubMed search was conducted using the terms "gut microbiota," "gut mycobiota," "dysbiosis" AND "COVID-19"; "Clostridium difficile," "Clostridioides difficile" AND "COVID-19"; "probiotics," "bacteriotherapy AND COVID-19." Only case series, observational and experimental studies were included.
RESULTS: A total of 384 papers were retrieved and 21 fulfilled selection criteria. Later, a new paper was identified, thus 22 papers were reviewed. Main findings: (1) gut bacterial dysbiosis has been found in fecal samples of COVID-19 patients, with enrichment of opportunistic organisms and decrease of beneficial commensals such as Faecalibacterium prausnitizii. Dysbiosis is related to inflammatory markers and illness severity. (2) There is evidence for abnormal gut barrier and bacterial translocation with a negative impact in the lungs. (3) Fungal dysbiosis correlating with pulmonary mycobiota, has also been found. (4) There is controversy in the CDI rates among COVID-19 patients versus controls and pandemic versus prepandemic era. (5) There is no available evidence yet to support bacteriotherapy in COVID-19. (6) Fecal microbiota transplantation (FMT) has been proposed for COVID-19, although there is no evidence to support it. Also, FMT can be safely used during the pandemic for CDI if strict screening protocols for donors and fecal product are implemented.
CONCLUSIONS: In COVID-19 there is bacterial and fungal dysbiosis that correlates with systemic and pulmonary inflammation, and illness severity. Further investigations are warranted to determine the efficacy of bacteriotherapy and FMT for modulating gut dysbiosis in COVID-19.}, }
@article {pmid35124952, year = {2022}, author = {Seth, AK and Jain, P}, title = {Fecal microbiota transplantation for induction of remission, maintenance and rescue in patients with corticosteroid-dependent ulcerative colitis: a long-term follow-up real-world cohort study.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2021.00069}, pmid = {35124952}, issn = {1598-9100}, abstract = {Background/Aims: To study role of fecal microbiota transplantation (FMT) in induction, maintenance, and rescue in patients with corticosteroid-dependent ulcerative colitis (CDUC).
Methods: Patients with active CDUC received 3 fortnightly sessions of colonoscopic induction FMT (iFMT) in addition to standard of care. In patients who achieved clinical remission (CR) or response, prednisolone was tapered from week 4 and azathioprine from week 12. Responders were advised maintenance FMT (mFMT) every 6 months. Those with relapse were offered rescue FMT (rFMT), and low dose prednisolone was added if there was no improvement in 2 weeks.
Results: All 27 patients enrolled completed iFMT and were followed up for 39 months (range, 9-71 months). The mean Mayo score decreased from 6.4±2.5 at baseline to 2.6±3.7 at week 4, 2.6±3.4 at week 12, and 2.8±3.8 at week 24 (P<0.05). Corticosteroid-free CR and clinical response at week 12 were seen in 13 patients (48%) and 1 patient (3.7%), respectively. Corticosteroid and azathioprine-free CR at week 24 was seen in 13 patients (48%) and in them histological response was seen in 2 patients (15.2%) at week 4, 5 patients (38.4%) at week 12, and 10 patients (76.9%) at week 24. First relapse was seen in 10 of 13 responders (76.9%) at a median of 14.8 months (range, 6-34 months) after iFMT and was less frequent in patients on mFMT. Relapse was treated successfully with rFMT alone in 4 patients (40%) and rFMT with low dose steroids in 5 patients (50%).
Conclusions: iFMT, mFMT, and rFMT may have a role in treatment of selected patients with CDUC.}, }
@article {pmid35118227, year = {2022}, author = {Song, YN and Yang, DY and Veldhuyzen van Zanten, S and Wong, K and McArthur, E and Song, CZ and Ianiro, G and Cammarota, G and Kelly, C and Fischer, M and Russell, L and Kao, D}, title = {Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile Infection: Systematic Review and Meta-analysis.}, journal = {Journal of the Canadian Association of Gastroenterology}, volume = {5}, number = {1}, pages = {e1-e11}, doi = {10.1093/jcag/gwab023}, pmid = {35118227}, issn = {2515-2092}, abstract = {Background: Severe or fulminant Clostridioides difficile infection (SFCDI) is associated with significant morbidity and mortality. Emerging evidence suggests fecal microbiota transplant (FMT) may be a promising therapy for SFCDI.
Aim: This systematic review determines the safety and efficacy of FMT in medically refractory SFCDI.
Methods: A systematic search of the literature was conducted using PubMed (1965 to 2020), Web of Science (1900 to 20), EMBASE (1974 to 2020), and Cochrane Review (1945 to 2020). Quality appraisal by NIH Study Quality Assessment tools, and data extraction were performed by two teams of independent researchers. The primary outcome was resolution of SFCDI 4 weeks after the final FMT. Pooled resolution rates were calculated using generalized linear mixed models estimates.
Results: Two hundred and forty patients from 10 studies (8 case series, 1 case-control and 1 randomized study) were included with 209 individual patient-level data. FMT resulted in resolution of SFCDI within 4 weeks in 211/240 individuals for a pooled estimate of 88% (95% confidence interval [CI]: 0.83 to 0.91). The mean number of FMT required was 1.6 for severe and 2.0 for fulminant CDI resolution. The pooled proportional estimates for patients requiring CDI-directed antimicrobials after FMT was 50% (95% CI: 0.06 to 0.94) for severe CDI and 67.0% (95% CI: 0.30 to 0.91) for fulminant CDI. Serious adverse event rates were low.
Conclusion: FMT appears effective in treating SFCDI patients with low adverse events, but requires multiple treatments with a significant proportion of patients requiring additional anti-CDI antibiotics to achieve resolution. The optimal route of FMT delivery remains unknown. The presence of pseudomembranous colitis may guide additional FMT or anti-CDI antibiotic treatment.}, }
@article {pmid35116024, year = {2021}, author = {Zhao, ZX and Yuan, X and Cui, YY and Liu, J and Shen, J and Jin, BY and Feng, BC and Zhai, YJ and Zheng, MQ and Kou, GJ and Zhou, RC and Li, LX and Zuo, XL and Li, SY and Li, YQ}, title = {Melatonin Mitigates Oxazolone-Induced Colitis in Microbiota-Dependent Manner.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {783806}, doi = {10.3389/fimmu.2021.783806}, pmid = {35116024}, issn = {1664-3224}, abstract = {Levels of type 2 cytokines are elevated in the blood and intestinal tissues of ulcerative colitis (UC) patients in the active phase; this phenomenon indicates the participation of type 2 immune response in UC progression. The beneficial effects of melatonin in dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis models have been illustrated, but its role in the oxazolone (Oxa)-induced colitis model (driven by type 2 immune response) remains relatively unknown. We investigated the relationship between melatonin concentration and the severity of UC, revealing a significantly negative correlation. Subsequently, we investigated the effects of melatonin in Oxa-induced colitis mice and the potential underlying mechanisms. Administration of melatonin significantly counteracted body weight loss, colon shortening, and neutrophil infiltration in Oxa-induced colitis mice. Melatonin treatment mitigated Oxa-induced colitis by suppressing type 2 immune response. In addition, melatonin attenuated intestinal permeability by enhancing the expression of ZO-1 and occludin in colitis mice. Interestingly, the protective effect of melatonin was abolished when the mice were co-housed, indicating that the regulation of gut microbiota by melatonin was critical in alleviating Oxa-induced colitis. Subsequently, 16S rRNA sequencing was performed to explore the microbiota composition. Decreased richness and diversity of intestinal microbiota at the operational taxonomic unit (OTU) level resulted from melatonin treatment. Melatonin also elevated the abundance of Bifidobacterium, a well-known probiotic, and reduced proportions of several harmful bacterial genera, such as Desulfovibrio, Peptococcaceae, and Lachnospiraceae. Fecal microbiota transplantation (FMT) was used to explore the role of microbiota in the function of melatonin in Oxa-induced colitis. Microbiota transplantation from melatonin-treated mice alleviated Oxa-induced colitis, suggesting that the microbiome participates in the relief of Oxa-induced colitis by melatonin. Our findings demonstrate that melatonin ameliorates Oxa-induced colitis in a microbiota-dependent manner, suggesting the therapeutic potential of melatonin in treating type 2 immunity-associated UC.}, }
@article {pmid35115909, year = {2021}, author = {Yu, X and Fu, X and Wu, X and Tang, W and Xu, L and Hu, L and Xu, C and Zhou, H and Zhou, G and Li, J and Cao, S and Liu, J and Yan, F and Wang, L and Liu, F and Chen, G}, title = {Metformin Alleviates Neuroinflammation Following Intracerebral Hemorrhage in Mice by Regulating Microglia/Macrophage Phenotype in a Gut Microbiota-Dependent Manner.}, journal = {Frontiers in cellular neuroscience}, volume = {15}, number = {}, pages = {789471}, doi = {10.3389/fncel.2021.789471}, pmid = {35115909}, issn = {1662-5102}, abstract = {The gut microbiota plays a key role in regulating intracerebral hemorrhage (ICH)-induced neuroinflammation. The anti-neuroinflammatory effects of metformin (Met) have been reported in many central nervous system (CNS) diseases. However, whether Met regulates neuroinflammation through the gut microbiota in ICH-induced brain injury remains unknown. We found that Met treatment substantially alleviated neurological dysfunction and reduced neuroinflammation by inhibiting pro-inflammatory polarization of microglia/macrophages in mice with ICH. Moreover, Met treatment altered the microbiota composition and improved intestinal barrier function. The expression of lipopolysaccharide-binding protein (LBP), a biomarker of intestinal barrier damage, was also significantly reduced by Met treatment. Neuroinflammation was also potently ameliorated after the transplantation of fecal microbiota from Met-treated ICH mice. The neuroprotective effects of fecal microbiota transplantation (FMT) were similar to those of oral Met treatment. However, suppression of the gut microbiota negated the neuroprotective effects of Met in ICH mice. Therefore, Met is a promising therapeutic agent for neuroinflammation owing to ICH-induced imbalance of the gut microbiota.}, }
@article {pmid35111693, year = {2021}, author = {Xi, S and Wang, Y and Wu, C and Peng, W and Zhu, Y and Hu, W}, title = {Intestinal Epithelial Cell Exosome Launches IL-1β-Mediated Neuron Injury in Sepsis-Associated Encephalopathy.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {783049}, doi = {10.3389/fcimb.2021.783049}, pmid = {35111693}, issn = {2235-2988}, abstract = {Background: Gut-microbiota-brain axis links the relationship between intestinal microbiota and sepsis-associated encephalopathy (SAE). However, the key mediators between them remain unclear.
Methods: Memory test was determined by Water maze. Intestinal flora was measured by 16S RNA sequencing. Neurotransmitter was detected by high-performance liquid chromatography (HPLC). Histopathology was determined by H&E, immunofluorescence (IF), and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining. Flow cytometry was employed to determine the proportion of macrophages.
Results: Fecal microbiota transplantation (FMT) relieved hippocampus impairment of SAE rats by inhibiting inflammation cytokine secretion, the expression of IBA-1 and neurotransmitter disturbance, and cell apoptosis and autophagy, accompanied by the reduced M1 polarization and M1 pro-inflammation factors produced by macrophages in mesenteric lymph nodes (MLNs). Actually, M1 polarization in SAE rats depended on intestinal epithelial cell (IEC)-derived exosome. GW4869-initiated inhibition of exosome secretion notably abolished M1 polarization and the secretion of IL-1β. However, GW4869-mediated improvement of hippocampus impairment was counteracted by the delivery of recombinant interleukin (IL)-1β to hippocampus. Mechanistically, IEC-derived exosome induced the excessive circulating IL-1β produced by CP-R048 macrophages, which subsequently induced damage and apoptosis of hippocampal neurons H19-7 in an autophagy-dependent manner. And reactivation of autophagy facilitates intestinal IL-1β-mediated hippocampal neuron injury.
Conclusion: Collectively, intestinal flora disturbance induced the exosome release of IECs, which subsequently caused M1 polarization in MLNs and the accumulation of circulating IL-1β. Circulating IL-1β promoted the damage and apoptosis of neurons in an autophagy-dependent manner. Possibly, targeting intestinal flora or IEC-derived exosome contributes to the treatment of SAE.}, }
@article {pmid35111551, year = {2021}, author = {Osaki, H and Jodai, Y and Koyama, K and Omori, T and Horiguchi, N and Kamano, T and Funasaka, K and Nagasaka, M and Nakagawa, Y and Shibata, T and Ohmiya, N}, title = {Clinical response and changes in the fecal microbiota and metabolite levels after fecal microbiota transplantation in patients with inflammatory bowel disease and recurrent Clostridioides difficile infection.}, journal = {Fujita medical journal}, volume = {7}, number = {3}, pages = {87-98}, doi = {10.20407/fmj.2020-021}, pmid = {35111551}, issn = {2189-7255}, abstract = {Objectives: We determined the efficacy of fecal microbiota transplantation (FMT) and subsequent changes in fecal microbiota and short-chain fatty acid (SCFA) levels in patients with ulcerative colitis (UC), Crohn's disease (CD), and recurrent Clostridioides difficile infection (rCDI).
Methods: A filtered solution of Japanese donor feces was endoscopically administered. The efficacy of FMT was evaluated after 8 weeks using the Mayo score, Crohn's Disease Activity Index (CDAI), and the absence of diarrhea with stool toxin negativity in patients with active UC, CD, and rCDI, respectively. For fecal microbiota analysis, the 16S ribosomal RNA gene was sequenced, and fecal SCFA levels were measured.
Results: Clinical response was achieved in 5/20 (25%), 3/4 (75%), and 4/4 (100%) patients with UC, CD, and rCDI, respectively. Clinical remission was achieved in 4/20 (20%) and 1/4 (25%) patients with UC and CD, respectively. Linear discriminant analysis illustrated that UC responders had lower counts of Clostridium cluster XIVa before FMT and higher counts after FMT. Higher Fusicatenibacter saccharivorans counts in donors were significantly correlated with 8-week clinical remission. Patients with CD exhibited lower Blautia, Dorea, and Eubacterium counts before FMT and higher Collinsella, Dorea, and Eubacterium counts after FMT, accompanied by functional profiles predictive of SCFA fermentation and elevated fecal butyrate concentrations. Patients with rCDI displayed significantly lower abundances of Clostridium clusters IV and XIVa before FMT and higher abundances after FMT accompanied by elevated fecal propionate concentrations.
Conclusions: FMT exhibited various efficacy against UC, CD, and rCDI by altering the gut microbiota and SCFA production.}, }
@article {pmid35109028, year = {2021}, author = {Cope, EK and Borsom, EM and Bolyen, EK and Jaramillo, SA and Conn, KA and Dillon, MR and Orsini, GM and Hirsch, AH and Lee, K and Caporaso, JG}, title = {Influence of fecal microbiota transplantation on gut microbiota composition and neuroinflammation of 3xTg-AD mice.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {17 Suppl 3}, number = {}, pages = {e054648}, doi = {10.1002/alz.054648}, pmid = {35109028}, issn = {1552-5279}, abstract = {BACKGROUND: The gut microbiota, the aggregate of all microbial cells that inhabit the gut, bidirectionally communicates with the brain via cytokines, neurotransmitters, hormones, and secondary metabolites via the gut-brain axis. The gut microbiota is thought to contribute to the development of Alzheimer's disease (AD), characterized by plaque deposition, neurofibrillary tangles, and neuroinflammation. We hypothesize that manipulation of the gut microbiota can alter development of AD pathologies and neuroinflammation via the gut microbiota-brain axis.
METHODS: To further elucidate the role of the gut-brain axis in AD, we performed fecal microbiota transplants (FMT) from aged (52-64 weeks) 3xTg-AD mice, modeling plaques and neurofibrillary tangles, to young 3xTg-AD (n=5) or wild-type mice (n=10). Phosphate buffered saline (PBS) was gavaged into 3xTg-AD (n=5) and wild-type mice (n=10) as a control. For FMT, a fecal slurry from aged 3xTg-AD mice was prepared and given to experimental mice via oral gavage. At 8 weeks, mice were gavaged with FMT or PBS for 5 consecutive days, followed by fortnightly maintenance transplants for 24 weeks. The V4 region of the 16S rRNA gene was sequenced on the Illumina MiSeq. Data were analyzed using QIIME 2. Reverse transcriptase qPCR was used to assess microgliosis, astrocytosis, and Th1/Th2 inflammation in the hippocampus of the FMT cohort at 24 weeks of age.
RESULTS: Our results show a shift in microbiome composition in FMT-treated mice when compared to control (PBS-treated) mice. Bacteroides were increased in 3xTg-AD and wild-type mice receiving FMT. At 24 weeks of age, there was no difference in neuroinflammation between mice treated with FMT compared to control (PBS) in 3xTg-AD or wild type mice. We observed partial engraftment of the gut microbiota from aged 3xTg-AD mice in all FMT-treated mice.
CONCLUSIONS: We demonstrate the ability to transplant an aged gut microbiome into young mice, however we did not observe changes in neuroinflammation at 24 weeks of age. Future studies will evaluate neuroinflammation and neuropathologies at later time points. These studies will contribute to our understanding of how features of the gut microbiota may contribute to AD development.}, }
@article {pmid34076695, year = {2021}, author = {Sanders, DJ and Inniss, S and Sebepos-Rogers, G and Rahman, FZ and Smith, AM}, title = {The role of the microbiome in gastrointestinal inflammation.}, journal = {Bioscience reports}, volume = {41}, number = {6}, pages = {}, pmid = {34076695}, issn = {1573-4935}, mesh = {Animals ; Autoimmune Diseases/immunology/metabolism/microbiology/therapy ; Bacteria/immunology/*metabolism ; Celiac Disease/immunology/metabolism/microbiology/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/immunology/metabolism/*microbiology/therapy ; *Gastrointestinal Microbiome ; Humans ; Immunity, Mucosal ; Inflammation Mediators/metabolism ; Inflammatory Bowel Diseases/immunology/metabolism/microbiology/therapy ; Intestines/immunology/metabolism/*microbiology ; Metabolic Syndrome/immunology/metabolism/microbiology/therapy ; Pathogen-Associated Molecular Pattern Molecules/metabolism ; Probiotics/therapeutic use ; Signal Transduction ; }, abstract = {The microbiome plays an important role in maintaining human health. Despite multiple factors being attributed to the shaping of the human microbiome, extrinsic factors such diet and use of medications including antibiotics appear to dominate. Mucosal surfaces, particularly in the gut, are highly adapted to be able to tolerate a large population of microorganisms whilst still being able to produce a rapid and effective immune response against infection. The intestinal microbiome is not functionally independent from the host mucosa and can, through presentation of microbe-associated molecular patterns (MAMPs) and generation of microbe-derived metabolites, fundamentally influence mucosal barrier integrity and modulate host immunity. In a healthy gut there is an abundance of beneficial bacteria that help to preserve intestinal homoeostasis, promote protective immune responses, and limit excessive inflammation. The importance of the microbiome is further highlighted during dysbiosis where a loss of this finely balanced microbial population can lead to mucosal barrier dysfunction, aberrant immune responses, and chronic inflammation that increases the risk of disease development. Improvements in our understanding of the microbiome are providing opportunities to harness members of a healthy microbiota to help reverse dysbiosis, reduce inflammation, and ultimately prevent disease progression.}, }
@article {pmid35108315, year = {2022}, author = {Liu, L and Fu, Q and Li, T and Shao, K and Zhu, X and Cong, Y and Zhao, X}, title = {Gut microbiota and butyrate contribute to nonalcoholic fatty liver disease in premenopause due to estrogen deficiency.}, journal = {PloS one}, volume = {17}, number = {2}, pages = {e0262855}, doi = {10.1371/journal.pone.0262855}, pmid = {35108315}, issn = {1932-6203}, abstract = {The incidence of nonalcoholic fatty liver disease (NAFLD) in postmenopausal women has increased significantly. Estrogen plays a very important role in NAFLD, but whether NAFLD in premenopausal women was caused by estrogen deficiency was unknown. Thus, it is of great clinical significance to explore the mechanism of NAFLD in premenopausal women. Gut microbiota and its metabolites short chain fatty acids (SCFA) have been shown to play important roles in the development of NAFLD. In this study, we investigated the impact of gut microbiota and SCFA in NAFLD patients and mice caused by estrogen deficiency. We showed that premenopause NAFLD patients had much lower estrogen levels. Estrogen deficient mice, due to ovariectomy (OVX), suffered more severe liver steatosis with an elevated body weight, abdominal fat weight, serum triglycerides and deterioration in hepatic steatosis. Altered gut microbiota composition and decreased butyrate content were found in NAFLD patients and in OVX mice. Furthermore, fecal microbiota transplantation (FMT) or supplementing with butyrate alleviated NAFLD in OVX mice. The production of antimicrobial peptides (AMP) Reg3ɣ, β-defensins and the expression of intestinal epithelial tight junction, including ZO-1 and Occluding-5, were decreased in the OVX mice compared to control mice. Upregulation of PPAR-ɣ and VLDLR, downregulation of PPAR-ɑ indicated that OVX mice suffered from abnormal lipid metabolism. These data indicate that changes in the gut microbiota and SCFA caused by estrogen reduction, together with a disorder in AMP production and lipid metabolism, promote NAFLD, thus provide SCFAs derived from microbiota as new therapeutic targets for the clinical prevention and treatment of NAFLD.}, }
@article {pmid35108241, year = {2022}, author = {Elhusein, AM and Fadlalmola, HA}, title = {Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome Patients: An Updated Systematic Review and Meta-Analysis.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {45}, number = {1}, pages = {11-20}, pmid = {35108241}, issn = {1538-9766}, abstract = {Irritable bowel syndrome (IBS) is a chronic gastrointestinal disease characterized by abdominal discomfort and bloating, diarrhea, and/or constipation. Fecal microbiota transplantation (FMT) is transferring the fecal bacteria and other microorganisms from a healthy person to another. We performed this systematic review and meta-analysis to assess the efficacy of FMT in treating IBS patients. We searched Scopus, PubMed, Cochrane, and Web of Science databases through June 2021 using relevant key words. We included 19 studies. Fecal microbiota transplantation was significantly superior to placebo in IBS quality of life after 4 weeks (mean difference [MD] = 7.47, 95% confidence interval [CI]: 2.05-12.89, p = .04), 12 weeks (MD = 9.99, 95% CI: 5.78-14.19, p < .00001), and 24 weeks (MD = 8.49, 95% CI: 0.47-16.52, p = .04), with no difference regarding IBS improvement symptoms and the IBS Severity Scoring System (SSS). Single-arm analysis revealed that the incidence of improvement of IBS symptoms was 57.8% (45.6%-69.9%) with reduction in IBS-SSS (MD = -74, 95% CI: -101.7 to -46.3). Fecal microbiota transplantation was superior to placebo in improving quality of life after 4, 12, and 24 weeks. Also, FMT improved IBS symptoms and reduced the IBS-SSS score. However, no deference was detected between FMT and placebo in IBS-SSS score and IBS symptoms improvement.}, }
@article {pmid35104764, year = {2022}, author = {Zhou, H and Zhao, J and Liu, C and Zhang, Z and Zhang, Y and Meng, D}, title = {Xanthoceraside exerts anti-Alzheimer's disease effect by remodeling gut microbiota and modulating microbial-derived metabolites level in rats.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {98}, number = {}, pages = {153937}, doi = {10.1016/j.phymed.2022.153937}, pmid = {35104764}, issn = {1618-095X}, abstract = {BACKGROUND: Microbial-derived metabolites play important roles in Alzheimer's disease (AD) pathology, yet how intestinal microbes influence AD progression remains uncertain. Xanthoceraside (XAN), a triterpenoid saponin with anti-AD activity, was extracted from the husks of Xanthoceras sorbifolia Bunge. However, it is still unclear that how XAN modulates the gut microbiota community to regulate AD progression through changing the levels of microbial-derived metabolites.
PURPOSE: In this study, we investigated the mechanism underlying the anti-AD effect of XAN.
METHODS: The current combination studies of multiple-targeted metabolomics, natural product chemistry and pharmacology revealed that oral XAN mediated intestinal microbiota to ameliorate Aβ1-42-induced learning and memory deficits in rats, which were confirmed through antibiotic treatments and fecal microbiota transplantation.
RESULTS: As a poor water solubility and low permeability compound that hardly be absorbed into blood-brain barrier, XAN significantly regulated Aβ1-42-induced metabolism disorders directly or indirectly in gut, including neurotransmitters, amino acids, bile acids and SCFAs metabolism that were detected by UHPLC-MS/MS and GC-MS/MS. In particularly, the in vitro evaluation of XAN on SCFAs production not only found a striking increase in the production of SCFAs after fermentation, but revealed the inner relationship among XAN, gut microbiota and SCFAs in vivo. All results demonstrated that XAN could improve AD rats' learning and memory deficits by modulating the community of gut microbiota which was connected through 16S rRNA sequencing and CCA analyses.
CONCLUSIONS: Our study provided a novel mechanism for developing XAN as a potential anti-AD drug and revealed that the gut microbiota might be a potential target for AD treatment .}, }
@article {pmid35096856, year = {2021}, author = {Savigamin, C and Mahakit, N and Stithit, S and Samuthpongtorn, C}, title = {How to Initiate Fecal Microbiota Transplantation in Developing Countries Using the Behavior Economics Concept of "Choice Architecture".}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {746230}, doi = {10.3389/fmed.2021.746230}, pmid = {35096856}, issn = {2296-858X}, }
@article {pmid35094316, year = {2022}, author = {Abuaish, S and Al-Otaibi, NM and Aabed, K and Abujamel, TS and Alzahrani, SA and Alotaibi, SM and Bhat, RS and Arzoo, S and Algahtani, N and Moubayed, NM and El-Ansary, A}, title = {The Efficacy of Fecal Transplantation and Bifidobacterium Supplementation in Ameliorating Propionic Acid-Induced Behavioral and Biochemical Autistic Features in Juvenile Male Rats.}, journal = {Journal of molecular neuroscience : MN}, volume = {}, number = {}, pages = {}, pmid = {35094316}, issn = {1559-1166}, support = {RGP-1441-0027//This research project was funded by the Deanship of Scientific Research, Princess Nourah Bint Abdulrahman University, Grant number RGP-1441-0027/ ; }, abstract = {Gut microbiota plays a major role in neurological disorders, including autism. Modulation of the gut microbiota through fecal microbiota transplantation (FMT) or probiotic administration, such as Bifidobacteria, is suggested to alleviate autistic symptoms; however, their effects on the brain are not fully examined. We tested both approaches in a propionic acid (PPA) rodent model of autism as treatment strategies. Autism was induced in Sprague-Dawley rats by administering PPA orally (250 mg/kg) for 3 days. Animals were later treated with either saline, FMT, or Bifidobacteria for 22 days. Control animals were treated with saline throughout the study. Social behavior and selected brain biochemical markers related to stress hormones, inflammation, and oxidative stress were assessed. PPA treatment induced social impairments, which was rescued by the treatments. In the brain, Bifidobacteria treatment increased oxytocin relative to control and PPA groups. Moreover, Bifidobacteria treatment rescued the PPA-induced increase in IFN-γ levels. Both treatments increased GST levels, which was diminished by the PPA treatment. These findings indicate the potential of gut microbiota-targeted therapeutics in ameliorating behavioral deficit and underlying neural biochemistry.}, }
@article {pmid35093952, year = {2022}, author = {Gallo, A and Macerola, N and Favuzzi, AMR and Nicolazzi, MA and Gasbarrini, A and Montalto, M}, title = {The Gut in Heart Failure: Current Knowledge and Novel Frontiers.}, journal = {Medical principles and practice : international journal of the Kuwait University, Health Science Centre}, volume = {}, number = {}, pages = {}, doi = {10.1159/000522284}, pmid = {35093952}, issn = {1423-0151}, abstract = {Heart failure (HF) represents a major health problem affecting million people worldwide. In the latest years, many efforts have been made to search more effective strategies to prevent and modify the course of disease, but results are still not satisfying. HF represents a complex clinical syndrome involving many other systems, including the gastrointestinal one. Although the relationship between gut and HF is far from being fully understood, based on recent evidences highlighting the putative role of gastrointestinal system in different cardiovascular diseases, it is conceivable that the link gut-heart may represent the basis for novel therapeutic approaches also in the HF context. This intricate interplay involving typical hemodynamic changes and their consequences on gut morphology, permeability and function, sets the stage for microbiota composition alterations, able to impact on HF mechanisms through different routes, such as bacterial translocation and metabolic pathways. Therefore, the modulation of the gut microbiota through diet, probiotics and fecal transplantation, has been suggested as a potential therapeutic approach. More interestingly, another effect of alteration in microbiota composition reflects in the upregulation of co-transporters (NHE3) with consequent salt and fluids overload and worsening visceral congestion. In this light, the inhibitors of this co-transporter may also represent a novel therapeutic frontier. By review of more recent available data on this topic, we describe the current state of the complex interplay between gastrointestinal and cardiac systems in heart failure, and the relevance of these understandings in seeking new therapeutic strategies.}, }
@article {pmid35092426, year = {2022}, author = {Guzzo, GL and Andrews, JM and Weyrich, LS}, title = {The Neglected Gut Microbiome: Fungi, Protozoa, and Bacteriophages in Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izab343}, pmid = {35092426}, issn = {1536-4844}, abstract = {The gut microbiome has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Studies suggest that the IBD gut microbiome is less diverse than that of the unaffected population, a phenomenon often referred to as dysbiosis. However, these studies have heavily focused on bacteria, while other intestinal microorganisms-fungi, protozoa, and bacteriophages-have been neglected. Of the nonbacterial microbes that have been studied in relation to IBD, most are thought to be pathogens, although there is evidence that some of these species may instead be harmless commensals. In this review, we discuss the nonbacterial gut microbiome of IBD, highlighting the current biases, limitations, and outstanding questions that can be addressed with high-throughput DNA sequencing methods. Further, we highlight the importance of studying nonbacterial microorganisms alongside bacteria for a comprehensive view of the whole IBD biome and to provide a more precise definition of dysbiosis in patients. With the rise in popularity of microbiome-altering therapies for the treatment of IBD, such as fecal microbiota transplantation, it is important that we address these knowledge gaps to ensure safe and effective treatment of patients.}, }
@article {pmid35091345, year = {2022}, author = {Wortelboer, K and Bakker, GJ and Winkelmeijer, M and van Riel, N and Levin, E and Nieuwdorp, M and Herrema, H and Davids, M}, title = {Fecal microbiota transplantation as tool to study the interrelation between microbiota composition and miRNA expression.}, journal = {Microbiological research}, volume = {257}, number = {}, pages = {126972}, doi = {10.1016/j.micres.2022.126972}, pmid = {35091345}, issn = {1618-0623}, abstract = {The intestinal gut microbiota is important for human metabolism and immunity and can be influenced by many host factors. A recently emerged host factor is secreted microRNA (miRNA). Previously, it has been shown that secreted miRNAs can influence the growth of certain bacteria and conversely, that shifts in the microbiota can alter the composition of secreted miRNAs. Here, we sought to further investigate the interaction between the gut microbiota and secreted miRNAs by the use of fecal microbiota transplantation (FMT). Subjects with the metabolic syndrome received either an autologous (n = 4) or allogenic (n = 14) FMT. Fecal samples were collected at baseline and 6 weeks after FMT, from which the microbiome and miRNA composition were determined via 16S rRNA sequencing and miRNA sequencing, respectively. We observed a significant correlation between the fecal miRNA expression and microbiota composition, both before and after FMT. Our results suggest that the FMT-induced shift in microbiota altered the fecal miRNA profile, indicated by correlations between differentially abundant microbes and miRNAs. This idea of a shift in miRNA composition driven by changes in the microbiota was further strengthened by the absence of a direct effect of specific miRNAs on the growth of specific bacterial strains.}, }
@article {pmid35090836, year = {2022}, author = {Mu, C and Choudhary, A and Mayengbam, S and Barrett, KT and Rho, JM and Shearer, J and Scantlebury, MH}, title = {Seizure modulation by the gut microbiota and tryptophan-kynurenine metabolism in an animal model of infantile spasms.}, journal = {EBioMedicine}, volume = {}, number = {}, pages = {103833}, doi = {10.1016/j.ebiom.2022.103833}, pmid = {35090836}, issn = {2352-3964}, abstract = {BACKGROUND: The infantile spasms syndrome is an early-onset epileptic encephalopathy presenting in the first 2 years of life, often with severe developmental consequences. The role of the gut microbiota and metabolism in infantile spasms remains unexplored.
METHODS: Employing a brain injury neonatal rat model of infantile spasms intractable to anticonvulsant medication treatments, we determined how the ketogenic diet and antibiotics affected specific microbial communities and the resultant circulating factors that confer spasms protection in the infantile spasms model. To confirm a role of kynurenine metabolism pathway in spasms protection, indoleamine 2,3-dioxygenase 1 was pharmacologically inhibited and comprehensive metabolomics was applied.
FINDINGS: We show that antibiotics reduced spasms and improved the effectiveness of the ketogenic diet when given in combination. Examination of the gut microbiota and metabolomics showed the downregulation of indoleamine 2,3-dioxygenase 1 and upregulation of hippocampal kynurenic acid, a metabolite with antiepileptic effects. To further test the involvement of indoleamine 2,3-dioxygenase 1, a specific antagonist 1-methyltryptophan and minocycline, an antibiotic and inhibitor of kynurenine formation from tryptophan, were administered, respectively. Both treatments were effective in reducing spasms and elevating hippocampal kynurenic acid. A fecal microbiota transplant experiment was then performed to examine the contribution of the gut microbiota on spasm mitigation. Transplant of feces of ketogenic diet animals into normal diet animals was effective in reducing spasms.
INTERPRETATION: These results highlight the importance of tryptophan-kynurenine metabolism in infantile spasms and provide evidence for new-targeted therapies such as indoleamine 2,3-dioxygenase 1 inhibition or microbiota manipulation to promote kynurenic acid production as a strategy to reduce spasms in infantile spasms.
FUNDING: This study was funded by the Alberta Children's Hospital Research Institute and the Owerko Centre.}, }
@article {pmid34751848, year = {2022}, author = {Donahue, CA and Chaudhry, V and Mantilla, N}, title = {Autologous fecal transplant for the treatment of microcolon due to diversion colitis.}, journal = {Techniques in coloproctology}, volume = {26}, number = {1}, pages = {79-81}, pmid = {34751848}, issn = {1128-045X}, mesh = {*Colitis/etiology/therapy ; Colon/abnormalities ; Fecal Microbiota Transplantation ; Humans ; *Intestinal Obstruction ; }, }
@article {pmid34236075, year = {2021}, author = {Stott, KJ and Phillips, B and Parry, L and May, S}, title = {Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer.}, journal = {Bioscience reports}, volume = {41}, number = {7}, pages = {}, doi = {10.1042/BSR20204113}, pmid = {34236075}, issn = {1573-4935}, support = {C23498/A27517/CRUK_/Cancer Research UK/United Kingdom ; A17196/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Bacteria/*drug effects/growth & development/metabolism/pathogenicity ; Colorectal Neoplasms/metabolism/microbiology/*therapy ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Humans ; Probiotics/adverse effects/*therapeutic use ; Treatment Outcome ; }, abstract = {Over the last few decades it has been established that the complex interaction between the host and the multitude of organisms that compose the intestinal microbiota plays an important role in human metabolic health and disease. Whilst there is no defined consensus on the composition of a healthy microbiome due to confounding factors such as ethnicity, geographical locations, age and sex, there are undoubtably populations of microbes that are consistently dysregulated in gut diseases including colorectal cancer (CRC). In this review, we discuss the most recent advances in the application of the gut microbiota, not just bacteria, and derived microbial compounds in the diagnosis of CRC and the potential to exploit microbes as novel agents in the management and treatment of CRC. We highlight examples of the microbiota, and their derivatives, that have the potential to become standalone diagnostic tools or be used in combination with current screening techniques to improve sensitivity and specificity for earlier CRC diagnoses and provide a perspective on their potential as biotherapeutics with translatability to clinical trials.}, }
@article {pmid34214453, year = {2022}, author = {Watane, A and Cavuoto, KM and Rojas, M and Dermer, H and Day, JO and Banerjee, S and Galor, A}, title = {Fecal Microbial Transplant in Individuals With Immune-Mediated Dry Eye.}, journal = {American journal of ophthalmology}, volume = {233}, number = {}, pages = {90-100}, pmid = {34214453}, issn = {1879-1891}, support = {R01 EY026174/EY/NEI NIH HHS/United States ; P30 EY014801/EY/NEI NIH HHS/United States ; I01 BX004893/BX/BLRD VA/United States ; R61 EY032468/EY/NEI NIH HHS/United States ; I01 CX002015/CX/CSRD VA/United States ; }, mesh = {*Dry Eye Syndromes/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Male ; *Microbiota ; Middle Aged ; Treatment Outcome ; }, abstract = {PURPOSE: To evaluate the safety of the Fecal Microbial Transplant for Sjogren Syndrome (FMT) trial in individuals with immune-mediated dry eye (DE).
DESIGN: Open-label, nonrandomized clinical trial.
METHODS: The study population included 10 individuals with DE symptoms and signs meeting criteria for Sjögren or positive early Sjögren markers. Procedures were 2 FMTs from a single healthy donor delivered via enema, 1 week apart. The primary outcome measure was safety. In addition, gut microbiome profiles, DE metrics, and T-cell profiles in blood were examined at baseline before FMT, and at 1 week, 1 month, and 3 months after FMT.
RESULTS: The mean age of the population was 60.4 years; 30% were male; 50% were white; and 50% were Hispanic. At baseline, all subjects had significantly different gut microbiome profiles from the donor, including higher mean diversity indices. Subjects had a decreased abundance of genera Faecalibacterium, Prevotella, and Ruminococcus and an increased abundance of genera Alistipes, Streptococcus, and Blautia compared to the donor. Effector and regulatory T-cell profiles were positively correlated with each other and with DE symptom severity (T helper 1 cells [Th1]; r = .76; P = .01; Th17: r = 0.83; P = .003; CD25: r = 0.66; P = .04; FoxP3: r = 0.68; P = .03). No adverse events were noted with FMT. After FMT, gut microbiome profiles in 8 subjects moved closer to the donor's profile. As a group, gut microbiome profiles at all follow-up time points were more similar to the original recipients' than the donor's microbiome; however, certain phyla, classes, and genera operational taxonomic unit (OTU) numbers remained closer to the donor vs recipients' baseline profiles out to 3 months. Five individuals subjectively reported improved dry eye symptoms 3 months after FMT.
CONCLUSIONS: FMT was safely performed in individuals with immune-mediated DE, with certain bacterial profiles resembling the donor out to 3 months after FMT. One-half the subjects reported improved DE symptoms. The most effective FMT administration method has yet to be determined.}, }
@article {pmid33744169, year = {2021}, author = {Bestfater, C and Vehreschild, MJGT and Stallmach, A and Tüffers, K and Erhardt, A and Frank, T and Glück, T and Goeser, F and Sellge, G and Solbach, P and Eisenlohr, H and Storr, M and , }, title = {Clinical effectiveness of bidirectional fecal microbiota transfer in the treatment of recurrent Clostridioides difficile infections.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {53}, number = {6}, pages = {706-711}, doi = {10.1016/j.dld.2021.02.022}, pmid = {33744169}, issn = {1878-3562}, mesh = {Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Registries ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transfer (FMT) has become a standard of care in the prevention of multiple recurrent Clostridioides difficile (rCDI) infection.
AIM: While primary cure rates range from 70-80% following a single treatment using monodirectional approaches, cure rates of combination treatment remain largely unknown.
METHODS: In a retrospective case-control study, outcomes following simultaneous bidirectional FMT (bFMT) with combined endoscopic application into the upper and lower gastrointestinal tract, compared to standard routes of application (endoscopy via upper or lower gastrointestinal tract and oral capsules; abbreviated UGIT, LGIT and CAP) on day 30 and 90 after FMT were assessed. Statistical matching partners were identified using number of recurrences (<3; ≥3), age and gender.
RESULTS: Primary cure rates at D30 and D90 for bFMT were 100% (p=.001). The matched control groups showed cure rates of 81.3% for LGIT (p=.010), 62.5% for UGIT (p=.000) and 78.1% for CAP (p=.005) on D30 and 81.3% for LGIT (p=.010), 59.4% for UGIT (p=.000) and 71.9% for CAP (p=.001) on D90.
CONCLUSION: In our analysis, bFMT on the same day significantly increased primary cure rate at D30 and D90. These data require prospective confirmation but suggest that route of application may play a significant role in optimizing patient outcomes. ClinicalTrials.gov no: NCT02681068.}, }
@article {pmid35088527, year = {2022}, author = {Li, XL and Cui, JJ and Zheng, WS and Zhang, JL and Li, R and Ma, XL and Lin, M and Guo, HH and Li, C and Yu, XY and Du, P and Zhao, LM and He, S and Lan, P and Jiang, JD and Che, Y and Wang, LL}, title = {Bicyclol Alleviates Atherosclerosis by Manipulating Gut Microbiota.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {}, number = {}, pages = {e2105021}, doi = {10.1002/smll.202105021}, pmid = {35088527}, issn = {1613-6829}, support = {2019YFC170890//National Key R&D Project/ ; 81621064//National Natural Science Foundation of China/ ; 2021-I2M-1-009//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-1-030//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-1-070//CAMS Innovation Fund for Medical Sciences/ ; 2018ZX09721003-008-026//National Sciences and Technology Major Project/ ; }, abstract = {Atherosclerosis (AS) is associated with high morbidity and mortality, thus imposing a growing burden on modern society. Herb-derived bicyclol (BIC) is a versatile bioactive compound that can be used to treat AS. However, its efficacy in AS is not yet described. Here, it is shown that BIC normalizes gut microflora dysbiosis induced by a high fat diet in Apoe(-/-) mice. Metagenome-wide association study analysis verifies that the modulation on carbohydrate-active enzymes and short-chain fatty acid generating genes in gut flora is among the mechanisms. The gut healthiness, especially the gut immunity and integrity, is restored by BIC intervention, leading to improved systemic immune cell dynamic and liver functions. Accordingly, the endothelial activation, macrophage infiltration, and cholesterol ester accumulation in the aortic arch are alleviated by BIC to lessen the plaque onset. Moreover, it is proved that the therapeutic effect of BIC on AS is transmissible by fecal microbiota transplantation. The current study, for the first time, demonstrates the antiatherosclerotic effects of BIC and shows that its therapeutic value can at least partially be attributed to its manipulation of gut microbiota.}, }
@article {pmid35086768, year = {2022}, author = {Servetas, SL and Daschner, PJ and Guyard, C and Thomas, V and Affagard, H and Sergaki, C and Sokol, H and Wargo, JA and Wu, GD and Sabot, P}, title = {Evolution of FMT - From early clinical to standardized treatments.}, journal = {Biologicals : journal of the International Association of Biological Standardization}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.biologicals.2022.01.004}, pmid = {35086768}, issn = {1095-8320}, abstract = {Faecal microbiota transplantation (FMT) is widely reported to be an effective treatment against recurrent Clostridioides difficile infections. Recent clinical studies support the therapeutic use of FMT for several other pathologies including inflammatory bowel disease, several types of cancer, and other functional or metabolic disorders. Initial guidelines are now available to overcome some of the technical and logistical issues for establishing a non-standardized treatment into clinical practice with proper safety and governance. To aid the improvement of guidance and standardization requirements for FMT, the International Alliance for Biological Standardization (IABS) and the BIOASTER Microbiology Technology Institute hosted a joint online workshop in May of 2021. The goal of the webinar was to provide a multi-disciplinary perspective of the ongoing efforts to develop FMT guidelines including technical, regulatory, and standardization requirements. Recognized experts gave insights into state-of-the art approaches and standards developed by international organizations and institutions.}, }
@article {pmid34880269, year = {2021}, author = {Parker-Character, J and Hager, DR and Call, TB and Pickup, ZS and Turnbull, SA and Marshman, EM and Korch, SB and Chaston, JM and Call, GB}, title = {An altered microbiome in a Parkinson's disease model Drosophila melanogaster has a negative effect on development.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {23635}, pmid = {34880269}, issn = {2045-2322}, mesh = {Animals ; Disease Models, Animal ; Drosophila Proteins/genetics ; Drosophila melanogaster/*growth & development/*microbiology ; Fecal Microbiota Transplantation ; Female ; Male ; *Microbiota ; Parkinson Disease/*microbiology ; Ubiquitin-Protein Ligases/genetics ; }, abstract = {Parkinson's disease (PD) is the second most common neurodegenerative disease, besides Alzheimer's Disease, characterized by multiple symptoms, including the well-known motor dysfunctions. It is well-established that there are differences in the fecal microbiota composition between Parkinson's disease (PD) patients and control populations, but the mechanisms underlying these differences are not yet fully understood. To begin to close the gap between description and mechanism we studied the relationship between the microbiota and PD in a model organism, Drosophila melanogaster. First, fecal transfers were performed with a D. melanogaster model of PD that had a mutation in the parkin (park25) gene. Results indicate that the PD model feces had a negative effect on both pupation and eclosion in both control and park25 flies, with a greater effect in PD model flies. Analysis of the microbiota composition revealed differences between the control and park25 flies, consistent with many human studies. Conversely, gnotobiotic treatment of axenic embryos with feces-derived bacterial cultures did not affect eclosure. We speculate this result might be due to similarities in bacterial prevalence between mutant and control feces. Further, we confirmed a bacteria-potentiated impact on mutant and control fly phenotypes by measuring eclosure rate in park25 flies that were mono-associated with members of the fly microbiota. Both the fecal transfer and the mono-association results indicate a host genotype-microbiota interaction. Overall, this study concludes functional effects of the fly microbiota on PD model flies, providing support to the developing body of knowledge regarding the influence of the microbiota on PD.}, }
@article {pmid34758276, year = {2022}, author = {Moutsoglou, DM}, title = {2021 American Thoracic Society BEAR Cage Winning Proposal: Microbiome Transplant in Pulmonary Arterial Hypertension.}, journal = {American journal of respiratory and critical care medicine}, volume = {205}, number = {1}, pages = {13-16}, doi = {10.1164/rccm.202108-1833ED}, pmid = {34758276}, issn = {1535-4970}, mesh = {Administration, Oral ; *Awards and Prizes ; Clinical Protocols ; Clinical Trials, Phase I as Topic/*methods ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; Pulmonary Arterial Hypertension/*microbiology/*therapy ; Societies, Medical ; }, }
@article {pmid34523250, year = {2021}, author = {Liu, C and Cheung, WH and Li, J and Chow, SK and Yu, J and Wong, SH and Ip, M and Sung, JJY and Wong, RMY}, title = {Understanding the gut microbiota and sarcopenia: a systematic review.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {12}, number = {6}, pages = {1393-1407}, pmid = {34523250}, issn = {2190-6009}, mesh = {Aged ; Animals ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Prebiotics ; *Sarcopenia/etiology/therapy ; *Synbiotics ; }, abstract = {BACKGROUND: Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut-muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia.
METHODS: A systematic review was performed in PubMed, Embase, Web of Science, and The Cochrane Library databases using the keywords (microbiota* OR microbiome*) AND (sarcopen* OR muscle). Studies reporting the alterations of gut microbiota and muscle/physical performance were analysed.
RESULTS: A total of 26 pre-clinical and 10 clinical studies were included. For animal studies, three revealed age-related changes and relationships between gut microbiota and muscle. Three studies focused on muscle characteristics of germ-free mice. Seventy-five per cent of eight faecal microbiota transplantation studies showed that the recipient mice successfully replicated the muscle phenotype of donors. There were positive effects on muscle from seven probiotics, two prebiotics, and short-chain fatty acids (SCFAs). Ten studies investigated on other dietary supplements, antibiotics, exercise, and food withdrawal that affected both muscle and gut microbiota. Twelve studies explored the potential mechanisms of the gut-muscle axis. For clinical studies, 6 studies recruited 676 elderly people (72.8 ± 5.6 years, 57.8% female), while 4 studies focused on 244 young adults (29.7 ± 7.8 years, 55.4% female). The associations of gut microbiota and muscle had been shown in four observational studies. Probiotics, prebiotics, synbiotics, fermented milk, caloric restriction, and exercise in six studies displayed inconsistent effects on muscle mass, function, and gut microbiota.
CONCLUSIONS: Altering the gut microbiota through bacteria depletion, faecal transplantation, and various supplements was shown to directly affect muscle phenotypes. Probiotics, prebiotics, SCFAs, and bacterial products are potential novel therapies to enhance muscle mass and physical performance. Lactobacillus and Bifidobacterium strains restored age-related muscle loss. Potential mechanisms of microbiome modulating muscle mainly include protein, energy, lipid, and glucose metabolism, inflammation level, neuromuscular junction, and mitochondrial function. The role of the gut microbiota in the development of muscle loss during aging is a crucial area that requires further studies for translation to patients.}, }
@article {pmid34704376, year = {2022}, author = {Zhu, L and Fu, J and Xiao, X and Wang, F and Jin, M and Fang, W and Wang, Y and Zong, X}, title = {Faecal microbiota transplantation-mediated jejunal microbiota changes halt high-fat diet-induced obesity in mice via retarding intestinal fat absorption.}, journal = {Microbial biotechnology}, volume = {15}, number = {1}, pages = {337-352}, pmid = {34704376}, issn = {1751-7915}, mesh = {Animals ; Diet, High-Fat/adverse effects ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Jejunum ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Obesity/therapy ; }, abstract = {Faecal Microbiota Transplantation (FMT) is considered as a promising technology to fight against obesity. Wild boar has leanermuscle and less fat in comparison to the domestic pig, which were thought to be related with microbiota. To investigate the function and mechanism of the wild boar microbiota on obesity, we first analysed the wild boar microbiota composition via 16S rDNA sequencing, which showed that Firmicutes and Proteobacteria were the dominant bacteria. Then, we established a high-fat diet (HFD)-induced obesity model, and transfer low and high concentrations of wild boar faecal suspension in mice for 9 weeks. The results showed that FMT prevented HFD-induced obesity and lipid metabolism disorders, and altered the jejunal microbiota composition especially increasing the abundance of the Lactobacillus and Romboutsia, which were negatively correlated with obesity-related indicators. Moreover, we found that the anti-obesity effect of wild boar faecal suspension was associated with jejunal N6-methyladenosine (m6 A) levels. Overall, these results suggest that FMT has a mitigating effect on HFD-induced obesity, which may be due to the impressive effects of FMT on the microbial composition and structure of the jejunum. These changes further alter intestinal lipid metabolism and m6 A levels to achieve resistance to obesity.}, }
@article {pmid34160593, year = {2021}, author = {Raine, T and Verstockt, B and Kopylov, U and Karmiris, K and Goldberg, R and Atreya, R and Burisch, J and Burke, J and Ellul, P and Hedin, C and Holubar, SD and Katsanos, K and Lobaton, T and Schmidt, C and Cullen, G}, title = {ECCO Topical Review: Refractory Inflammatory Bowel Disease.}, journal = {Journal of Crohn's & colitis}, volume = {15}, number = {10}, pages = {1605-1620}, doi = {10.1093/ecco-jcc/jjab112}, pmid = {34160593}, issn = {1876-4479}, support = {//ECCO/ ; }, mesh = {Biological Factors/therapeutic use ; Diet ; Digestive System Surgical Procedures ; Fecal Microbiota Transplantation ; Gastrointestinal Agents/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents/therapeutic use ; Inflammatory Bowel Diseases/diagnosis/*therapy ; Medication Adherence ; Mesenchymal Stem Cell Transplantation ; Patient Care Team ; Remission Induction ; }, abstract = {Inflammatory bowel disease is a chronic disease with variable degrees of extent, severity, and activity. A proportion of patients will have disease that is refractory to licensed therapies, resulting in significant impairment in quality of life. The treatment of these patients involves a systematic approach by the entire multidisciplinary team, with particular consideration given to medical options including unlicensed therapies, surgical interventions, and dietetic and psychological support. The purpose of this review is to guide clinicians through this process and provide an accurate summary of the available evidence for different strategies.}, }
@article {pmid35077579, year = {2022}, author = {Gu, Z and Xiong, Q and Wang, L and Wang, L and Li, F and Hou, C and Dou, L and Zhu, B and Liu, D}, title = {The impact of intestinal microbiota in antithymocyte globulin-based myeloablative allogeneic hematopoietic cell transplantation.}, journal = {Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/cncr.34091}, pmid = {35077579}, issn = {1097-0142}, support = {82070178//National Natural Science Foundation of China/ ; ZH19003//Military Translational Medicine Fund of Chinese PLA General Hospital/ ; }, abstract = {BACKGROUND: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HCT) has been reported in platforms with T-cell depletion or postcyclophosphamide-based graft-vs-host disease (GVHD) prophylaxis regimens. It is still unclear whether it is the same in platforms of antithymocyte globulin (ATG)-based myeloablative allo-HCT.
METHODS: A total of 603 fecal specimens from 100 consecutive patients receiving allo-HCT were collected between December 2018 and July 2020. Fetal samples were profiled with next-generation sequencing of bacterial 16S ribosomal RNA (rRNA) genes.
RESULTS: The diversity decreased to the lowest level at approximately day 12 after allo-HCT and then increased over time. According to the diversity of 314 samples that were collected from 86 patients during the engraftment period, patients were grouped into the low- and high-diversity groups. Two-year overall survival in the high-diversity group was significantly longer than that in the low-diversity group (83.7% vs 60.6%, P = .026). Further analysis revealed that worse outcomes for patients with low diversity were associated with increased risk of worse outcomes for patients with low diversity (adjusted hazard ratio, 4.95; P = .046). Its association with relapse and GVHD was not found. Compositional analysis of fecal microbiota revealed that the abundance of bacteroides decreased greatly during allo-HCT, whereas that of Enterococcus, Klebsiella, and Escherichia was found to be increased.
CONCLUSIONS: This study indicates that gut dysbiosis in platforms of ATG-based myeloablative allo-HCT featured loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period was an independent predictor of longer survival.
LAY SUMMARY: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HCT) is reported in platforms with T-cell depletion or postcyclophosphamide-based graft-vs-host disease (GVHD) prophylaxis regimens. It is still unclear whether it is the same pattern in platforms of antithymocyte globulin (ATG)-based T-cell repletion myeloablative allo-HCT. Our study indicated that gut dysbiosis in platforms of ATG-based myeloablative allo-HCT also features loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period is an independent predictor of longer survival.}, }
@article {pmid35077172, year = {2022}, author = {Wang, T and Shi, C and Wang, S and Zhang, Y and Wang, S and Ismael, M and Zhang, J and Wang, X and Lü, X}, title = {Protective Effects of Companilactobacillus crustorum MN047 against Dextran Sulfate Sodium-Induced Ulcerative Colitis: A Fecal Microbiota Transplantation Study.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.1c07316}, pmid = {35077172}, issn = {1520-5118}, abstract = {Gut microbiota dysbiosis could aggravate the development of ulcerative colitis (UC). Companilactobacillus crustorum MN047 (CCMN) is a potential gut microbiota-regulating probiotic that could produce multiple novel bacteriocins. In this study, fecal microbiota transplantation (FMT) was used to verify whether CCMN could alleviate dextran sulfate sodium-induced UC by regulating gut microbiota. Results showed that both CCMN and FMT ameliorated the symptoms of UC, including attenuating the increased disease activity index, shortened colon length, gut barrier damage, and inflammation. Briefly, CCMN and FMT upregulated the expressions of MUCs and tight junctions, downregulated the expressions of proinflammatory cytokines and chemokines, increased fecal short-chain fatty acids, and lowered serum lipopolysaccharides, which were associated with the regulation of gut microbiota (e.g., increased Akkermansia, Blautia, and Ruminococcus levels). These results demonstrated that CCMN could ameliorate UC by modulating gut microbiota and inhibiting the TLR4/NF-κB pathway. Therefore, CCMN could be considered as a potential probiotic supplement for ameliorating UC.}, }
@article {pmid35074739, year = {2022}, author = {Xu, J and Wang, M and Liu, Q and Lin, X and Pu, K and He, Z}, title = {Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice.}, journal = {Ecotoxicology and environmental safety}, volume = {231}, number = {}, pages = {113224}, doi = {10.1016/j.ecoenv.2022.113224}, pmid = {35074739}, issn = {1090-2414}, abstract = {Growing evidence indicates that exposure to high levels of nitrite for a prolonged time has adverse health effects. Although gut microbiota is responsible for the transformation of nitrite in the gut, the evidence concerning whether gut microbiota mediates the toxicity of nitrite is still lacking. The present study addressed the long-term effects of dietary nitrite on male C57BL/6 mice and employed fecal microbiota transplantation (FMT) to reveal whether gut microbiota mediated the effects of nitrite. Furthermore, the effect of azoxymethane (AOM) on gut microbiota was detected for mice drinking normal or nitrite-containing water. High nitrite had toxic effects on C57BL/6 mice. Meanwhile, high nitrite induced skin lesions in mice, accompanied with increased serum ALT, colon IL-6, TNF-α, and MDA levels, together with decreased serum Cr, colon sIgA, and T-AOC levels. After fecal microbiota was transplanted into the normal mice, the nitrite-regulated gut microbiota could also induce skin lesions, coupled with reduced serum Cr, and increased colon MDA. The high dose of nitrite caused the upregulations of Alistipes, Prevotella, and Ruminococcus, which could be transplanted into normal mice through FMT. Inversely, gut microbiota from normal mice reduced the effects of nitrite on serum ALT and Cr, together with colon sIgA and MDA. Gut microbiota from normal mice could also upregulate metabolic genes and downregulate stress genes in the nitrite-treated mice. It might due to the upregulation of Akkermansia and Parabacteroides caused by FMT from normal water-treated mice to nitrite-treated mice. In addition, AOM exhibited to be more toxic to the colon in the nitrite-treated mice in comparison with normal water-treated mice, and it might be due to the expression of Hspa1a and Hspa1b in the colon. Interestingly, gut microbiota was more influenced by AOM in the normal water-treated mice than the nitrite-treated mice. Overall, these data demonstrated that gut microbiota mediated the toxicity of a high concentration of dietary nitrite.}, }
@article {pmid35074372, year = {2022}, author = {Yan, J and Chen, Q and Tian, L and Li, K and Lai, W and Bian, L and Han, J and Jia, R and Liu, X and Xi, Z}, title = {Intestinal toxicity of micro- and nano-particles of foodborne titanium dioxide in juvenile mice: Disorders of gut microbiota-host co-metabolites and intestinal barrier damage.}, journal = {The Science of the total environment}, volume = {}, number = {}, pages = {153279}, doi = {10.1016/j.scitotenv.2022.153279}, pmid = {35074372}, issn = {1879-1026}, abstract = {The wide use of TiO2 particles in food and the high exposure risk to children have prompted research into the health risks of TiO2. We used the microbiome and targeted metabolomics to explore the potential mechanism of intestinal toxicity of foodborne TiO2 micro-/nanoparticles after oral exposure for 28 days in juvenile mice. Results showed that the gut microbiota-including the abundance of Bacteroides, Bifidobacterium, Lactobacillus, and Prevotella-changed dynamically during exposure. The organic inflammatory response was activated, and lipopolysaccharide levels increased. Intestinal toxicity manifested as increased mucosal permeability, impaired intestinal barrier, immune damage, and pathological changes. The expression of antimicrobial peptides, occludin, and ZO-1 significantly reduced, while that of JNK2 and Src/pSrc increased. Compared with micro-TiO2 particles, the nano-TiO2 particles had strong toxicity. Fecal microbiota transplant confirmed the key role of gut microbiota in intestinal toxicity. The levels of gut microbiota-host co-metabolites, including pyroglutamic acid, L-glutamic acid, phenylacetic acid, and 3-hydroxyphenylacetic acid, changed significantly. Significant changes were observed in the glutathione and propanoate metabolic pathways. There was a significant correlation between the changes in gut microbiota, metabolites, and intestinal cytokine levels. These, together with the intestinal barrier damage signaling pathway, constitute the network mechanism of the intestinal toxicity of TiO2 particles.}, }
@article {pmid35073073, year = {2022}, author = {Liu, Y and Huang, W and Zhu, Y and Zhao, T and Xiao, F and Wang, Y and Lu, B}, title = {Acteoside, the Main Bioactive Compound in Osmanthus fragrans Flowers, Palliates Experimental Colitis in Mice by Regulating the Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.1c07583}, pmid = {35073073}, issn = {1520-5118}, abstract = {The present study investigated the effects of Osmanthus fragrans flowers and acteoside on murine colitis and the underlying mechanisms. The O. fragrans flower extract (OFE) and acteoside were administrated to chemically induced colitic mice. The results showed that OFE or acteoside ameliorates intestinal inflammation, oxidative stress, and activation of nuclear factor-κB (NF-κB) in colitic mice. The dysbiosis of the gut microbiome in colitic mice was also partly restored by OFE or acteoside, which was characterized by the alteration of the gut microbiome structure and the enrichment of beneficial bacteria (Akkermansia muciniphila and Bacteroides thetaiotaomicron). Dextran sulfate sodium (DSS)-induced gut metabolome dysfunctions (e.g., sphingosine metabolism and amino acids metabolism) in colitic mice were also partly restored by OFE and acteoside. A fecal microbiota (FM) transplantation study suggested that, compared with the FM from the normal diet-dosed donor mice, the FM from the OFE- or acteoside-dosed donor mice significantly suppressed colitic symptoms.}, }
@article {pmid35069488, year = {2021}, author = {George, S and Aguilera, X and Gallardo, P and Farfán, M and Lucero, Y and Torres, JP and Vidal, R and O'Ryan, M}, title = {Bacterial Gut Microbiota and Infections During Early Childhood.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {793050}, pmid = {35069488}, issn = {1664-302X}, abstract = {Gut microbiota composition during the first years of life is variable, dynamic and influenced by both prenatal and postnatal factors, such as maternal antibiotics administered during labor, delivery mode, maternal diet, breastfeeding, and/or antibiotic consumption during infancy. Furthermore, the microbiota displays bidirectional interactions with infectious agents, either through direct microbiota-microorganism interactions or indirectly through various stimuli of the host immune system. Here we review these interactions during childhood until 5 years of life, focusing on bacterial microbiota, the most common gastrointestinal and respiratory infections and two well characterized gastrointestinal diseases related to dysbiosis (necrotizing enterocolitis and Clostridioides difficile infection). To date, most peer-reviewed studies on the bacterial microbiota in childhood have been cross-sectional and have reported patterns of gut dysbiosis during infections as compared to healthy controls; prospective studies suggest that most children progressively return to a "healthy microbiota status" following infection. Animal models and/or studies focusing on specific preventive and therapeutic interventions, such as probiotic administration and fecal transplantation, support the role of the bacterial gut microbiota in modulating both enteric and respiratory infections. A more in depth understanding of the mechanisms involved in the establishment and maintenance of the early bacterial microbiota, focusing on specific components of the microbiota-immunity-infectious agent axis is necessary in order to better define potential preventive or therapeutic tools against significant infections in children.}, }
@article {pmid35068600, year = {2022}, author = {Zhu, J and Su, J}, title = {Alterations of the Gut Microbiome in Recurrent Malignant Gliomas Patients Received Bevacizumab and Temozolomide Combination Treatment and Temozolomide Monotherapy.}, journal = {Indian journal of microbiology}, volume = {62}, number = {1}, pages = {23-31}, pmid = {35068600}, issn = {0046-8991}, abstract = {This case-control study explored compositions of gut microbiome in recurrent malignant gliomas patients who had received bevacizumab and Temozolomide combination treatment and Temozolomide monotherapy. We investigated gut microbiota communities in feces of 29 recurrent malignant gliomas patients received combination treatment with bevacizumab and Temozolomide (Group 1) and monotherapy with Temozolomide alone (Group 2). We took advantage of the high-throughput Illumina Miseq sequencing technology by targeting the third and fourth hypervariable (V3-V4) regions of the 16S ribosomal RNA (rRNA) gene. We found that the structures and richness of the fecal microbiota in Group 1 were different from Group 2 with LEfSe analysis. The fecal microbiota in both Group 1 and Group 2 were mainly composed by Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. However, Group 1 patients had higher relative abundance of Firmicutes, Bacteroidetes, Actinobacteria and lower relative abundance of Bacteroidetes and Cyanobacteria in their fecal microbiota than that in Group 2 patients. To evaluate bevacizumab involved post-treatment state of the fecal microbiota profile, we used random forest predictive model and ensembled decision trees with an AUC of 0.54. This study confirmed that the gut microbiota was different in recurrent malignant gliomas patients received the combination therapy of bevacizumab and Temozolomide compared with Temozolomide monotherapy. Our discover can help better understand the influence of bevacizumab related treatment on recurrent malignant gliomas patients. Therefore, this finding may also support the potentially therapeutic options for recurrent malignant gliomas patients such as fecal microbiota transplant.
Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-021-00962-2.}, }
@article {pmid35068020, year = {2022}, author = {Feng, Y and Zhang, D and Zhao, Y and Duan, T and Sun, H and Ren, L and Ren, X and Lu, G and Liu, Y and Zhang, Z and Li, Y and Li, H and Jia, A and He, S}, title = {Effect of intestinal microbiota transplantation on cerebral ischemia reperfusion injury in aged mice via inhibition of IL-17.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e14313}, doi = {10.1111/nmo.14313}, pmid = {35068020}, issn = {1365-2982}, support = {2021QN-10//Institutional Foundation of The First Affiliated Hospital of Xi'an Jiaotong University/ ; 81602611//National Natural Science Foundation of China/ ; 2015SF034//Social Development Science and Technology Program of Shaanxi Province/ ; 2019KW-036//Key Research and Development Program of Shaanxi Province/ ; 2019SF023//Key Research and Development Program of Shaanxi Province/ ; 2019SF171//Key Research and Development Program of Shaanxi Province/ ; }, abstract = {OBJECTIVES: This study investigates the effects and mechanisms of intestinal microbiota transplantation on cerebral ischemia reperfusion injury in aged mice.
METHODS: We constructed a middle cerebral artery occlusion model after fecal microbiota transplantation from young C57 mice to aged C57 mice for 30 consecutive days via enema. The neurological deficit score, cerebral infarction volume, fecal flora composition, and IL-17 levels in the colon, brain, and serum were evaluated in young mice, aged mice, and aged mice that received fecal microbiota transplantation. Moreover, we administered rIL-17A through caudal vein injection to verify its effect on cerebral ischemia reperfusion injury in aged mice.
RESULTS: We find that aged mice exhibited larger cerebral infarction volume and more severe neurological deficit than young mice after middle cerebral artery occlusion. Bacteroidetes increased and firmicutes decreased significantly in the feces of aged mice after microbiota transplantation. Furthermore, the transplanted mice showed improved neurological function and reduced infarction volume after middle cerebral artery occlusion compared with the control aged mice. We also find that the neuroprotective effect of the microbiota transplantation was reversed by pre-treatment of rIL-17A.
CONCLUSION: In summary, intestinal microbiota transplantation can alleviate cerebral ischemia reperfusion injury in aged mice by restoring their microbiota environment and inhibiting IL-17 in the gut, serum, and brain tissue.}, }
@article {pmid35064189, year = {2022}, author = {Su, L and Hong, Z and Zhou, T and Jian, Y and Xu, M and Zhang, X and Zhu, X and Wang, J}, title = {Health improvements of type 2 diabetic patients through diet and diet plus fecal microbiota transplantation.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {1152}, pmid = {35064189}, issn = {2045-2322}, abstract = {Type 2 diabetes (T2D) is a major public health problem, and gut microbiota dysbiosis has been implicated in the emergence of T2D in humans. Dietary interventions can indirectly influence the health status of patients with type 2 diabetes through their modulatory effects on the intestinal microbiota. In recent years, fecal microbiota transplantation is becoming familiar as a new medical treatment that can rapidly improve intestinal health. We conducted a 90-day controlled open-label trial to evaluate the health improvement ability of a specially designed diet, and the diet combined with fecal microbiota transplantation (FMT). According to our study, both diet and diet plus FMT treatments showed great potential in controlling blood glucose and blood pressure levels. Sequencing the V4 region of 16S rRNA gene on the Illumina MiniSeq platform revealed a shift of intestinal microbial community in T2D patients, and the changes were also observed in response to the treatments. FMT changed the gut microbiota more quickly than diet. Beneficial bacterium, such as Bifidobacterium, increased along the study and was negatively correlated with blood glucose, blood pressure, blood lipid and BMI. Sulfate-reducing bacteria (SRB), Bilophila and Desulfovibrio, decreased significantly after treatment, showed a positive correlation with blood glucose indices. Thus, the specially designed diet is beneficial to improve blood glucose control in diabetic patients, it also showed the potential to reverse dyslipidemia and dysarteriotony.}, }
@article {pmid35062949, year = {2022}, author = {Yi, M and Zheng, X and Niu, M and Zhu, S and Ge, H and Wu, K}, title = {Combination strategies with PD-1/PD-L1 blockade: current advances and future directions.}, journal = {Molecular cancer}, volume = {21}, number = {1}, pages = {28}, pmid = {35062949}, issn = {1476-4598}, support = {81874120//National Natural Science Foundation of China/ ; 82073370//National Natural Science Foundation of China/ ; }, abstract = {Antibodies targeting programmed cell death protein-1 (PD-1) or its ligand PD-L1 rescue T cells from exhausted status and revive immune response against cancer cells. Based on the immense success in clinical trials, ten α-PD-1 (nivolumab, pembrolizumab, cemiplimab, sintilimab, camrelizumab, toripalimab, tislelizumab, zimberelimab, prolgolimab, and dostarlimab) and three α-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for various types of cancers. Nevertheless, the low response rate of α-PD-1/PD-L1 therapy remains to be resolved. For most cancer patients, PD-1/PD-L1 pathway is not the sole speed-limiting factor of antitumor immunity, and it is insufficient to motivate effective antitumor immune response by blocking PD-1/PD-L1 axis. It has been validated that some combination therapies, including α-PD-1/PD-L1 plus chemotherapy, radiotherapy, angiogenesis inhibitors, targeted therapy, other immune checkpoint inhibitors, agonists of the co-stimulatory molecule, stimulator of interferon genes agonists, fecal microbiota transplantation, epigenetic modulators, or metabolic modulators, have superior antitumor efficacies and higher response rates. Moreover, bifunctional or bispecific antibodies containing α-PD-1/PD-L1 moiety also elicited more potent antitumor activity. These combination strategies simultaneously boost multiple processes in cancer-immunity cycle, remove immunosuppressive brakes, and orchestrate an immunosupportive tumor microenvironment. In this review, we summarized the synergistic antitumor efficacies and mechanisms of α-PD-1/PD-L1 in combination with other therapies. Moreover, we focused on the advances of α-PD-1/PD-L1-based immunomodulatory strategies in clinical studies. Given the heterogeneity across patients and cancer types, individualized combination selection could improve the effects of α-PD-1/PD-L1-based immunomodulatory strategies and relieve treatment resistance.}, }
@article {pmid35061893, year = {2022}, author = {Miltiadous, O and Waters, NR and Andrlova, H and Dai, A and Nguyen, CL and Burgos da Silva, M and Lindner, S and Slingerland, J and Giardina, P and Clurman, A and Armijo, GK and Gomes, AL and Lakkaraja, M and Maslak, PG and Scordo, M and Shouval, R and Staffas, A and O'Reilly, RJ and Taur, Y and Prockop, S and Boelens, JJ and Giralt, S and Perales, MA and Devlin, SM and Peled, JU and Markey, KA and van den Brink, MRM}, title = {Early intestinal microbial features are associated with CD4 T cell recovery after allogeneic hematopoietic transplant.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2021014255}, pmid = {35061893}, issn = {1528-0020}, abstract = {Low intestinal microbial diversity is associated with poor outcomes after allogeneic hematopoietic cell transplantation (HCT). Using 16S rRNA sequencing of 2,067 stool samples and flow-cytometry data from 2,370 peripheral blood samples drawn from 894 allogeneic HCT patients, we have linked features of the early post-HCT microbiome with subsequent immune cell recovery. We examined lymphocyte recovery and microbiota features in recipients of both unmodified and CD34-selected allografts. We observed that fecal microbial diversity was an independent predictor of CD4 T cell count 3 months after HCT in recipients of a CD34-selected allograft, who are dependent on de novo lymphopoiesis for their immune recovery. In multivariate models using clinical factors and microbiota features, we consistently observed that increased fecal relative abundance of genus Staphylococcus during the early post-transplant period was associated with worse CD4 T cell recovery. Our observations suggest that the intestinal bacteria - or the factors they produce - can affect early lymphopoiesis and the homeostasis of allograft-derived T cells after transplantation.}, }
@article {pmid35060914, year = {2022}, author = {Chinna Meyyappan, A and Forth, E and Milev, R}, title = {Microbial Ecosystem Therapeutic-2 Intervention in People With Major Depressive Disorder and Generalized Anxiety Disorder: Phase 1, Open-Label Study.}, journal = {Interactive journal of medical research}, volume = {11}, number = {1}, pages = {e32234}, doi = {10.2196/32234}, pmid = {35060914}, issn = {1929-073X}, abstract = {BACKGROUND: Recent studies have investigated the potential of treatments that modify the gut microbiome, such as fecal microbiota transplantation and probiotics, in individuals with psychiatric illnesses.
OBJECTIVE: The aim of this study was to investigate the safety, tolerability, and efficacy of a novel gut microbiome therapeutic, Microbial Ecosystem Therapuetic-2 (MET-2), in people with depression and anxiety.
METHODS: In this phase 1, open-label trial, 12 adults diagnosed with major depressive disorder, generalized anxiety disorder, or both were recruited. Over 8 weeks, participants consumed three capsules per day, orally, of an encapsulated microbial therapeutic (MET-2), which contained 40 strains of bacteria that were purified and lab-grown from the stool of a single healthy donor. Participants were assessed biweekly using clinical scales and questionnaires in order to evaluate the safety, efficacy, and tolerability of the therapeutic.
RESULTS: The therapeutic was found to be generally safe and tolerable, with limited adverse events and side effects and no serious adverse events. Of the 12 individuals included in this study, 9 (75%) responded to treatment (50% improvement in Montgomery-Asberg Depression Rating Scale [MADRS] scores, 7-item Generalized Anxiety Disorder scale [GAD-7] scores, or both, from baseline to the week-8 visit). Over the course of 10 weeks, MET-2 significantly decreased mean MADRS and GAD-7 scores (MADRS: F2.731, 30.05=8.784, P<.001; GAD-7: F2.778, 30.55= 9.638, P<.001). Multiple comparisons with Bonferroni adjustments showed a significant reduction in MADRS scores from baseline (mean 19.00, SD 4.843) to week 6 (mean 11.25, SD 8.001; P=.009), week 8 (mean 8.667, SD 8.732; P=.002), and week 10 (mean 8.250, SD 9.304; P=.006). Multiple comparisons showed a significant reduction in GAD-7 scores from baseline (mean 13.58, SD 4.010) to week 4 (mean 9.167, SD 5.096; P=.03), week 6 (mean 7.667, SD 4.539; P=.004), week 8 (mean 7.333, SD 6.583; P=.03), and week 10 (mean 7.500, SD 6.448; P=.03).
CONCLUSIONS: The findings from this study are the first to provide evidence for the role of microbial ecosystem therapy in treating depression and anxiety. However, a double-blind, randomized controlled trial with a larger sample size is needed for more conclusive results.
TRIAL REGISTRATION: ClinicalTrials.gov NCT04052451; https://www.clinicaltrials.gov/ct2/show/NCT04052451.
RR2-10.2196/17223.}, }
@article {pmid35060521, year = {2022}, author = {Li, J and Wang, D and Sun, J}, title = {Application of fecal microbial transplantation in hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.}, journal = {Medicine}, volume = {101}, number = {3}, pages = {e28584}, doi = {10.1097/MD.0000000000028584}, pmid = {35060521}, issn = {1536-5964}, support = {CYFY2017GLPXH002//the State Key Clinical Specially Construction Project, number CYFY2017GLPXH002/ ; }, abstract = {RATIONALE: Transjugular intrahepatic portosystemic shunt (TIPS) is mainly used to treat acute and chronic esophageal, gastric, and intestinal variceal bleeding and refractory ascites caused by portal hypertension. The most common complication of TIPS is the development of hepatic encephalopathy (HE). Fecal microbiota transplantation (FMT) is an emerging method for treating diseases by altering the intestinal flora. We present 2 cases of FMT that ameliorated liver function and HE after TIPS.
PATIENT CONCERNS: In this report, 2 patients with liver cirrhosis secondary to hepatitis B had recurrent Grade 2-3 HE after TIPS.
DIAGNOSIS: Two patients were diagnosed as having HE.
INTERVENTIONS: The 2 patients separately received 3 times of FMT.
OUTCOMES: The liver function of both patients improved, the clinical symptoms were relieved, and the number of HE attacks decreased significantly after FMT.
LESSONS: FMT may be another effective way to treat HE, and is worthy of further research.}, }
@article {pmid35059329, year = {2021}, author = {Zuppi, M and Hendrickson, HL and O'Sullivan, JM and Vatanen, T}, title = {Phages in the Gut Ecosystem.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {822562}, pmid = {35059329}, issn = {2235-2988}, abstract = {Phages, short for bacteriophages, are viruses that specifically infect bacteria and are the most abundant biological entities on earth found in every explored environment, from the deep sea to the Sahara Desert. Phages are abundant within the human biome and are gaining increasing recognition as potential modulators of the gut ecosystem. For example, they have been connected to gastrointestinal diseases and the treatment efficacy of Fecal Microbiota Transplant. The ability of phages to modulate the human gut microbiome has been attributed to the predation of bacteria or the promotion of bacterial survival by the transfer of genes that enhance bacterial fitness upon infection. In addition, phages have been shown to interact with the human immune system with variable outcomes. Despite the increasing evidence supporting the importance of phages in the gut ecosystem, the extent of their influence on the shape of the gut ecosystem is yet to be fully understood. Here, we discuss evidence for phage modulation of the gut microbiome, postulating that phages are pivotal contributors to the gut ecosystem dynamics. We therefore propose novel research questions to further elucidate the role(s) that they have within the human ecosystem and its impact on our health and well-being.}, }
@article {pmid35058749, year = {2021}, author = {Hua, D and Li, S and Li, S and Wang, X and Wang, Y and Xie, Z and Zhao, Y and Zhang, J and Luo, A}, title = {Gut Microbiome and Plasma Metabolome Signatures in Middle-Aged Mice With Cognitive Dysfunction Induced by Chronic Neuropathic Pain.}, journal = {Frontiers in molecular neuroscience}, volume = {14}, number = {}, pages = {806700}, pmid = {35058749}, issn = {1662-5099}, abstract = {Patients with chronic neuropathic pain (CNP) often complain about their terrible memory, especially the speed of information processing. Accumulating evidence suggests a possible link between gut microbiota and pain processing as well as cognitive function via the microbiota-gut-brain axis. This study aimed at exploring the fecal microbiome and plasma metabolite profiles in middle-aged spared nerve injury (SNI) mice model with cognitive dysfunction (CD) induced by CNP. The hierarchical cluster analysis of performance in the Morris water maze test was used to classify SNI mice with CD or without CD [i.e., non-CD (NCD)] phenotype. 16S rRNA sequencing revealed a lower diversity of gut bacteria in SNI mice, and the increase of Actinobacteria, Proteus, and Bifidobacterium might contribute to the cognitive impairment in the CNP condition. The plasma metabolome analysis showed that the endocannabinoid (eCB) system, disturbances of lipids, and amino acid metabolism might be the dominant signatures of CD mice. The fecal microbiota transplantation of the Sham (not CD) group improved allodynia and cognitive performance in pseudo-germ-free mice via normalizing the mRNA expression of eCB receptors, such as cn1r, cn2r, and htr1a, reflecting the effects of gut bacteria on metabolic activity. Collectively, the findings of this study suggest that the modulation of gut microbiota and eCB signaling may serve as therapeutic targets for cognitive deficits in patients with CNP.}, }
@article {pmid35058059, year = {2022}, author = {Prado, C and Abatti, MR and Michels, M and Córneo, E and Cucker, L and Borges, H and Dias, R and Rocha, LB and Dal-Pizzol, F and Ritter, C}, title = {Comparative effects of fresh and sterile fecal microbiota transplantation in an experimental animal model of necrotizing enterocolitis.}, journal = {Journal of pediatric surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jpedsurg.2021.12.013}, pmid = {35058059}, issn = {1531-5037}, abstract = {INTRODUCTION: Necrotizing Enterocolitis (NEC) is a serious intestinal disease that affects premature neonates, causing high mortality, despite the technological development in neonatal intensive care, with antibiotics, parenteral nutrition, surgery, and advanced life support. The correction of dysbiosis with fecal microbiome transplantation (FMT) has shown beneficial effects in experimental models of the disease. The different forms of administration and conservation of FMT and mixed results depending on several factors lead to questions about the mechanism of action of FMT. This study aimed to compare the effectiveness of fresh, sterile FMT and probiotic treatment under parameters of inflammation, oxidative stress, and tissue damage in a neonatal model of NEC.
METHODS: One-day-old Wistar rats were used to induce NEC model. Animals were divided in five groups: Control + saline; NEC + saline; NEC + fresh FMT; NEC + sterile FMT and NEC+ probiotics. Parameters of inflammatory response and oxidative damage were measured in the gut, brain, and serum. It was also determined gut histopathological alterations.
RESULTS: Proinflammatory cytokines were increased in the NEC group, and IL-10 levels decreased in the gut, brain, and serum. Fresh and sterile FMT decreased inflammation when compared to the use of probiotics. Oxidative and histological damage to the intestine was apparent in the NEC group, and both FMT treatments had a protective effect.
CONCLUSION: Fresh and sterile FMT effectively reduced the inflammatory response, oxidative damage, and histological alterations in the gut and brain compared to an experimental NEC model.}, }
@article {pmid35057693, year = {2022}, author = {Jena, A and Mishra, S and Singh, AK and Sekar, A and Sharma, V}, title = {Cytomegalovirus in ulcerative colitis: An evidence-based approach to diagnosis and treatment.}, journal = {Expert review of gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1080/17474124.2022.2032662}, pmid = {35057693}, issn = {1747-4132}, abstract = {INTRODUCTION: The detection of cytomegalovirus (CMV) in setting of inflammatory bowel disease often creates confusion whether CMV is a 'bystander' or 'disease'.
AREAS COVERED: : This review discusses the clinical conundrum of CMV in ulcerative colitis, approach to discriminate infection from disease, and therapeutic considerations (immunosuppressive and anti-CMV treatment). CMV disease should be considered in corticosteroid refractory/ dependent and thiopurine refractory disease. Endoscopy may reveal deep punched out ulcers, irregular ulcers or cobble-stoning. The diagnosis rests on the presence and abundance of viral inclusion bodies on hematoxylin and eosin stain, positive immunohistochemistry and/or positive tissue polymerase chain reaction. CMV disease is associated with worse outcomes including increased colectomy rates.
EXPERT OPINION: : The timing and duration of antiviral drugs in CMV disease is debatable but depends on the load of CMV in tissue. In high grade infection, CMV needs to be treated while increasing immunosuppression may work in setting of low-grade infection. Ganciclovir is the drug of choice for treatment of CMV disease. Tumor necrosis factor inhibitors may be useful for treating underlying disease activity in the setting of CMV. Other emerging therapies include fecal microbiota transplantation. Randomized studies are necessary to define the best timing and duration of anti-CMV therapy.}, }
@article {pmid35056472, year = {2021}, author = {Masucci, L and Quaranta, G}, title = {Fecal Microbiota Transplantation: What's New?.}, journal = {Microorganisms}, volume = {10}, number = {1}, pages = {}, doi = {10.3390/microorganisms10010023}, pmid = {35056472}, issn = {2076-2607}, abstract = {The gut microbiota is composed of trillions of different microorganisms: bacteria, archaea, phages and protozoa, which represent a real solid organ, with an approximate weight of 2 kg [...].}, }
@article {pmid35056392, year = {2022}, author = {Tkach, S and Dorofeyev, A and Kuzenko, I and Boyko, N and Falalyeyeva, T and Boccuto, L and Scarpellini, E and Kobyliak, N and Abenavoli, L}, title = {Current Status and Future Therapeutic Options for Fecal Microbiota Transplantation.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {1}, pages = {}, doi = {10.3390/medicina58010084}, pmid = {35056392}, issn = {1648-9144}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, abstract = {The intestinal microbiota plays an important role in maintaining human health, and its alteration is now associated with the development of various gastrointestinal (ulcerative colitis, irritable bowel syndrome, constipation, etc.) and extraintestinal diseases, such as cancer, metabolic syndrome, neuropsychiatric diseases. In this context, it is not surprising that gut microbiota modification methods may constitute a therapy whose potential has not yet been fully investigated. In this regard, the most interesting method is thought to be fecal microbiota transplantation, which consists of the simultaneous replacement of the intestinal microbiota of a sick recipient with fecal material from a healthy donor. This review summarizes the most interesting findings on the application of fecal microbiota transplantation in gastrointestinal and extraintestinal pathologies.}, }
@article {pmid35054136, year = {2022}, author = {Herman, A and Herman, AP}, title = {Could Candida Overgrowth Be Involved in the Pathophysiology of Autism?.}, journal = {Journal of clinical medicine}, volume = {11}, number = {2}, pages = {}, doi = {10.3390/jcm11020442}, pmid = {35054136}, issn = {2077-0383}, abstract = {The purpose of this review is to summarize the current acquiredknowledge of Candida overgrowth in the intestine as a possible etiology of autism spectrum disorder (ASD). The influence of Candida sp. on the immune system, brain, and behavior of children with ASD isdescribed. The benefits of interventions such as a carbohydrates-exclusion diet, probiotic supplementation, antifungal agents, fecal microbiota transplantation (FMT), and microbiota transfer therapy (MTT) will be also discussed. Our literature query showed that the results of most studies do not fully support the hypothesis that Candida overgrowth is correlated with gastrointestinal (GI) problems and contributes to autism behavioral symptoms occurrence. On the one hand, it was reported that the modulation of microbiota composition in the gut may decrease Candida overgrowth, help reduce GI problems and autism symptoms. On the other hand, studies on humans suggesting the beneficial effects of a sugar-free diet, probiotic supplementation, FMT and MTT treatment in ASD are limited and inconclusive. Due to the increasing prevalence of ASD, studies on the etiology of this disorder are extremely needed and valuable. However, to elucidate the possible involvement of Candida in the pathophysiology of ASD, more reliable and well-designed research is certainly required.}, }
@article {pmid35053205, year = {2021}, author = {Vallianou, N and Christodoulatos, GS and Karampela, I and Tsilingiris, D and Magkos, F and Stratigou, T and Kounatidis, D and Dalamaga, M}, title = {Understanding the Role of the Gut Microbiome and Microbial Metabolites in Non-Alcoholic Fatty Liver Disease: Current Evidence and Perspectives.}, journal = {Biomolecules}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/biom12010056}, pmid = {35053205}, issn = {2218-273X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD begins as a relatively benign hepatic steatosis which can evolve to non-alcoholic steatohepatitis (NASH); the risk of cirrhosis and hepatocellular carcinoma (HCC) increases when fibrosis is present. NAFLD represents a complex process implicating numerous factors-genetic, metabolic, and dietary-intertwined in a multi-hit etiopathogenetic model. Recent data have highlighted the role of gut dysbiosis, which may render the bowel more permeable, leading to increased free fatty acid absorption, bacterial migration, and a parallel release of toxic bacterial products, lipopolysaccharide (LPS), and proinflammatory cytokines that initiate and sustain inflammation. Although gut dysbiosis is present in each disease stage, there is currently no single microbial signature to distinguish or predict which patients will evolve from NAFLD to NASH and HCC. Using 16S rRNA sequencing, the majority of patients with NAFLD/NASH exhibit increased numbers of Bacteroidetes and differences in the presence of Firmicutes, resulting in a decreased F/B ratio in most studies. They also present an increased proportion of species belonging to Clostridium, Anaerobacter, Streptococcus, Escherichia, and Lactobacillus, whereas Oscillibacter, Flavonifaractor, Odoribacter, and Alistipes spp. are less prominent. In comparison to healthy controls, patients with NASH show a higher abundance of Proteobacteria, Enterobacteriaceae, and Escherichia spp., while Faecalibacterium prausnitzii and Akkermansia muciniphila are diminished. Children with NAFLD/NASH have a decreased proportion of Oscillospira spp. accompanied by an elevated proportion of Dorea, Blautia, Prevotella copri, and Ruminococcus spp. Gut microbiota composition may vary between population groups and different stages of NAFLD, making any conclusive or causative claims about gut microbiota profiles in NAFLD patients challenging. Moreover, various metabolites may be involved in the pathogenesis of NAFLD, such as short-chain fatty acids, lipopolysaccharide, bile acids, choline and trimethylamine-N-oxide, and ammonia. In this review, we summarize the role of the gut microbiome and metabolites in NAFLD pathogenesis, and we discuss potential preventive and therapeutic interventions related to the gut microbiome, such as the administration of probiotics, prebiotics, synbiotics, antibiotics, and bacteriophages, as well as the contribution of bariatric surgery and fecal microbiota transplantation in the therapeutic armamentarium against NAFLD. Larger and longer-term prospective studies, including well-defined cohorts as well as a multi-omics approach, are required to better identify the associations between the gut microbiome, microbial metabolites, and NAFLD occurrence and progression.}, }
@article {pmid34871192, year = {2022}, author = {Buckley, AM and Moura, IB and Wilcox, MH}, title = {The potential of microbiome replacement therapies for Clostridium difficile infection.}, journal = {Current opinion in gastroenterology}, volume = {38}, number = {1}, pages = {1-6}, pmid = {34871192}, issn = {1531-7056}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; }, abstract = {PURPOSE OF REVIEW: There is a paradox when treating Clostridium difficile infection (CDI); treatment antibiotics reduce C. difficile colonization but cause further microbiota disruption and can lead to recurrent disease. The success of faecal microbiota transplants (FMT) in treating CDI has become a new research area in microbiome restorative therapies but are they a viable long-term treatment option?
RECENT FINDINGS: C. difficile displays metabolic flexibility to use different nutritional sources during CDI. Using microbiome therapies for the efficient restoration of bile homeostasis and to reduce the bioavailability of preferential nutrients will target the germination ability of C. difficile spores and the growth rate of vegetative cells. Several biotechnology companies have developed microbiome therapeutics for treating CDI, which are undergoing clinical trials.
SUMMARY: There is confidence in using restorative microbiome therapies for treating CDI after the demonstrated efficacy of FMT, where several biotechnology companies are aiming to supply what would be a 'first in class' treatment option. Efficient removal of C. difficile from the different intestinal biogeographies should be considered in future microbiome therapies. With the gut microbiota implicated in different diseases, more work is needed to assess the long-term consequences of microbiome therapies.}, }
@article {pmid34863330, year = {2022}, author = {Haifer, C and Paramsothy, S and Kaakoush, NO and Saikal, A and Ghaly, S and Yang, T and Luu, LDW and Borody, TJ and Leong, RW}, title = {Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {7}, number = {2}, pages = {141-151}, doi = {10.1016/S2468-1253(21)00400-3}, pmid = {34863330}, issn = {2468-1253}, mesh = {Administration, Oral ; Adult ; Anti-Bacterial Agents/therapeutic use ; Colitis, Ulcerative/pathology/*therapy ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Female ; Freeze Drying ; Humans ; Male ; Middle Aged ; Remission Induction ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) delivered via colonoscopic infusion or enemas have been shown to induce remission in a proportion of patients with active ulcerative colitis. Whether orally administered FMT is effective in ulcerative colitis is unknown. We aimed to assess the efficacy of oral lyophilised FMT for the treatment of active ulcerative colitis.
METHODS: A double-blind, randomised, placebo-controlled trial was conducted at two centres in Australia. Eligible patients were aged 18-75 years with active ulcerative colitis (defined as clinical and endoscopic active ulcerative colitis, with a total Mayo score of 4-10, and a Mayo endoscopic subscore ≥1). After 2 weeks of amoxicillin, metronidazole, and doxycycline, patients were randomly assigned in a 1:1 ratio to receive either oral lyophilised FMT or placebo capsules for 8 weeks, using a prespecified computer-generated randomisation list with a permuted block size of 8. The primary outcome was corticosteroid-free clinical remission with endoscopic remission or response (total Mayo score ≤2, all subscores ≤1, and ≥1 point reduction in endoscopic subscore) at week 8. At week 8, FMT responders were randomly assigned (in a 1:1 ratio, permuted block size of 8) to either continue or withdraw FMT for a further 48 weeks. Analyses were done by modified intention-to-treat, including all patients who received at least one study dose. This trial is registered with Australian New Zealand Trial Registry, number ACTRN 12619000611123; this is the final report of the trial.
FINDINGS: Between May 20, 2019, and March 24, 2020, 35 patients were randomly assigned: 15 to receive FMT and 20 to receive placebo. Recruitment was terminated early due to the COVID-19 pandemic. At week 8, eight (53%) of 15 patients in the FMT group were in corticosteroid-free clinical remission with endoscopic remission or response, as were three (15%) of 20 patients in the placebo group (difference 38·3%, 95% CI 8·6-68·0; p=0·027; odds ratio 5·0, 95% CI 1·8-14·1). Adverse events occurred in 10 (67%) patients in the FMT group and 17 (85%) of those in the placebo group during the 8-week induction period, and were generally mild and self-limiting gastrointestinal complaints. Serious adverse events included worsening ulcerative colitis (two in the FMT group, one in the placebo group) and per-rectal bleeding (one in the placebo group). Ten patients in the FMT group who achieved a clinical or endoscopic response entered the maintenance phase and were randomly assigned to continue open-label FMT (n=4) or withdraw therapy (n=6). All four (100%) patients who continued FMT were in clinical, endoscopic, and histologic remission at week 56 compared with none of the patients who had FMT withdrawn.
INTERPRETATION: Antibiotics followed by orally administered FMT was associated with the induction of remission in patients with active ulcerative colitis. Continuing FMT was well tolerated and appeared to demonstrate clinical, endoscopic, and histological efficacy. Oral FMT could be a promising and feasible treatment option for patients with ulcerative colitis.
FUNDING: St Vincent's Clinic Foundation, Gastroenterological Society of Australia, Gutsy Group.}, }
@article {pmid34750433, year = {2021}, author = {Knudsen, JK and Michaelsen, TY and Bundgaard-Nielsen, C and Nielsen, RE and Hjerrild, S and Leutscher, P and Wegener, G and Sørensen, S}, title = {Faecal microbiota transplantation from patients with depression or healthy individuals into rats modulates mood-related behaviour.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {21869}, pmid = {34750433}, issn = {2045-2322}, mesh = {Adult ; Affect ; Animals ; Behavior, Animal ; Depression/genetics/psychology/*therapy ; Disease Models, Animal ; *Fecal Microbiota Transplantation/psychology ; Female ; Gene Expression ; Humans ; Male ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Rats ; Tight Junction Proteins/genetics ; Young Adult ; }, abstract = {Differences in gut microbiota composition have been observed in patients with major depressive disorder (MDD) compared to healthy individuals. Here, we investigated if faecal microbiota transplantation (FMT) from patients with MDD into rats could induce a depressive-like phenotype. We performed FMT from patients with MDD (FMT-MDD) and healthy individuals (FMT-Healthy) into male Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats and assessed depressive-like behaviour. No behavioural differences were observed in the FSL rats. In FRL rats, the FMT-Healthy group displayed significantly less depressive-like behaviour than the FMT-MDD group. However, there was no difference in behaviour between FMT-MDD FRL rats and negative controls, indicating that FMT-Healthy FRL rats received beneficial bacteria. We additionally found different taxa between the FMT-MDD and the FMT-Healthy FRL rats, which could be traced to the donors. Four taxa, three belonging to the family Ruminococcaceae and the genus Lachnospira, were significantly elevated in relative abundance in FMT-MDD rats, while the genus Coprococcus was depleted. In this study, the FMT-MDD group was different from the FMT-Healthy group based on behaviour and intestinal taxa.}, }
@article {pmid34636363, year = {2022}, author = {Bilsen, MP and Lambregts, MMC and van Prehn, J and Kuijper, EJ}, title = {Faecal microbiota replacement to eradicate antimicrobial resistant bacteria in the intestinal tract - a systematic review.}, journal = {Current opinion in gastroenterology}, volume = {38}, number = {1}, pages = {15-25}, pmid = {34636363}, issn = {1531-7056}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacteria ; *Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; }, abstract = {PURPOSE OF REVIEW: Antimicrobial resistance is a rising threat to global health and is associated with increased mortality. Intestinal colonisation with multidrug-resistant organisms (MDRO) can precede invasive infection and facilitates spread within communities and hospitals. Novel decolonisation strategies, such as faecal microbiota transplantation (FMT), are being explored. The purpose of this review is to provide an update on how the field of FMT for MDRO decolonisation has developed during the past year and to assess the efficacy of FMT for intestinal MDRO decolonisation.
RECENT FINDINGS: Since 2020, seven highly heterogenous, small, nonrandomised cohort studies and five case reports have been published. In line with previous literature, decolonisation rates ranged from 20 to 90% between studies and were slightly higher for carbapenem-resistant Enterobacteriaceae than vancomycin-resistant Enterococcus. Despite moderate decolonisation rates in two studies, a reduction in MDRO bloodstream and urinary tract infections was observed.
SUMMARY AND IMPLICATIONS: Although a number of smaller cohort studies show some effect of FMT for MDRO decolonisation, questions remain regarding the true efficacy of FMT (taking spontaneous decolonisation into account), the optimal route of administration, the role of antibiotics pre and post-FMT and the efficacy in different patient populations. The observed decrease in MDRO infections post-FMT warrants further research.}, }
@article {pmid35050941, year = {2022}, author = {Beran, A and Sharma, S and Ghazaleh, S and Lee-Smith, W and Aziz, M and Kamal, F and Acharya, A and Adler, DG}, title = {Predictors of Fecal Microbiota Transplant Failure in Clostridioides difficile Infection: An Updated Meta-analysis.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001667}, pmid = {35050941}, issn = {1539-2031}, abstract = {INTRODUCTION AND AIM: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent/refractory Clostridioides difficile infection (CDI) with a 10% to 20% risk of recurrence after a single FMT. In this meta-analysis, we aimed to evaluate the predictors of FMT failure.
METHODS: A comprehensive search of MEDLINE, Embase, Cochrane, and Web of Science databases through July 2021 was performed. All studies that evaluated risk factors associated with FMT failure in a multivariate model were included. We calculated pooled odds ratios with 95% confidence intervals for risk factors reported in ≥3 studies using a random-effects model.
RESULTS: Twenty studies involving 4327 patients (63.6% females) with recurrent/refractory CDI who underwent FMT were included. FMT failed in 705 patients (16.3%) with 2 to 3 months of follow-up in most studies. A total of 12 different risk factors were reported in a multivariate model in ≥3 studies. Meta-analysis showed that advanced age, severe CDI, inflammatory bowel disease, peri-FMT use of non-CDI antibiotics, prior CDI-related hospitalizations, inpatient status, and poor quality of bowel preparation were significant predictors of FMT failure. Charlson Comorbidity Index, female gender, immunosuppressed status, patient-directed donor, and number of CDI recurrences were not associated with FMT failure.
CONCLUSIONS: Adequate bowel preparation at the time of FMT and optimizing antibiotic stewardship practices in the peri-FMT period can improve the success of FMT. Patients with nonmodifiable risk factors should be counseled about the risk of FMT failure. Our results may help develop a risk stratification model to predict FMT failure in CDI patients.}, }
@article {pmid35046924, year = {2021}, author = {Qiao, Y and Zhang, Z and Zhai, Y and Yan, X and Zhou, W and Liu, H and Guan, L and Peng, L}, title = {Apigenin Alleviates Obesity-Associated Metabolic Syndrome by Regulating the Composition of the Gut Microbiome.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {805827}, doi = {10.3389/fmicb.2021.805827}, pmid = {35046924}, issn = {1664-302X}, abstract = {The gut microbiota, often viewed as a "digestive organ," can influence the development of obesity and related metabolic disorders. Diet is significantly important in shaping the structure and modulating the function of the gut microbiota. Apigenin (Api) widely exists in fruits and vegetables as a naturally occurring flavonoid and has anti-obesogenic, anti-inflammatory, and anti-carcinogenic properties. Its low bioavailability means it has enough time to interact with the intestine thus becomes a potential substrate for the gut intestine; thus, contributing to gut health. Here, we show that Api reduces whole-body weight, low-grade inflammation, and insulin resistance in high-fat diet (HFD)-induced obese mice. Our results reflect that Api supplementation can substantially improve intestinal dysbiosis triggered by HFD and restores gut barrier damage by alleviating metabolic endotoxemia. Augmentation of Akkermansia and Incertae_Sedis along with reduction of Faecalibaculum and Dubosiella at the genus level potentially mediated the protective effects of Api on metabolic syndrome. Furthermore, we show that the impact of Api on the reduction of body weight and the modification of gut microbiota could be transferred from Api-administered mice to HFD-feeding mice via horizontal fecal microbiota transplantation. Taken together, our data highlight the prebiotic role of Api and show its contribution to the restraint of gut dysbiosis and metabolic deterioration associated with obesity in mice.}, }
@article {pmid35045605, year = {2022}, author = {Kang, SH and Gweon, TG and Hwang, H and Baeg, MK}, title = {A Case of Ischemic Colitis Complicated by Clostridioides Difficile Infection Treated with Fecal Microbiota Transplantation.}, journal = {Clinical endoscopy}, volume = {}, number = {}, pages = {}, doi = {10.5946/ce.2021.199}, pmid = {35045605}, issn = {2234-2400}, abstract = {Ischemic colitis is an inflammatory condition of the colon that results from insufficient blood supply commonly caused by enterocolitis, vessel occlusion, or shock. In contrast, pseudomembranous colitis is a clinical manifestation of Clostridioides difficile infection (CDI). Ischemic colitis caused by CDI has rarely been reported. Fecal microbiota transplantation (FMT) is an efficient treatment for refractory or fulminant CDI, and the indications for its use have recently expanded. However, performing FMT in patients with ischemic colitis is challenging because of the risk of perforation. Here, we have presented a case of ischemic colitis caused by CDI that was successfully treated with FMT via sigmoidoscopy.}, }
@article {pmid33798737, year = {2021}, author = {Li, X and Khan, I and Xia, W and Huang, G and Liu, L and Law, BYK and Yin, L and Liao, W and Leong, W and Han, R and Wong, VKW and Xia, C and Guo, X and Hsiao, WLW}, title = {Icariin enhances youth-like features by attenuating the declined gut microbiota in the aged mice.}, journal = {Pharmacological research}, volume = {168}, number = {}, pages = {105587}, doi = {10.1016/j.phrs.2021.105587}, pmid = {33798737}, issn = {1096-1186}, mesh = {Aging/*drug effects ; Animals ; Fecal Microbiota Transplantation ; Flavonoids/*pharmacology ; Gastrointestinal Microbiome/*drug effects/physiology ; Goblet Cells/drug effects ; Intestines/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Tight Junctions/drug effects ; }, abstract = {We previously reported the neuroprotective effects of icariin in rat cortical neurons. Here, we present a study on icariin's anti-aging effect in 24-month aged mice by treating them with a single daily dose of 100 mg/kg of icariin for 15 consecutive days. Icariin treatment improved motor coordination and learning skills while lowered oxidative stress biomarkers in the serum, brain, kidney, and liver of the aged mice. In addition, icariin improved the intestinal integrity of the aged mice by upregulating tight junction adhesion molecules and the Paneth and goblet cells, along with the reduction of iNOS and pro-inflammatory cytokines (IL-1β, TNF-α, IL-2 and IL-6, and IL-12). Icariin treatments also significantly upregulated aging-related signaling molecules, Sirt 1, 3 & 6, Pot1α, BUB1b, FOXO1, Ep300, ANXA3, Calb1, SNAP25, and BDNF in old mice. Through gut microbiota (GM) analysis, we observed icariin-associated improvements in GM composition of aged mice by reinstating bacteria found in the young mice, while suppressing some bacteria found in the untreated old mice. To clarify whether icariin's anti-aging effect is rooted in the GM, we performed fecal microbiota transfer (FMT) from icariin-treated old mice to the old mice. FMT-recipients exhibited similar improvements in the rotarod score and age-related biomarkers as observed in the icariin-treated old mice. Equal or better improvement on the youth-like features was noticed when aged mice were FMT with feces from young mice. Our study shows that both direct treatments with icariin and fecal transplant from the icariin-treated aged mice produce similar anti-aging phenotypes in the aged mice. We prove that GM plays a pivotal role in the healing abilities of icariin. Icariin has the potentials to be developed as a medicine for the wellness of the aged adults.}, }
@article {pmid35045306, year = {2022}, author = {Huang, G and Wang, L and Li, J and Hou, R and Wang, M and Wang, Z and Qu, Q and Zhou, W and Nie, Y and Hu, Y and Ma, Y and Yan, L and Wei, H and Wei, F}, title = {Seasonal shift of the gut microbiome synchronizes host peripheral circadian rhythm for physiological adaptation to a low-fat diet in the giant panda.}, journal = {Cell reports}, volume = {38}, number = {3}, pages = {110203}, doi = {10.1016/j.celrep.2021.110203}, pmid = {35045306}, issn = {2211-1247}, abstract = {Characteristics of the gut microbiome vary synchronously with changes in host diet. However, the underlying effects of these fluctuations remain unclear. Here, we performed fecal microbiota transplantation (FMT) of diet-specific feces from an endangered mammal (the giant panda) into a germ-free mouse model. We demonstrated that the butyrate-producing bacterium Clostridium butyricum was more abundant during shoot-eating season than during the leaf-eating season, congruent with the significant increase in host body mass. Following season-specific FMT, the microbiota of the mouse model resembled that of the donor, and mice transplanted with the microbiota from the shoot-eating season grew faster and stored more fat. Mechanistic investigations revealed that butyrate extended the upregulation of hepatic circadian gene Per2, subsequently increasing phospholipid biosynthesis. Validation experiments further confirmed this causal relationship. This study demonstrated that seasonal shifts in the gut microbiome affect growth performance, facilitating a deeper understanding of host-microbe interactions in wild mammals.}, }
@article {pmid35040380, year = {2022}, author = {Wang, Y and Cui, B and Zhang, F}, title = {Refractory ulcerative colitis stabilized by interval washed microbiota transplantation: less is more.}, journal = {Current medical research and opinion}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/03007995.2022.2030563}, pmid = {35040380}, issn = {1473-4877}, abstract = {Ulcerative colitis (UC) is an autoimmune inflammatory disorder characterized by a relapsing and remitting course. The gut microbiota is implicated in the pathogenesis of UC. Fecal microbiota transplant (FMT) has been reported as a rescue therapy for refractory UC. The newly improved methodology of FMT was recently coined as washed microbiota transplantation (WMT) based on the automatic purification system and washing process. Colonic transendoscopic enteral tubing (TET) is a novel delivery of WMT within the whole colon. In this case, the patient with refractory UC underwent two different strategies of fresh FMT. The prior strategy conducted daily FMT through the percutaneous endoscopic cecostomy (PEC) tube for 60 days. The latter performed WMT every 3-35 months by colonic TET or gastroscopy. The patient was effectively responsive to both strategies. The repeated interval WMTs induced the long-term clinical remission for the patient. The case encouraged the physicians to consider repeated interval WMTs into practice as a long-term treatment strategy for refractory UC. Moreover, we hope more physicians and researchers would be inspired to study clinical strategies, such as optimizing the frequency and interval of WMTs and the related delivering strategy.}, }
@article {pmid35040302, year = {2021}, author = {Larussa, T and Abenavoli, L and Fabiano, G and Mancuso, MA and Polimeni, N and Dumitrascu, DL and Luzza, F}, title = {Gut microbiota in inflammatory bowel disease: a target for therapy not to be missed.}, journal = {Minerva gastroenterology}, volume = {67}, number = {4}, pages = {357-368}, doi = {10.23736/S2724-5985.21.02907-7}, pmid = {35040302}, issn = {2724-5365}, abstract = {In the last years, the gut microbiota achieved great importance, since several studies demonstrated its correlation with the immune system and with the maintenance of intestinal homeostasis, as well as with the regulation of the integrity of the epithelium and the intestinal motility. An imbalance in microbial species promotes a dysbiosis, which has been associated with chronic diseases such as metabolic syndrome, inflammatory diseases, and some behavior disorders. The association with gut microbiota and dysbiosis has been demonstrated mostly in inflammatory bowel disease (IBD). Several studies investigated the application of antibiotics, prebiotics, probiotics, and fecal microbiota transplantation in the treatment strategies for IBD. In this review, we discuss the recent findings on the potential role of the gut microbiota manipulation, with particular attention to bacterial microbiota, which could be implicated for a successful IBD therapeutic approach.}, }
@article {pmid35037353, year = {2022}, author = {Benech, N and Legendre, P and Radoszycki, L and Varriale, P and Sokol, H}, title = {Patient knowledge of gut microbiota and acceptability of fecal microbiota transplantation in various diseases.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e14320}, doi = {10.1111/nmo.14320}, pmid = {35037353}, issn = {1365-2982}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is now evaluated in various diseases. However, large-scale population treatment may encounter feasibility issues in terms of acceptance. We aim to evaluate patient knowledge of gut microbiota and the acceptability of FMT in various diseases.
METHODS: Patients of Carenity's French online community were invited by email to participate in a questionnaire. The following parameters were assessed: patient's principal illness and duration, demographic data, therapeutics, dietary habits, knowledge of gut microbiota, probiotics and FMT, and its acceptability.
KEY RESULTS: In total, 877 patients participated in the online questionnaire: 156 with inflammatory bowel disease (17.8%), 127 with rheumatoid arthritis (14.5%), 222 with ankylosing spondylitis (25.3%), 52 with lupus (5.9%), 64 with psoriasis (7.3%), 61 with obesity (7%), and 195 with type 2 diabetes (22.2%). Characteristics of participating patients were similar to those of the entire cohort (n = 23084). Overall, 47.1% (n = 413/877) of patients knew what the microbiota is with no difference among diseases. Knowledge was reported to be developed by patients themselves (203/413; 49.2%) without involving a healthcare professional. If proposed by a healthcare professional, 37.2% (326/877) reported being interested or very interested in undergoing FMT. Factors associated with good acceptability of FMT were the male sex (OR: 1.63, CI95% [1.14 to 2.32]), previous knowledge of FMT (OR: 4.16, CI95% [2.92 to 5.96]), and previous knowledge of gut microbiota (OR: 1.54, CI95% [1.05 to 2.24]).
CONCLUSION AND INFERENCES: Knowledge of gut microbiota is still limited in patients' communities and mainly developed by patients themselves, impacting FMT acceptability.}, }
@article {pmid34508776, year = {2021}, author = {van de Guchte, M and Mondot, S and Doré, J}, title = {Dynamic Properties of the Intestinal Ecosystem Call for Combination Therapies, Targeting Inflammation and Microbiota, in Ulcerative Colitis.}, journal = {Gastroenterology}, volume = {161}, number = {6}, pages = {1969-1981.e12}, doi = {10.1053/j.gastro.2021.08.057}, pmid = {34508776}, issn = {1528-0012}, mesh = {Anti-Inflammatory Agents/adverse effects/*therapeutic use ; Bacteria/*drug effects/genetics/immunology ; Case-Control Studies ; *Cellular Microenvironment ; Colitis, Ulcerative/immunology/microbiology/*therapy ; Combined Modality Therapy ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/*drug effects ; Inflammation Mediators/*antagonists & inhibitors/metabolism ; Intestines/*drug effects/metabolism/microbiology ; Models, Biological ; Remission Induction ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND & AIMS: Intestinal microbiota-host interactions play a major role in health and disease. This has been documented at the microbiota level ("dysbiosis" in chronic immune-mediated diseases) and through the study of specific bacteria-host interactions but rarely at the level of intestinal ecosystem dynamics. However, understanding the behavior of this ecosystem may be key to the successful treatment of disease. We recently postulated that health and disease represent alternative stable states of the intestinal ecosystem (different configurations that can exist under identical external conditions), which would require adapted strategies in disease treatment. Here, we examine if alternative stable states indeed exist in this ecosystem and if they could affect remission from ulcerative colitis (UC).
METHODS: We analyzed data from a study on pediatric UC. The data reflect current treatment practice following the recruitment of treatment-naive patients with new-onset disease. Patients received personalized anti-inflammatory treatments over a period of 1 year. Stool samples at 0, 4, 12, and 52 weeks allowed an estimation of microbiota status (through 16S ribosomal RNA gene sequencing) and host inflammatory status (through the measurement of fecal calprotectin levels).
RESULTS: We identify 4 microbiota states and 4 host states. Longitudinal data show that the improvement of inflammatory status is accompanied by an improvement of microbiota status. However, they also provide strong indications that both improvements are retarded or blocked by alternative states barriers.
CONCLUSIONS: Our observations strongly suggest that inflammation suppression should be combined with microbiota management where possible to improve the efficacy of UC treatment.}, }
@article {pmid35031549, year = {2022}, author = {Messaoudene, M and Pidgeon, R and Richard, C and Ponce, M and Diop, K and Benlaifaoui, M and Nolin-Lapalme, A and Cauchois, F and Malo, J and Belkaid, W and Isnard, S and Fradet, Y and Dridi, L and Velin, D and Oster, P and Raoult, D and Ghiringhelli, F and Boidot, R and Chevrier, S and Kysela, DT and Brun, YV and Falcone, EL and Pilon, G and Plaza Onate, F and Gitton-Quent, O and Le Chatelier, E and Durand, S and Kroemer, G and Elkrief, A and Marette, A and Castagner, B and Routy, B}, title = {A natural polyphenol exerts antitumor activity and circumvents anti-PD-1 resistance through effects on the gut microbiota.}, journal = {Cancer discovery}, volume = {}, number = {}, pages = {}, doi = {10.1158/2159-8290.CD-21-0808}, pmid = {35031549}, issn = {2159-8290}, abstract = {Several approaches to manipulate the gut microbiome for improving the activity of cancer immune checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC, Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti-PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC. Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/Foxp3+CD4+ ratio within the tumor microenvironment. Moreover, castalagin induced metabolic changes, resulting in an increase in taurine conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti-PD-1 activity. Finally, we found that castalagin binds to Ruminococcus bromii and promoted an anticancer response. Altogether, our results identify castalagin as a polyphenol that acts as a prebiotic to circumvent anti-PD-1 resistance.}, }
@article {pmid35028606, year = {2021}, author = {Blake, SJ and James, J and Ryan, FJ and Caparros-Martin, J and Eden, GL and Tee, YC and Salamon, JR and Benson, SC and Tumes, DJ and Sribnaia, A and Stevens, NE and Finnie, JW and Kobayashi, H and White, DL and Wesselingh, SL and O'Gara, F and Lynn, MA and Lynn, DJ}, title = {The immunotoxicity, but not anti-tumor efficacy, of anti-CD40 and anti-CD137 immunotherapies is dependent on the gut microbiota.}, journal = {Cell reports. Medicine}, volume = {2}, number = {12}, pages = {100464}, doi = {10.1016/j.xcrm.2021.100464}, pmid = {35028606}, issn = {2666-3791}, abstract = {Immune agonist antibodies (IAAs) are promising immunotherapies that target co-stimulatory receptors to induce potent anti-tumor immune responses, particularly when combined with checkpoint inhibitors. Unfortunately, their clinical translation is hampered by serious dose-limiting, immune-mediated toxicities, including high-grade and sometimes fatal liver damage, cytokine release syndrome (CRS), and colitis. We show that the immunotoxicity, induced by the IAAs anti-CD40 and anti-CD137, is dependent on the gut microbiota. Germ-free or antibiotic-treated mice have significantly reduced colitis, CRS, and liver damage following IAA treatment compared with conventional mice or germ-free mice recolonized via fecal microbiota transplant. MyD88 signaling is required for IAA-induced CRS and for anti-CD137-induced, but not anti-CD40-induced, liver damage. Importantly, antibiotic treatment does not impair IAA anti-tumor efficacy, alone or in combination with anti-PD1. Our results suggest that microbiota-targeted therapies could overcome the toxicity induced by IAAs without impairing their anti-tumor activity.}, }
@article {pmid34941392, year = {2021}, author = {Spencer, CN and McQuade, JL and Gopalakrishnan, V and McCulloch, JA and Vetizou, M and Cogdill, AP and Khan, MAW and Zhang, X and White, MG and Peterson, CB and Wong, MC and Morad, G and Rodgers, T and Badger, JH and Helmink, BA and Andrews, MC and Rodrigues, RR and Morgun, A and Kim, YS and Roszik, J and Hoffman, KL and Zheng, J and Zhou, Y and Medik, YB and Kahn, LM and Johnson, S and Hudgens, CW and Wani, K and Gaudreau, PO and Harris, AL and Jamal, MA and Baruch, EN and Perez-Guijarro, E and Day, CP and Merlino, G and Pazdrak, B and Lochmann, BS and Szczepaniak-Sloane, RA and Arora, R and Anderson, J and Zobniw, CM and Posada, E and Sirmans, E and Simon, J and Haydu, LE and Burton, EM and Wang, L and Dang, M and Clise-Dwyer, K and Schneider, S and Chapman, T and Anang, NAS and Duncan, S and Toker, J and Malke, JC and Glitza, IC and Amaria, RN and Tawbi, HA and Diab, A and Wong, MK and Patel, SP and Woodman, SE and Davies, MA and Ross, MI and Gershenwald, JE and Lee, JE and Hwu, P and Jensen, V and Samuels, Y and Straussman, R and Ajami, NJ and Nelson, KC and Nezi, L and Petrosino, JF and Futreal, PA and Lazar, AJ and Hu, J and Jenq, RR and Tetzlaff, MT and Yan, Y and Garrett, WS and Huttenhower, C and Sharma, P and Watowich, SS and Allison, JP and Cohen, L and Trinchieri, G and Daniel, CR and Wargo, JA}, title = {Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response.}, journal = {Science (New York, N.Y.)}, volume = {374}, number = {6575}, pages = {1632-1640}, doi = {10.1126/science.aaz7015}, pmid = {34941392}, issn = {1095-9203}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; F32 CA260769/CA/NCI NIH HHS/United States ; R01 AI143886/AI/NIAID NIH HHS/United States ; P30 CA013696/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; R01 AI109294/AI/NIAID NIH HHS/United States ; R01 AI133822/AI/NIAID NIH HHS/United States ; P50 CA221703/CA/NCI NIH HHS/United States ; U54 CA224070/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cohort Studies ; *Dietary Fiber ; Fatty Acids, Volatile/analysis ; Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Immunotherapy ; Male ; Melanoma/immunology/microbiology/*therapy ; Melanoma, Experimental/immunology/microbiology/therapy ; Mice ; Mice, Inbred C57BL ; *Probiotics ; Progression-Free Survival ; T-Lymphocytes ; }, abstract = {[Figure: see text].}, }
@article {pmid35024588, year = {2022}, author = {Wang, Y and Tang, J and Lv, Q and Tan, Y and Dong, X and Liu, H and Zhao, N and He, Z and Kou, Y and Tan, Y and Liu, XA and Wang, L and Liu, YY and Dai, L}, title = {Establishment and resilience of transplanted gut microbiota in aged mice.}, journal = {iScience}, volume = {25}, number = {1}, pages = {103654}, doi = {10.1016/j.isci.2021.103654}, pmid = {35024588}, issn = {2589-0042}, abstract = {The maintenance of healthy and resilient gut microbiota is critical for the life quality and healthspan of the elderly. Fecal microbiota transplantation (FMT) has been increasingly used to restore healthy gut microbiota. We systemically studied the establishment and resilience of transplanted microbiota after autologous versus heterologous FMT in aged recipients. Gut microbiota of aged mice (20 months old) failed to restore their original diversity and composition over 8 weeks via spontaneous recovery after antibiotics treatment; in contrast, FMT using either autologous or heterologous (2 months old from a different vendor) donors facilitated the recovery successfully, established donor-like microbiota states, and affected host gene expression profile. Furthermore, the transplanted microbiota established by heterologous FMT is not resilient during chemical-induced colonic inflammation, in contrast to that of autologous FMT. Our findings highlighted the need to monitor the long-term stability of transplanted gut microbiota and to perform multiple FMT when necessary.}, }
@article {pmid35023946, year = {2022}, author = {Azimirad, M and Jo, Y and Kim, MS and Jeong, M and Shahrokh, S and Asadzadeh Aghdaei, H and Zali, MR and Lee, S and Yadegar, A and Shin, JH}, title = {Alterations and Prediction of Functional Profiles of Gut Microbiota After Fecal Microbiota Transplantation for Iranian Recurrent Clostridioides difficile Infection with Underlying Inflammatory Bowel Disease: A Pilot Study.}, journal = {Journal of inflammation research}, volume = {15}, number = {}, pages = {105-116}, doi = {10.2147/JIR.S338212}, pmid = {35023946}, issn = {1178-7031}, abstract = {Background and Purpose: Fecal microbiota transplantation (FMT) has emerged for the therapeutic treatment of recurrent Clostridioides difficile infection (rCDI) with concurrent inflammatory bowel disease (IBD). As the first Iranian population cohort, we examined how gut microbiota and their functional profiles change in Iranian rCDI patients with underlying IBD before and after FMT.
Patients and Methods: FMT was performed to eight IBD patients via colonoscopy. Profiles of gut microbiota from donors and recipients were investigated using 16S rRNA gene sequence analysis.
Results: Patients experienced no IBD flare-ups or other adverse effects, and all recovered to full health. Moreover, all rCDI patients lacked the Bacteroidetes present in donor samples. After FMT, the proportion of Bacteroidetes increased until a normal range was achieved. More specifically, the relative abundance of Prevotella was found to increase significantly following FMT. Prevotella was also found to correlate negatively with inflammation metrics, suggesting that Prevotella may be a key factor for resolving CDI and IBD. Gut microbiota diversity was found to increase following FMT, while dysbiosis decreased. However, the similarity of microbial communities of host and recipients did not increase, and wide variation in the extent of donor stool engraftment indicated that the gut bacterial communities of recipients do not shift towards those of donors.
Conclusion: FMT leads to significant alterations of the community structure of gut bacteria in rCDI patients with IBD. The change in relative abundance of Proteobacteria and bacterial diversity indicated that FMT promotes recovery from intestinal permeability and inflammation in rCDI patients. Moreover, strong negative correlation between Prevotella and inflammation index, and decreased dysbiosis index advocate that the improvement of CDI is possibly due to gut microbiome alteration. Collectively, our findings show that FMT would be a promising therapy to help reprogram the gut microbiome of Iranian rCDI patients with IBD.}, }
@article {pmid33443023, year = {2021}, author = {Zhang, C and Xiong, B and Chen, L and Ge, W and Yin, S and Feng, Y and Sun, Z and Sun, Q and Zhao, Y and Shen, W and Zhang, H}, title = {Rescue of male fertility following faecal microbiota transplantation from alginate oligosaccharide-dosed mice.}, journal = {Gut}, volume = {70}, number = {11}, pages = {2213-2215}, pmid = {33443023}, issn = {1468-3288}, mesh = {Alginates ; Animals ; *Fecal Microbiota Transplantation ; Fertility ; *Gastrointestinal Microbiome ; Male ; Mice ; Oligosaccharides ; }, }
@article {pmid35017486, year = {2022}, author = {Hu, H and Shao, W and Liu, Q and Liu, N and Wang, Q and Xu, J and Zhang, X and Weng, Z and Lu, Q and Jiao, L and Chen, C and Sun, H and Jiang, Z and Zhang, X and Gu, A}, title = {Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {252}, pmid = {35017486}, issn = {2041-1723}, support = {81770626//National Natural Science Foundation of China (National Science Foundation of China)/ ; 91839102//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81770625//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81573174//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82070654//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Cholesterol gallstone disease is a worldwide common disease. Cholesterol supersaturation in gallbladder bile is the prerequisite for its pathogenesis, while the mechanism is not completely understood. In this study, we find enrichment of gut microbiota (especially Desulfovibrionales) in patients with gallstone disease. Fecal transplantation of gut microbiota from gallstone patients to gallstone-resistant strain of mice can induce gallstone formation. Carrying Desulfovibrionales is associated with enhanced cecal secondary bile acids production and increase of bile acid hydrophobicity facilitating intestinal cholesterol absorption. Meanwhile, the metabolic product of Desulfovibrionales, H2S increase and is shown to induce hepatic FXR and inhibit CYP7A1 expression. Mice carrying Desulfovibrionales present induction of hepatic expression of cholesterol transporters Abcg5/g8 to promote biliary secretion of cholesterol as well. Our study demonstrates the role of gut microbiota, Desulfovibrionales, as an environmental regulator contributing to gallstone formation through its influence on bile acid and cholesterol metabolism.}, }
@article {pmid34245901, year = {2021}, author = {Reigadas, E and van Prehn, J and Falcone, M and Fitzpatrick, F and Vehreschild, MJGT and Kuijper, EJ and Bouza, E and , }, title = {How to: prophylactic interventions for prevention of Clostridioides difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {27}, number = {12}, pages = {1777-1783}, doi = {10.1016/j.cmi.2021.06.037}, pmid = {34245901}, issn = {1469-0691}, mesh = {*Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; *Clostridium Infections/prevention & control/therapy ; *Fecal Microbiota Transplantation ; Humans ; Recurrence ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhoea, despite existing guidelines for infection control measures and antimicrobial stewardship. The high associated health and economic burden of CDI calls for novel strategies to prevent the development and spread of CDI in susceptible patients.
OBJECTIVES: We aim to review CDI prophylactic treatment strategies and their implementation in clinical practice.
SOURCES: We searched PubMed, Embase, Emcare, Web of Science, and the COCHRANE Library databases to identify prophylactic interventions aimed at prevention of CDI. The search was restricted to articles published in English since 2012.
CONTENT: A toxin-based vaccine candidate is currently being investigated in a phase III clinical trial. However, a recent attempt to develop a toxin-based vaccine has failed. Conventional probiotics have not yet proved to be an effective strategy for prevention of CDI. New promising microbiota-based interventions that bind and inactivate concomitantly administered antibiotics, such as ribaxamase and DAV-132, have been developed. Prophylaxis of CDI with C. difficile antibiotics should not be performed routinely and should be considered only for secondary prophylaxis in very selected patients who are at the highest imminent risk for recurrent CDI (R-CDI) after a thorough evaluation. Faecal microbiota transplantation (FMT) has proved to be a very effective treatment for patients with multiple recurrences. Bezlotoxumab provides protection against R-CDI, mainly in patients with primary episodes and a high risk of relapse.
IMPLICATIONS: There are no proven effective, evidenced-based prophylaxis options for primary CDI. As for secondary prevention, FMT is considered the option of choice in patients with multiple recurrences. Bezlotoxumab can be added to standard treatment for patients at high risk for R-CDI. The most promising strategies are those aimed at reducing changes in intestinal microbiota and development of a new effective non-toxin-based vaccine.}, }
@article {pmid33514598, year = {2021}, author = {Arnoriaga-Rodríguez, M and Mayneris-Perxachs, J and Contreras-Rodríguez, O and Burokas, A and Ortega-Sanchez, JA and Blasco, G and Coll, C and Biarnés, C and Castells-Nobau, A and Puig, J and Garre-Olmo, J and Ramos, R and Pedraza, S and Brugada, R and Vilanova, JC and Serena, J and Barretina, J and Gich, J and Pérez-Brocal, V and Moya, A and Fernández-Real, X and Ramio-Torrentà, L and Pamplona, R and Sol, J and Jové, M and Ricart, W and Portero-Otin, M and Maldonado, R and Fernández-Real, JM}, title = {Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways.}, journal = {Gut}, volume = {70}, number = {12}, pages = {2283-2296}, pmid = {33514598}, issn = {1468-3288}, mesh = {Adult ; Aged ; Amino Acids, Aromatic/*metabolism ; Animals ; Carbon/*metabolism ; Cross-Sectional Studies ; Fatty Liver/microbiology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; *Inhibition, Psychological ; Male ; Mice ; Middle Aged ; Obesity/*complications ; Phenotype ; Transcriptome ; }, abstract = {BACKGROUND: Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits.
METHODS: We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics.
RESULTS: An interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism (thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor's bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient's mice.
CONCLUSION: These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.}, }
@article {pmid35014601, year = {2022}, author = {Singh, P and Alm, EJ and Kelley, JM and Cheng, V and Smith, M and Kassam, Z and Nee, J and Iturrino, J and Lembo, A}, title = {Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2020067}, doi = {10.1080/19490976.2021.2020067}, pmid = {35014601}, issn = {1949-0984}, abstract = {Fecal microbiota transplantation (FMT) is an attractive strategy to correct microbial dysbiosis in diarrhea-predominant irritable bowel syndrome (IBS-D). Although the mechanism of FMT is thought to be bacterial engraftment, the best approach to achieve engraftment after FMT in IBS-D (and other diseases) is not clear. We evaluated the effect of FMT (with or without pretreatment with antibiotics) on gut microbiome and symptoms in patients with IBS-D. In this randomized, placebo-controlled, single-center study, 44 patients with IBS-D with a least moderate severity (IBS severity scoring system, i.e., IBS-SSS, ≥175) were randomly assigned to one of four groups: single-dose oral FMT alone, single-dose oral FMT following a 7-day pretreatment course of Ciprofloxacin and Metronidazole (CM-FMT) or Rifaximin (R-FMT), or Placebo FMT. Primary endpoint was engraftment post-FMT and secondary endpoints were changes in IBS-SSS, and IBS-quality of life (IBS-QOL) at week 10. Median engraftment was significantly different among the three FMT groups (P = .013). Engraftment post-FMT was significantly higher in the FMT alone arm (15.5%) compared to that in R-FMT group (5%, P = .04) and CM-FMT group (2.4%, P = .002). The mean change in IBS-SSS and IBS-QOL from baseline were not significantly different among the four groups or between the three FMT groups combined vs. placebo at week 10. In summary, antibiotic pretreatment significantly reduced bacterial engraftment after FMT in patients with IBS-D.}, }
@article {pmid35011199, year = {2021}, author = {Chen, S and Luo, S and Yan, C}, title = {Gut Microbiota Implications for Health and Welfare in Farm Animals: A Review.}, journal = {Animals : an open access journal from MDPI}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/ani12010093}, pmid = {35011199}, issn = {2076-2615}, support = {2019A1515110598//the Joint Fund of Basic and Applied Basic Research Fund of Guangdong Province/ ; 2019B030301010//the Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding/ ; }, abstract = {In the past few decades, farm animal health and welfare have been paid increasing concern worldwide. Farm animal health and welfare are generally assessed by the measurements of physical health, immune response, behavior, and physiological indicators. The gut microbiota has been reported to have a great influence on host phenotypes, possibly via the immune processes, neural functions, and endocrine pathways, thereby influencing host phenotypes. However, there are few reviews regarding farm animals' health and welfare status concerning the gut microbiota. In this point of view, (1) we reviewed recent studies showing that gut microbiota (higher alpha diversity, beneficial composition, and positive functions) effectively influenced health characteristics, immunity, behaviors, and stress response in farm animals (such as pigs, chickens, and cows), which would provide a novel approach to measure and evaluate the health status and welfare of farm animals. In addition, fecal microbiota transplantation (FMT) as one of the methods can modulate the recipient individual's gut microbiota to realize the expected phenotype. Further, (2) we highlighted the application of FMT on the improvement of the production performance, the reduction in disease and abnormal behavior, as well as the attenuation of stress in farm animals. It is concluded that the gut microbiota can be scientifically used to assess and improve the welfare of farm animals. Moreover, FMT may be a helpful strategy to reduce abnormal behavior and improve stress adaption, as well as the treatment of disease for farm animals. This review suggests that gut microbiota is a promising field to evaluate and improve animal welfare.}, }
@article {pmid35011044, year = {2021}, author = {Iatcu, CO and Steen, A and Covasa, M}, title = {Gut Microbiota and Complications of Type-2 Diabetes.}, journal = {Nutrients}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/nu14010166}, pmid = {35011044}, issn = {2072-6643}, support = {120/16.09.2016.//European Regional Development Fund through Competitiveness Operational Program/ ; }, abstract = {The gut microbiota has been linked to the emergence of obesity, metabolic syndrome and the onset of type 2 diabetes through decreased glucose tolerance and insulin resistance. Uncontrolled diabetes can lead to serious health consequences such as impaired kidney function, blindness, stroke, myocardial infarction and lower limb amputation. Despite a variety of treatments currently available, cases of diabetes and resulting complications are on the rise. One promising new approach to diabetes focuses on modulating the gut microbiota with probiotics, prebiotics, synbiotics and fecal microbial transplantation. Differences in gut microbiota composition have been observed in preclinical animal models as well as patients with type 2 diabetes and complications such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, cerebrovascular disease, coronary heart disease and peripheral artery disease compared to healthy controls. Severity of gut microbiota dysbiosis was associated with disease severity and restoration with probiotic administration in animal models and human patients has been associated with improvement of symptoms and disease progression. Characterizing the gut microbiota dysbiosis in different diseases and determining a causal relationship between the gut microbiota and disease can be beneficial in formulating therapeutic interventions for type 2 diabetes and associated complications. In this review, we present the most important findings regarding the role of the gut microbiota in type 2 diabetes and chronic complications as well as their underlying mechanisms.}, }
@article {pmid35010223, year = {2021}, author = {Liu, P and Zhou, W and Xu, W and Peng, Y and Yan, Y and Lu, L and Mi, J and Zeng, X and Cao, Y}, title = {The Main Anthocyanin Monomer from Lycium ruthenicum Murray Fruit Mediates Obesity via Modulating the Gut Microbiota and Improving the Intestinal Barrier.}, journal = {Foods (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, doi = {10.3390/foods11010098}, pmid = {35010223}, issn = {2304-8158}, support = {2019BFG02026//Research and Development Project funded by Ningxia Hui Autonomous Region of China/ ; PAPD//Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, abstract = {Anthocyanins have been shown to exert certain antiobesity properties, but the specific relationship between anthocyanin-induced beneficial effects and the gut microbiota remains unclear. Petunidin-3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(β-D-glucopyranoside) (P3G) is the main anthocyanin monomer from the fruit of Lycium ruthenicum Murray. Therefore, in this study, we investigated the antiobesity and remodeling effects of P3G on gut microbiota through a high-fat diet (HFD)-induced obesity mouse model and a fecal microbiota transplantation experiment. P3G was found to reduce body weight gain, fat accumulation, and liver steatosis in HFD-induced obese mice. Moreover, supplementation with P3G alleviated the HFD-induced imbalance in gut microbiota composition, and transferring the P3G-regulated gut microbiota to recipient mice provided comparable protection against obesity. This is the first time evidence is provided that P3G has an antiobesity effect by changing the intestinal microbiota. Our present data highlight a link between P3G intervention and enhancement in gut barrier integrity. This may be a promising option for obesity prevention.}, }
@article {pmid35008915, year = {2022}, author = {Sevcikova, A and Izoldova, N and Stevurkova, V and Kasperova, B and Chovanec, M and Ciernikova, S and Mego, M}, title = {The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, doi = {10.3390/ijms23010488}, pmid = {35008915}, issn = {1422-0067}, support = {APVV-19-0411, APVV-20-0158//Slovak Research and Development Agency/ ; 1/0327/19, 2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, abstract = {Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.}, }
@article {pmid34718953, year = {2022}, author = {Bhattacharjee, A and Dubey, S and Sharma, S}, title = {Storage of soil microbiome for application in sustainable agriculture: prospects and challenges.}, journal = {Environmental science and pollution research international}, volume = {29}, number = {3}, pages = {3171-3183}, pmid = {34718953}, issn = {1614-7499}, support = {BT/PR27680/BCE/8/1434/2018//Department of Biotechnology , Ministry of Science and Technology/ ; PDF/2018/001905//Science and Engineering Research Board/ ; fellowship//Indian Institute of Technology Delhi/ ; }, mesh = {Agriculture ; *Microbiota ; *Soil ; Soil Microbiology ; }, abstract = {Soil microbiome is a dynamic micro-ecosystem driving and fine-tuning several biological processes in the global macro-ecosystems. Its tremendous potential towards mediating sustainability in the ecosystem necessitates the urgent need to store it optimally and efficiently as "next-generation biologicals" for future applications via soil transplantation. The challenge, therefore, is to devise a strategy for the storage of soil microbiome such that its "functionality" is preserved for later application. This review discusses the current endeavours made towards storage of the soil microbiome. The methods for assessing the integrity of soil microbiome by targeting the structural diversity and functional potential of the preserved microbiomes have also been discussed. Further, the success stories related to the storage of fecal microbiome for application in transplants have also been highlighted. This is done primarily with the objective of learning lessons, and parallel application of the knowledge gained, in bringing about improvement in the research domain of soil microbiome storage. Subsequently, the limitations of current techniques of preservation have also been delineated. Further, the open questions in the area have been critically discussed. In conclusion, possible alternatives for storage, comprehensive analyses of the composition of the stored microbiome and their potential have been presented.}, }
@article {pmid35004750, year = {2021}, author = {Wang, H and Wang, H and Sun, Y and Ren, Z and Zhu, W and Li, A and Cui, G}, title = {Potential Associations Between Microbiome and COVID-19.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {785496}, doi = {10.3389/fmed.2021.785496}, pmid = {35004750}, issn = {2296-858X}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis. The disease is characterized by strong infectivity, high morbidity, and high mortality. It is still spreading in some countries. Microbiota and their metabolites affect human physiological health and diseases by participating in host digestion and nutrition, promoting metabolic function, and regulating the immune system. Studies have shown that human microecology is associated with many diseases, including COVID-19. In this research, we first reviewed the microbial characteristics of COVID-19 from the aspects of gut microbiome, lung microbime, and oral microbiome. We found that significant changes take place in both the gut microbiome and airway microbiome in patients with COVID-19 and are characterized by an increase in conditional pathogenic bacteria and a decrease in beneficial bacteria. Then, we summarized the possible microecological mechanisms involved in the progression of COVID-19. Intestinal microecological disorders in individuals may be involved in the occurrence and development of COVID-19 in the host through interaction with ACE2, mitochondria, and the lung-gut axis. In addition, fecal bacteria transplantation (FMT), prebiotics, and probiotics may play a positive role in the treatment of COVID-19 and reduce the fatal consequences of the disease.}, }
@article {pmid35003127, year = {2021}, author = {Yuan, B and Lu, XJ and Wu, Q}, title = {Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {800796}, doi = {10.3389/fimmu.2021.800796}, pmid = {35003127}, issn = {1664-3224}, abstract = {Acute central nervous system (CNS) injuries, including stroke, traumatic brain injury (TBI), and spinal cord injury (SCI), are the common causes of death or lifelong disabilities. Research into the role of the gut microbiota in modulating CNS function has been rapidly increasing in the past few decades, particularly in animal models. Growing preclinical and clinical evidence suggests that gut microbiota is involved in the modulation of multiple cellular and molecular mechanisms fundamental to the progression of acute CNS injury-induced pathophysiological processes. The altered composition of gut microbiota after acute CNS injury damages the equilibrium of the bidirectional gut-brain axis, aggravating secondary brain injury, cognitive impairments, and motor dysfunctions, which leads to poor prognosis by triggering pro-inflammatory responses in both peripheral circulation and CNS. This review summarizes the studies concerning gut microbiota and acute CNS injuries. Experimental models identify a bidirectional communication between the gut and CNS in post-injury gut dysbiosis, intestinal lymphatic tissue-mediated neuroinflammation, and bacterial-metabolite-associated neurotransmission. Additionally, fecal microbiota transplantation, probiotics, and prebiotics manipulating the gut microbiota can be used as effective therapeutic agents to alleviate secondary brain injury and facilitate functional outcomes. The role of gut microbiota in acute CNS injury would be an exciting frontier in clinical and experimental medicine.}, }
@article {pmid35000023, year = {2022}, author = {Suchman, K and Luo, Y and Grinspan, A}, title = {Fecal Microbiota Transplant for Clostridioides Difficile Infection Is Safe and Efficacious in an Immunocompromised Cohort.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {35000023}, issn = {1573-2568}, abstract = {BACKGROUND: Immunocompromised patients are particularly vulnerable to Clostridioides difficile infection (CDI), hospitalizations and recurrences. Studies have shown that fecal microbiota transplant (FMT) is safe and effective in immunocompromised patients.
AIMS: To examine the outcomes of FMT for CDI in a diverse cohort of immunocompromised patients stratified by medication class.
METHODS: We performed a retrospective, long-term follow-up study of FMT in immunocompromised patients, including those undergoing chemotherapy, with inflammatory bowel disease (IBD) on immunomodulators, prior solid organ transplant on immunosuppressants, on chronic steroids 20 mg/day or higher for a minimum of three months, or HIV positive. Primary outcomes included adjusted primary cure rate within 8 weeks, as well as rates of non-response, recurrences, relapses and adverse events. Secondary outcomes included adjusted overall cure rate. Primary cure rate was defined as patients not requiring repeat CDI treatment within 8 weeks after index FMT, and overall cure rate was defined as resolution of CDI symptoms after index FMT or second FMT.
RESULTS: Our cohort included 77 immunosuppressed patients (53.2% female, median age 39.1 years, range 7-95 years). The majority of our cohort were IBD patients on biologics (62.3%). Adjusting for colectomies and deaths, our primary and overall cure rates were 85.1% and 86.5%, respectively. Twelve patients received FMT for severe or fulminant CDI with a 3-month survival rate of 91.7%. 11.7% of patients experienced serious adverse events following FMT.
CONCLUSIONS: Our study supports the efficacy and safety of FMT in immunocompromised patients, though future research is needed to further ascertain the potential effects of immunosuppression on FMT outcomes.}, }
@article {pmid34873153, year = {2021}, author = {Gao, A and Su, J and Liu, R and Zhao, S and Li, W and Xu, X and Li, D and Shi, J and Gu, B and Zhang, J and Li, Q and Wang, X and Zhang, Y and Xu, Y and Lu, J and Ning, G and Hong, J and Bi, Y and Gu, W and Wang, J and Wang, W}, title = {Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {7080}, pmid = {34873153}, issn = {2041-1723}, mesh = {3T3-L1 Cells ; Androgens/*pharmacology ; Animals ; Anti-Bacterial Agents/pharmacology ; Cell Line ; Dihydrotestosterone/pharmacology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/genetics/physiology ; Glucose/*metabolism ; Glutamic Acid/blood ; Glutamine/blood ; Hep G2 Cells ; Homeostasis/*drug effects ; Humans ; Insulin Resistance/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Orchiectomy ; Sex Factors ; }, abstract = {Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes.}, }
@article {pmid34864063, year = {2022}, author = {Pradhan, S and Ray, P and Aich, P}, title = {Microbiota transplantation from younger to older mice could restore lost immunity to effectively clear salmonella infection in Th2-biased BALB/c mice.}, journal = {Life sciences}, volume = {288}, number = {}, pages = {120201}, doi = {10.1016/j.lfs.2021.120201}, pmid = {34864063}, issn = {1879-0631}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/*growth & development ; Cecum/*transplantation ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Homeostasis ; Immunity, Innate ; Male ; Metabolome ; Metagenomics ; Mice ; Mice, Inbred BALB C ; Salmonella/drug effects/genetics/*immunology/metabolism ; Salmonella Infections/immunology/metabolism/microbiology/*therapy ; Th2 Cells/*immunology ; }, abstract = {AIMS: The composition, overtly abundance, and diversity of gut microbiota, play a significant role in maintaining physiological homeostasis with age. Reports revealed that the gut microbial profile might be correlated with immunity and metabolism. It is, therefore, tantamount to know if an older individual can achieve the immunity and metabolic profile of a younger individual by receiving the gut microbiome of a younger individual. In the current report, we have studied the effects of cecal microbiota transplantation (CMT) from younger to older mice.
MATERIALS AND METHODS: In this study, older BALB/c mice (23 weeks) received CMT from younger BALB/c mice (3 weeks).
KEY FINDINGS: CMT recipient mice showed altered expressions of immune and tight junction protein genes in the colon of mice, while the non-CMT recipient mice did not. Older mice were treated with AVNM to make them compatible with CMT. Further data from metabolite studies revealed that AVNM treatment mainly affected the aromatic amino acid biosynthesis pathway while CMT mostly affected the metabolism of different carbohydrates. We repeated the analysis in C57BL/6 mice without any significant effects of CMT.
SIGNIFICANCE: Results revealed that mice who received CMT showed more efficient restoration of gut microbiota than non-CMT recipient mice. CMT caused the alleviation of Salmonella infection and efficient recovery of the cecal index in the mice following antibiotics treatment.}, }
@article {pmid34838850, year = {2022}, author = {Chen, L and Li, R and Wang, Z and Zhang, Z and Wang, J and Qiao, Y and Huang, Y and Liu, W}, title = {Lactate-utilizing bacteria ameliorates DSS-induced colitis in mice.}, journal = {Life sciences}, volume = {288}, number = {}, pages = {120179}, doi = {10.1016/j.lfs.2021.120179}, pmid = {34838850}, issn = {1879-0631}, mesh = {Adult ; Animals ; Bacteria/*growth & development ; Colitis/chemically induced/microbiology/pathology/*prevention & control ; Dextran Sulfate/*toxicity ; Dysbiosis/chemically induced/microbiology/pathology/prevention & control ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Humans ; Lactic Acid/*metabolism ; Male ; Mice, Inbred C57BL ; Probiotics/*administration & dosage ; Young Adult ; }, abstract = {Inflammatory bowel diseases (IBD) stem from alterations in the intestinal immune system and microbial dysbiosis, but the precise interactions between bacteria and IBD remain obscure. The commensal microbiota have a profound impact on human health and diseases. Here, we developed a selective culture medium for lactate-utilizing bacteria (LUB) that function as candidate probiotics to ameliorate IBD using a mouse model. Firstly, LUB, including Megasphaera, were enriched from human faeces using a selective medium with lactate. LUB efficiently attenuated the pathology of colitis induced by dextran sulphate sodium (DSS). Next, LUB administration counteracted the dysbiosis associated with the intestinal inflammatory process, and elevated the proportion of Escherichia-Shigella in intestines. Moreover, E. coli isolated from healthy faeces downstream recapitulated lactate-utilizing bacterial community to ameliorate the severity of DSS-induced acute colitis. In conclusion, our finding revealed that LUB were sufficient to exert inflammatory protection against colitis in mice, highlighting a novel therapeutic strategy to use LUB as potentially curable probiotics for therapeutic manipulation for IBD.}, }
@article {pmid33870869, year = {2021}, author = {Wuethrich, I and W Pelzer, B and Khodamoradi, Y and Vehreschild, MJGT}, title = {The role of the human gut microbiota in colonization and infection with multidrug-resistant bacteria.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-13}, pmid = {33870869}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Bacterial Infections/*immunology/*microbiology/*therapy/virology ; Bacteriophages ; Biological Therapy ; *Drug Resistance, Multiple, Bacterial ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Host Microbial Interactions ; Humans ; *Immunity ; Prebiotics ; Probiotics ; Vaccines ; }, abstract = {About 100 years ago, the first antibiotic drug was introduced into health care. Since then, antibiotics have made an outstanding impact on human medicine. However, our society increasingly suffers from collateral damage exerted by these highly effective drugs. The rise of resistant pathogen strains, combined with a reduction of microbiota diversity upon antibiotic treatment, has become a significant obstacle in the fight against invasive infections worldwide.Alternative and complementary strategies to classical "Fleming antibiotics" comprise microbiota-based treatments such as fecal microbiota transfer and administration of probiotics, live-biotherapeutics, prebiotics, and postbiotics. Other promising interventions, whose efficacy may also be influenced by the human microbiota, are phages and vaccines. They will facilitate antimicrobial stewardship, to date the only globally applied antibiotic resistance mitigation strategy.In this review, we present the available evidence on these nontraditional interventions, highlight their interaction with the human microbiota, and discuss their clinical applicability.}, }
@article {pmid33563544, year = {2021}, author = {Liwinski, T and Leshem, A and Elinav, E}, title = {Breakthroughs and Bottlenecks in Microbiome Research.}, journal = {Trends in molecular medicine}, volume = {27}, number = {4}, pages = {298-301}, doi = {10.1016/j.molmed.2021.01.003}, pmid = {33563544}, issn = {1471-499X}, mesh = {Diet ; Fecal Microbiota Transplantation ; Host Microbial Interactions ; Humans ; Metagenomics/methods ; *Microbiota/drug effects/genetics/immunology ; Phage Therapy ; Precision Medicine/trends ; Probiotics ; }, abstract = {Over the past 15 years, the research community has witnessed unprecedented progress in microbiome research. We review this increasing knowledge and first attempts of its clinical application, and also limitations and challenges faced by the research community, in mechanistically understanding host-microbiome interactions and integrating these insights into clinical practice.}, }
@article {pmid33303563, year = {2021}, author = {Haifer, C and Saikal, A and Paramsothy, R and Kaakoush, NO and Leong, RW and Borody, TJ and Kamm, MA and Paramsothy, S}, title = {Response to faecal microbiota transplantation in ulcerative colitis is not sustained long term following induction therapy.}, journal = {Gut}, volume = {70}, number = {11}, pages = {2210-2211}, doi = {10.1136/gutjnl-2020-323581}, pmid = {33303563}, issn = {1468-3288}, mesh = {*Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Induction Chemotherapy ; }, }
@article {pmid34992678, year = {2021}, author = {Sandhu, A and Chopra, T}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile, safety, and pitfalls.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211053105}, doi = {10.1177/17562848211053105}, pmid = {34992678}, issn = {1756-283X}, abstract = {Clostridioides difficile infection (CDI) is one of the leading causes of hospital-acquired infection attributing to substantial morbidity, mortality, and healthcare cost. Recurrent CDI (rCDI) is common and occurs after effective treatment of first episode. Treatment of rCDI is based on accurate diagnoses, due to difficulty in distinguishing between colonization of C. difficile spores or CDI; coronavirus disease 2019 (COVID-19) added to the complexity of diagnoses as both entities can co-occur. It is difficult to eradicate rCDI, and there remains a critical gap regarding treatment of rCDI. The treatment goal of rCDI is to reestablish normal microbiota. Fecal microbiota transplantation (FMT) is suggested as a treatment for second episode of rCDI. Based on the collective evidence of all randomized controlled trials, FMT was reported more efficacious compared with vancomycin or fidaxomicin; however, these trials had limited number of patients and all patients were pre-treated with vancomycin prior to FMT. Furthermore, when comparing various routes of instillation and types of preparation of fecal microbiota, no difference was observed in cure rate. Despite the success rate of FMT, there remains a concern for transmission of infectious agents, such as Gram negative bacteremia or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adverse events (diarrhea and abdominal pain), and reports of new diagnoses (inflammatory bowel disease, weight gain and irritable bowel syndrome). To lessen the risk of transmissible infections, donor screening should be performed, which includes screening for medical comorbidities and infectious pathogens in blood and feces. Scheduling complexities and reimbursement places an additional roadblock for using FMT. Microbiome-based therapies are being developed to eliminate the logistical challenges related to FMT. Large prospective and placebo-controlled studies are needed to evaluate the efficacy and long-term safety of FMT, so its use can be justified in clinical practice.}, }
@article {pmid34992606, year = {2021}, author = {Lai, J and Zhang, P and Jiang, J and Mou, T and Li, Y and Xi, C and Wu, L and Gao, X and Zhang, D and Chen, Y and Huang, H and Li, H and Cai, X and Li, M and Zheng, P and Hu, S}, title = {New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {789647}, doi = {10.3389/fimmu.2021.789647}, pmid = {34992606}, issn = {1664-3224}, abstract = {Tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1) is a robust risk gene of bipolar disorder (BD). However, little is known on the role of TRANK1 in the pathogenesis of BD and whether the gut microbiota is capable of regulating TRANK1 expression. In this study, we first investigated the serum mRNA level of TRANK1 in medication-free patients with a depressive episode of BD, then a mice model was constructed by fecal microbiota transplantation (FMT) to explore the effects of gut microbiota on brain TRANK1 expression and neuroinflammation, which was further verified by in vitro Lipopolysaccharide (LPS) treatment in BV-2 microglial cells and neurons. 22 patients with a depressive episode and 28 healthy individuals were recruited. Serum level of TRANK1 mRNA was higher in depressed patients than that of healthy controls. Mice harboring 'BD microbiota' following FMT presented depression-like phenotype. mRNA levels of inflammatory cytokines and TRANK1 were elevated in mice hippocampus and prefrontal cortex. In vitro, LPS treatment activated the secretion of pro-inflammatory factors in BV-2 cells, which was capable of upregulating the neuronal expression of TRANK1 mRNA. Moreover, primary cortical neurons transfected with plasmid Cytomegalovirus DNA (pcDNA3.1(+)) vector encoding human TRANK1 showed decreased dendritic spine density. Together, these findings add new evidence to the microbiota-gut-brain regulation in BD, indicating that microbiota is possibly involved in the neuropathogenesis of BD by modulating the expression of TRANK1.}, }
@article {pmid34846698, year = {2021}, author = {Wu, LH and Ye, ZN and Peng, P and Xie, WR and Xu, JT and Zhang, XY and Xia, HH and He, XX}, title = {Efficacy and Safety of Washed Microbiota Transplantation to Treat Patients with Mild-to-Severe COVID-19 and Suspected of Having Gut Microbiota Dysbiosis: Study Protocol for a Randomized Controlled Trial.}, journal = {Current medical science}, volume = {41}, number = {6}, pages = {1087-1095}, pmid = {34846698}, issn = {2523-899X}, mesh = {Adult ; Aged ; COVID-19/complications/*microbiology/*therapy ; China ; Clinical Protocols ; Dysbiosis/etiology/*microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; *Gastrointestinal Microbiome ; Humans ; Living Donors ; Male ; Middle Aged ; Prospective Studies ; *SARS-CoV-2 ; Safety ; Single-Blind Method ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Coronavirus disease 2019 (COVID-19) is often accompanied by gastrointestinal symptoms, which are related to gut microbiota dysbiosis (GMD). Whether washed microbiota transplantation (WMT) is an effective treatment for COVID-19 patients suspected of having GMD by restoring the gut microbiota is unknown. This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected of having GMD.
METHODS: This is a randomized, multicenter, single-blind prospective study. COVID-19 patients suspected of having GMD will be randomly divided to receive routine treatment only or to receive routine treatment and WMT. The frequency of WMT will be once a day for three consecutive days. Laboratory and imaging examinations will be performed at admission, 1 and 2 weeks after treatment, and on the day of discharge. Then a telephone follow-up will be conducted at 1st week, 2nd week, and 6th month after discharge. The clinical efficacy and safety of WMT in COVD-19 patients suspected of having GMD and the effects of WMT on the organ function, homeostasis, inflammatory response, intestinal mucosal barrier function, and immunity of the patients will be evaluated.
RESULTS: By following the proposed protocol, WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected of having GMD, and the therapeutic effect is expected to be associated with improvement of the intestinal mucosal barrier function, inflammatory response, and immunity.
CONCLUSION: The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD.}, }
@article {pmid34580480, year = {2021}, author = {Wolter, M and Grant, ET and Boudaud, M and Steimle, A and Pereira, GV and Martens, EC and Desai, MS}, title = {Leveraging diet to engineer the gut microbiome.}, journal = {Nature reviews. Gastroenterology & hepatology}, volume = {18}, number = {12}, pages = {885-902}, pmid = {34580480}, issn = {1759-5053}, mesh = {Autoimmune Diseases/immunology/*microbiology/physiopathology/*therapy ; Combined Modality Therapy ; Diet/*methods ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology/*physiology ; Humans ; Prebiotics ; Primary Prevention/methods ; Probiotics/therapeutic use ; }, abstract = {Autoimmune diseases, including inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, have distinct clinical presentations but share underlying patterns of gut microbiome perturbation and intestinal barrier dysfunction. Their potentially common microbial drivers advocate for treatment strategies aimed at restoring appropriate microbiome function, but individual variation in host factors makes a uniform approach unlikely. In this Perspective, we consolidate knowledge on diet-microbiome interactions in local inflammation, gut microbiota imbalance and host immune dysregulation. By understanding and incorporating the effects of individual dietary components on microbial metabolic output and host physiology, we examine the potential for diet-based therapies for autoimmune disease prevention and treatment. We also discuss tools targeting the gut microbiome, such as faecal microbiota transplantation, probiotics and orthogonal niche engineering, which could be optimized using custom dietary interventions. These approaches highlight paths towards leveraging diet for precise engineering of the gut microbiome at a time of increasing autoimmune disease.}, }
@article {pmid34508775, year = {2022}, author = {Lau, HC and Ng, SC and Yu, J}, title = {Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?.}, journal = {Gastroenterology}, volume = {162}, number = {1}, pages = {9-16}, pmid = {34508775}, issn = {1528-0012}, mesh = {COVID-19/etiology/*microbiology/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Probiotics/therapeutic use ; *SARS-CoV-2 ; Severity of Illness Index ; }, }
@article {pmid34482269, year = {2021}, author = {Farshbafnadi, M and Agah, E and Rezaei, N}, title = {The second brain: The connection between gut microbiota composition and multiple sclerosis.}, journal = {Journal of neuroimmunology}, volume = {360}, number = {}, pages = {577700}, doi = {10.1016/j.jneuroim.2021.577700}, pmid = {34482269}, issn = {1872-8421}, mesh = {Animals ; *Brain-Gut Axis/immunology/physiology ; Disease Models, Animal ; Dysbiosis/*complications/physiopathology/therapy ; Encephalomyelitis, Autoimmune, Experimental/*microbiology/physiopathology ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred Strains ; Mice, Transgenic ; Multiple Sclerosis/etiology/*microbiology/physiopathology/therapy ; Neurodegenerative Diseases/etiology/immunology/microbiology ; Probiotics ; Rats ; Vitamin D/therapeutic use ; }, abstract = {Gut microbiota composition may affect the central nervous system (CNS) and immune function. Several studies have recently examined the possible link between gut microbiota composition and multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Most of these studies agree that patients with MS suffer from dysbiosis. Moreover, an altered proportion of certain phyla of bacteria was detected in the digestive tracts of these patients compared to healthy individuals. This review article gathers information from research papers that have examined the relationship between gut microbiota composition and MS and its possible mechanisms.}, }
@article {pmid33769200, year = {2021}, author = {Glenny, EM and Fouladi, F and Thomas, SA and Bulik-Sullivan, EC and Tang, Q and Djukic, Z and Trillo-Ordonez, YS and A Fodor, A and Tarantino, LM and M Bulik, C and M Carroll, I}, title = {Gut microbial communities from patients with anorexia nervosa do not influence body weight in recipient germ-free mice.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-15}, pmid = {33769200}, issn = {1949-0984}, support = {R01 MH119084/MH/NIMH NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; R01 MH105684/MH/NIMH NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 MH118278/MH/NIMH NIH HHS/United States ; R01 MH120170/MH/NIMH NIH HHS/United States ; T32 DK007686/DK/NIDDK NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; U01 MH109528/MH/NIMH NIH HHS/United States ; }, mesh = {Adiposity ; Adult ; Animals ; Anorexia Nervosa/*microbiology ; Bacteria/*growth & development ; *Body Weight ; Cecum/physiology ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Humans ; Male ; Mice ; Organ Size ; }, abstract = {Anorexia nervosa (AN) is a psychiatric disorder that presents with profound weight dysregulation, metabolic disturbances, and an abnormal composition of gut microbial communities. As the intestinal microbiota can influence host metabolism, the impact of enteric microbial communities from patients with AN on host weight and adiposity was investigated. Germ-free (GF) mice were colonized with fecal microbiotas from either patients with AN (n = 4) prior to inpatient treatment (AN T1, n = 50 recipient mice), the same 4 patients following clinical renourishment (AN T2, n = 53 recipient mice), or age- and sex-matched non-AN controls (n = 4 human donors; non-AN, n = 50 recipient mice). Biological and fecal microbiota data were analyzed with linear mixed-effects models. Body weight did not differ significantly between AN recipient mice (T1 and T2) and non-AN recipient mice following 4 weeks of colonization. Enteric microbiotas from recipient mice colonized with AN T1 and AN T2 fecal microbiotas were more similar to each other compared with enteric microbiotas from non-AN recipient mice. Specific bacterial families in the Actinobacteria, Bacteroidetes, and Firmicutes phyla were significantly associated with body weight, fat mass, and cecum weight irrespective of the donor group. These data suggest that body weight, fat mass, and cecum weight of colonized GF mice are associated with human fecal microbes and independent of donor AN status, although additional analyses with larger cohorts are warranted.}, }
@article {pmid33691599, year = {2021}, author = {Meng, Q and Ma, M and Zhang, W and Bi, Y and Cheng, P and Yu, X and Fu, Y and Chao, Y and Ji, T and Li, J and Chen, Q and Zhang, Q and Li, Y and Shan, J and Bian, H}, title = {The gut microbiota during the progression of atherosclerosis in the perimenopausal period shows specific compositional changes and significant correlations with circulating lipid metabolites.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-27}, pmid = {33691599}, issn = {1949-0984}, mesh = {Animals ; Atherosclerosis/*microbiology/*physiopathology ; Bacteria/growth & development ; Diet, High-Fat ; Disease Progression ; Estradiol/administration & dosage ; Estrogen Replacement Therapy ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; *Lipid Metabolism ; Lipids/blood ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Ovariectomy ; *Perimenopause ; }, abstract = {Atherosclerosis (AS) is exacerbated in the perimenopausal period, which significantly increases the incidence rate of cardiovascular disease. The disruption of the gut microbiota has been associated with AS or menopause, but the specific changes of AS-associated gut microbiota in the perimenopausal period remain largely unknown. As lipid abnormalities are mainly responsible for AS, the relationship between lipid metabolism abnormalities and gut microbiota disruptions during menopause is rarely reported hitherto. In the present study, ApoE-/- mice fed with a high-fat diet (HFD) were subjected to ovariectomy and supplemented with estrogen. The ovariectomized HFD-fed ApoE-/- mice underwent significant AS damage, hepatic lipid damage, hyperlipidemia, and changes of lipid metabolism- and transport-related enzymes. There was significantly higher abundance of some lipid metabolites in the plasma of ovariectomized HFD-fed ApoE-/- mice than in non-ovariectomized ones, including cholesterol esters, triglycerides, phospholipids, and other types of lipids (free fatty acids, acylcarnitine, sphingomyelins, and ceramides). The administration of estrogen significantly reduced the contents of most lipid metabolites. The diversity and composition of gut microbiota evidently changed in ovariectomized HFD-fed ApoE-/- mice, compared to HFD-fed ApoE-/- mice without ovariectomy. In contrast, with estrogen supplementation, the diversity and composition of gut microbiota were restored to approach that of non-ovariectomized HFD-fed ApoE-/- mice, and the relative abundances of some bacteria were even like those of C57BL/6 mice fed with a normal diet. On the other hand, the transplantation of feces from C57BL/6 mice fed with normal diet to ovariectomized HFD-fed ApoE-/- mice was sufficient to correct the hyperlipidemia and AS damage, and to reverse the characteristics changing of lipid metabolomics in ovariectomized HFD-fed ApoE-/- mice. These phenomena were also been observed after transplantation of feces from estrogen-treated ovariectomized HFD-fed ApoE-/- mice to ovariectomized HFD-fed ApoE-/- mice. Moreover, the gut microbiota and lipid metabolites were significantly correlated, demonstrating that the changes of serum lipids may be associated with the gut microbiota disruptions in the perimenopausal period. In conclusion, the gut microbiota during the progression of AS in the perimenopausal period showed specific compositional changes and significant correlations with circulating lipid metabolites. Estrogen supplementation may exert beneficial effects on gut bacteria and lipid metabolism.}, }
@article {pmid34990844, year = {2022}, author = {Aaldijk, E and Vermeiren, Y}, title = {The role of serotonin within the microbiota-gut-brain axis in the development of Alzheimer's disease: a narrative review.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {101556}, doi = {10.1016/j.arr.2021.101556}, pmid = {34990844}, issn = {1872-9649}, abstract = {Alzheimer's disease (AD) is the most common cause of dementia, accounting for more than 50 million patients worldwide. Current evidence suggests the exact mechanism behind this devastating disease to be of multifactorial origin, which seriously complicates the quest for an effective disease-modifying therapy, as well as impedes the search for strategic preventative measures. Of interest, preclinical studies point to serotonergic alterations, either induced via selective serotonin reuptake inhibitors or serotonin receptor (ant)agonists, in mitigating AD brain neuropathology next to its clinical symptoms, the latter being supported by a handful of human intervention trials. Additionally, a substantial amount of preclinical trials highlight the potential of diet, fecal microbiota transplantations, as well as pre- and probiotics in modulating the brain's serotonergic neurotransmitter system, starting from the gut. Whether such interventions could truly prevent, reverse or slow down AD progression likewise, should be initially tested in preclinical studies with AD mouse models, including sufficient analytical measurements both in gut and brain. Thereafter, its potential therapeutic effect could be confirmed in rigorously randomized controlled trials in humans, preferentially across the Alzheimer's continuum, but especially from the prodromal up to the mild stages, where both high adherence to such therapies, as well as sufficient room for noticeable enhancement are feasible still. In the end, such studies might aid in the development of a comprehensive approach to tackle this complex multifactorial disease, since serotonin and its derivatives across the microbiota-gut-brain axis might serve as possible biomarkers of disease progression, next to forming a valuable target in AD drug development. In this narrative review, the available evidence concerning the orchestrating role of serotonin within the microbiota-gut-brain axis in the development of AD is summarized and discussed, and general considerations for future studies are highlighted.}, }
@article {pmid34987741, year = {2021}, author = {Spindelboeck, W and Halwachs, B and Bayer, N and Huber-Krassnitzer, B and Schulz, E and Uhl, B and Gaksch, L and Hatzl, S and Bachmayr, V and Kleissl, L and Kump, P and Deutsch, A and Stary, G and Greinix, H and Gorkiewicz, G and Högenauer, C and Neumeister, P}, title = {Antibiotic use and ileocolonic immune cells in patients receiving fecal microbiota transplantation for refractory intestinal GvHD: a prospective cohort study.}, journal = {Therapeutic advances in hematology}, volume = {12}, number = {}, pages = {20406207211058333}, doi = {10.1177/20406207211058333}, pmid = {34987741}, issn = {2040-6207}, abstract = {Introduction: Treatment-refractory, acute graft-versus-host disease (GvHD) of the lower gastrointestinal tract (GI) after allogeneic hematopoietic stem cell transplantation is life threatening and lacks effective treatment options. While fecal microbiota transplantation (FMT) was shown to ameliorate GI-GvHD, its mechanisms of action and the factors influencing the treatment response in humans remain unclear.The objective of this study is to assess response to FMT treatment, factors influencing response, and to study the mucosal immune cell composition in treatment-refractory GI-GvHD.
Methods: Consecutive patients with treatment-refractory GI-GvHD were treated with up to six endoscopically applied FMTs.
Results: We observed the response to FMT in four out of nine patients with severe, treatment refractory GI-GvHD, associated with a significant survival benefit (p = 0.017). The concomitant use of broad-spectrum antibiotics was the main factor associated with FMT failure (p = 0.048). In addition, antibiotic administration hindered the establishment of donor microbiota after FMT. Unlike in non-responders, the microbiota characteristics (e.g. α- and β-diversity, abundance of anaerobe butyrate-producers) in responders were more significantly similar to those of FMT donors. During active refractory GI-GvHD, an increased infiltrate of T cells, mainly Th17 and CD8+ T cells, was observed in the ileocolonic mucosa of patients, while the number of immunomodulatory cells such as regulatory T-cells and type 3 innate lymphoid cells decreased. After FMT, a change in immune cell patterns was induced, depending on the clinical response.
Conclusion: This study increases the knowledge about the crucial effects of antibiotics in patients given FMT for treatment refractory GI-GvHD and defines the characteristic alterations of ileocolonic mucosal immune cells in this setting.}, }
@article {pmid34986765, year = {2022}, author = {D'Amico, F and Barone, M and Tavella, T and Rampelli, S and Brigidi, P and Turroni, S}, title = {Host microbiomes in tumor precision medicine: how far are we?.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0929867329666220105121754}, pmid = {34986765}, issn = {1875-533X}, abstract = {The human gut microbiome has received a crescendo of attention in recent years, due to the countless influences on human pathophysiology, including cancer. Research on cancer and anticancer therapy is constantly looking for new hints to improve the response to therapy while reducing the risk of relapse. In this scenario, the gut microbiome and the plethora of microbial-derived metabolites are considered a new opening in the development of innovative anticancer treatments for a better prognosis. This narrative review summarizes the current knowledge on the role of the gut microbiome in the onset and progression of cancer, as well as in response to chemo-immunotherapy. Recent findings regarding the tumor microbiome and its implications for clinical practice are also commented on. Current microbiome-based intervention strategies (i.e., prebiotics, probiotics, live biotherapeutics and fecal microbiota transplantation) are then discussed, along with key shortcomings, including a lack of long-term safety information in patients who are already severely compromised by standard treatments. The implementation of bioinformatic tools applied to microbiomics and other omics data, such as machine learning, has an enormous potential to push research in the field, enabling the prediction of health risk and therapeutic outcomes, for a truly personalized precision medicine.}, }
@article {pmid34544375, year = {2021}, author = {Koo, H and Morrow, CD}, title = {Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {251}, pmid = {34544375}, issn = {1471-2180}, mesh = {Clostridium Infections/*prevention & control ; Fecal Microbiota Transplantation/*methods/standards ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics/*physiology ; Humans ; Immunotherapy/*adverse effects ; Longitudinal Studies ; Melanoma/immunology/therapy ; *Symbiosis ; }, abstract = {BACKGROUND: To understand inter-individual variability of fecal microbe transplantation (FMT) to enhance anti-PD-1 immunotherapy (IT) for melanoma, we analyzed the data sets from two recent publications with a microbial strain-tracking tool to determine if donor strains were dominant in the recipient feces following FMT.
RESULTS: Analysis of the Baruch et al. data set found that the presence of commensal donor microbes in recipient feces post-FMT did not correlate with the patient response to IT. From the Davar et al., data set, we found 4 patients that responded to IT had donor's related strain post-FMT, while 2 patients that did not respond to the IT also had donor's strain post-FMT. Importantly, we identified no donor microbes in the feces in one recipient post-FMT that responded to IT. Furthermore, in depth analysis from two patients who responded to IT revealed both donor and recipient strains at different times post-FMT. Colonization of the gastrointestinal tract niches is important for the interaction with the host immune system. Using a separate data set, we show that mucosa from the cecum, transverse colon, and sigmoid colon share strains, providing a large reservoir of niches containing recipient microbes.
CONCLUSIONS: We demonstrated using strain-tracking analysis individual variation with the respect to the presence of fecal dominant donor microbes in the recipient following FMT that did not correlate with the response to anti-PD-1 immunotherapy. The inter-individual differences of FMT to enhance IT might be explained by the variability of the donor microbes to occupy and outcompete recipient microbes for the gastrointestinal niches. The result from our study supports the use of new approaches to clear the niches in the gastrointestinal tract to promote donor colonization to reduce inter-individual variability of IT for melanoma and potentially other cancers.}, }
@article {pmid34392792, year = {2021}, author = {Han, X and Wang, Y and Zhang, P and Zhu, M and Li, L and Mao, X and Sha, X and Li, L}, title = {Kazak faecal microbiota transplantation induces short-chain fatty acids that promote glucagon-like peptide-1 secretion by regulating gut microbiota in db/db mice.}, journal = {Pharmaceutical biology}, volume = {59}, number = {1}, pages = {1077-1087}, pmid = {34392792}, issn = {1744-5116}, mesh = {Animals ; Bacteroides/isolation & purification ; Diabetes Mellitus, Experimental/physiopathology/*therapy ; Diabetes Mellitus, Type 2/physiopathology/*therapy ; Fatty Acids, Volatile/*metabolism ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Glucagon-Like Peptide 1/metabolism ; Glucose Tolerance Test ; Glycolipids/metabolism ; Humans ; Mice ; RNA, Ribosomal, 16S ; Receptors, G-Protein-Coupled/metabolism ; }, abstract = {CONTEXT: Faecal microbiota transplantation (FMT) from Kazak individuals with normal glucose tolerance (KNGT) significantly reduces plasma glycolipid levels in type 2 diabetes mellitus db/db mice. However, the mechanism behind this effect has not been reported.
OBJECTIVE: To study the mechanism of improved glycolipid disorders in db/db mice by FMT from a KNGT donor.
MATERIALS AND METHODS: The normal diet group consisted of db/m mice orally administered 0.2 mL phosphate buffer saline (PBS) (db/m + PBS). For the db/db + PBS (Vehicle) and db/db + KNGT (FMT intervention group) groups, db/db mice received oral 0.2 mL PBS or faecal microorganisms from a KNGT donor, respectively. All mice were treated daily for 0, 6 or 10 weeks. Faecal DNA samples were sequenced and quantified using 16S rRNA gene sequencing and RT-qPCR, respectively. Short-chain fatty acid (SCFA) levels in the mouse faeces were determined by gas chromatography. G protein-coupled receptor 43 (GPR43) and glucagon-like peptide-1 (GLP-1) expression levels were determined.
RESULTS: FMT intervention significantly increased the relative abundance of Bacteroides uniformis (0.038%, p < 0.05). Clostridium levels (LogSQ) were increased (p < 0.01), while Mucispirillum schaedleri levels (LogSQ) were decreased (p < 0.01). Acetate and butyrate levels in the faeces were significantly increased (acetate; butyrate: 22.68 ± 1.82 mmol/L; 4.13 ± 1.09 mmol/L, p < 0.05). GPR43 mRNA expression and GLP-1 protein expression increased in colon tissue (p < 0.05).
DISCUSSION AND CONCLUSIONS: Mechanistically, FMT-KNGT could improve glycolipid disorders by changing the bacterial composition responsible for producing SCFAs and activating the GPR43/GLP-1 pathway.}, }
@article {pmid34985651, year = {2022}, author = {Szychowiak, P and Villageois-Tran, K and Patrier, J and Timsit, JF and Ruppé, É}, title = {The role of the microbiota in the management of intensive care patients.}, journal = {Annals of intensive care}, volume = {12}, number = {1}, pages = {3}, pmid = {34985651}, issn = {2110-5820}, abstract = {The composition of the gut microbiota is highly dynamic and changes according to various conditions. The gut microbiota mainly includes difficult-to-cultivate anaerobic bacteria, hence knowledge about its composition has significantly arisen from culture-independent methods based on next-generation sequencing (NGS) such as 16S profiling and shotgun metagenomics. The gut microbiota of patients hospitalized in intensive care units (ICU) undergoes many alterations because of critical illness, antibiotics, and other ICU-specific medications. It is then characterized by lower richness and diversity, and dominated by opportunistic pathogens such as Clostridioides difficile and multidrug-resistant bacteria. These alterations are associated with an increased risk of infectious complications or death. Specifically, at the time of writing, it appears possible to identify distinct microbiota patterns associated with severity or infectivity in COVID-19 patients, paving the way for the potential use of dysbiosis markers to predict patient outcomes. Correcting the microbiota disturbances to avoid their consequences is now possible. Fecal microbiota transplantation is recommended in recurrent C. difficile infections and microbiota-protecting treatments such as antibiotic inactivators are currently being developed. The growing interest in the microbiota and microbiota-associated therapies suggests that the control of the dysbiosis could be a key factor in the management of critically ill patients. The present narrative review aims to provide a synthetic overview of microbiota, from healthy individuals to critically ill patients. After an introduction to the different techniques used for studying the microbiota, we review the determinants involved in the alteration of the microbiota in ICU patients and the latter's consequences. Last, we assess the means to prevent or correct microbiota alteration.}, }
@article {pmid34985325, year = {2022}, author = {Sorboni, SG and Moghaddam, HS and Jafarzadeh-Esfehani, R and Soleimanpour, S}, title = {A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders.}, journal = {Clinical microbiology reviews}, volume = {}, number = {}, pages = {e0033820}, doi = {10.1128/CMR.00338-20}, pmid = {34985325}, issn = {1098-6618}, abstract = {The human body is full of an extensive number of commensal microbes, consisting of bacteria, viruses, and fungi, collectively termed the human microbiome. The initial acquisition of microbiota occurs from both the external and maternal environments, and the vast majority of them colonize the gastrointestinal tract (GIT). These microbial communities play a central role in the maturation and development of the immune system, the central nervous system, and the GIT system and are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental factors, lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect the composition of the gut microbiota. Recent publications have highlighted that an imbalance in the gut microflora, known as dysbiosis, is associated with the onset and progression of neurological disorders. Moreover, characterization of the microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical and clinical research on interventions related to the gut microbiome for treating neurological conditions, including autism spectrum disorders, Parkinson's disease, schizophrenia, multiple sclerosis, Alzheimer's disease, epilepsy, and stroke, hold significant promise. This review aims to present a comprehensive overview of the potential involvement of the human gut microbiome in the pathogenesis of neurological disorders, with a particular emphasis on the potential of microbe-based therapies and/or diagnostic microbial biomarkers. This review also discusses the potential health benefits of the administration of probiotics, prebiotics, postbiotics, and synbiotics and fecal microbiota transplantation in neurological disorders.}, }
@article {pmid34980687, year = {2022}, author = {Gweon, TG and Lee, YJ and Kim, KO and Yim, SK and Soh, JS and Kim, SY and Park, JJ and Shin, SY and Lee, TH and Choi, CH and Cho, YS and Yong, D and Chung, JW and Lee, KJ and Lee, OY and Choi, MG and Choi, M and , }, title = {Clinical Practice Guidelines for Fecal Microbiota Transplantation in Korea.}, journal = {Journal of neurogastroenterology and motility}, volume = {28}, number = {1}, pages = {28-42}, doi = {10.5056/jnm21221}, pmid = {34980687}, issn = {2093-0879}, abstract = {Fecal microbiota transplantation (FMT) is a highly efficacious and safe modality for the treatment of recurrent or refractory Clostridioides difficile infection (CDI), with overall success rates of 90%. Thus, FMT has been widely used for 10 years. The incidence and clinical characteristics of CDI, the main indication for FMT, differ between countries. To date, several guidelines have been published. However, most of them were published in Western countries and therefore cannot represent the Korean national healthcare systems. One of the barriers to performing FMT is a lack of national guidelines. Accordingly, multidisciplinary experts in this field have developed practical guidelines for FMT. The purpose of these guidelines is to aid physicians performing FMT, which can be adapted to treat CDI and other conditions.}, }
@article {pmid34980222, year = {2022}, author = {Chen, Y and Liu, Y and Wang, Y and Chen, X and Wang, C and Chen, X and Yuan, X and Liu, L and Yang, J and Zhou, X}, title = {Prevotellaceae produces butyrate to alleviate PD-1/PD-L1 inhibitor-related cardiotoxicity via PPARα-CYP4X1 axis in colonic macrophages.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {41}, number = {1}, pages = {1}, pmid = {34980222}, issn = {1756-9966}, abstract = {BACKGROUND: Immune checkpoint inhibitor-related cardiotoxicity is one of the most lethal adverse effects, and thus, the identification of underlying mechanisms for developing strategies to overcome it has clinical importance. This study aimed to investigate whether microbiota-host interactions contribute to PD-1/PD-L1 inhibitor-related cardiotoxicity.
METHODS: A mouse model of immune checkpoint inhibitor-related cardiotoxicity was constructed by PD-1/PD-L1 inhibitor BMS-1 (5 and 10 mg/kg), and cardiomyocyte apoptosis and cardiotoxicity were determined by hematoxylin and eosin, Masson's trichome and TUNEL assays. 16S rRNA sequencing was used to define the gut microbiota composition. Gut microbiota metabolites short-chain fatty acids (SCFAs) were determined by HPLC. The serum levels of myocardial enzymes (creatine kinase, aspartate transaminase, creatine kinase-MB and lactate dehydrogenase) and the production of M1 factors (TNF-α and IL-1β) were measured by ELISA. The colonic macrophage phenotype was measured by mmunofluorescence and qPCR. The expression of Claudin-1, Occludin, ZO-1 and p-p65 was measured by western blot. The gene expression of peroxisome proliferator-activated receptor α (PPARα) and cytochrome P450 (CYP) 4X1 was determined using qPCR. Statistical analyses were performed using Student's t-test for two-group comparisons, and one-way ANOVA followed by Student-Newman-Keul test for multiple-group comparisons.
RESULTS: We observed intestinal barrier injury and gut microbiota dysbiosis characterized by Prevotellaceae and Rikenellaceae genus depletion and Escherichia-Shigella and Ruminococcaceae genus enrichment, accompanied by low butyrate production and M1-like polarization of colonic macrophages in BMS-1 (5 and 10 mg/kg)-induced cardiotoxicity. Fecal microbiota transplantation mirrored the effect of BMS-1 on cardiomyocyte apoptosis and cardiotoxicity, while macrophage depletion and neutralization of TNF-α and IL-1β greatly attenuated BMS-1-induced cardiotoxicity. Importantly, Prevotella loescheii recolonization and butyrate supplementation alleviated PD-1/PD-L1 inhibitor-related cardiotoxicity. Mechanistically, gut microbiota dysbiosis promoted M1-like polarization of colonic macrophages and the production of proinflammatory factors TNF-α and IL-1β through downregulation of PPARα-CYP4X1 axis.
CONCLUSIONS: Intestinal barrier dysfunction amplifies PD-1/PD-L1 inhibitor-related cardiotoxicity by upregulating proinflammatory factors TNF-α and IL-1β in colonic macrophages via downregulation of butyrate-PPARα-CYP4X1 axis. Thus, targeting gut microbiota to polarize colonic macrophages away from the M1-like phenotype could provide a potential therapeutic strategy for PD-1/PD-L1 inhibitor-related cardiotoxicity.}, }
@article {pmid34977119, year = {2021}, author = {Pan, B and Liu, X and Shi, J and Chen, Y and Xu, Z and Shi, D and Ruan, G and Wang, F and Huang, Y and Xu, C}, title = {A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {775216}, doi = {10.3389/fnut.2021.775216}, pmid = {34977119}, issn = {2296-861X}, abstract = {Background and aims: Metabolic syndrome (MetS), accompanied with significant intestinal dysbiosis, causes a great public health burden to human society. Here, we carried out a meta-analysis to qualify randomized controlled trials (RCTs) and to systematically evaluate the effect of microbial therapy on MetS. Methods and results: Forty-two RCTs were eligible for this meta-analysis after searching the PubMed, Cochrane, and Embase databases. Pooled estimates demonstrated that treatment with microbial therapy significantly reduced the waist circumference (WC) (SMD = -0.26, 95% CI -0.49, -0.03), fasting blood glucose (FBG) (SMD = -0.35, 95% CI -0.52, -0.18), total cholesterol (TC) (SMD = -0.36, 95% CI -0.55, -0.17), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.42, 95% CI -0.61, -0.22), and triacylglycerol (TG)(SMD = -0.38, 95% CI -0.55, -0.20), but increased the high-density lipoprotein cholesterol (HDL-C) (SMD = 0.28, 95% CI.03, 0.52). Sensitivity analysis indicated that after eliminating one study utilizing Bifidobacteriumlactis, results became statistically significant in diastolic blood pressure (DBP) (SMD = -0.24, 95% CI -0.41, -0.07) and in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (SMD = -0.28, 95% CI -0.54, -0.03), while the body mass index (BMI) showed significant difference after eliminating one study utilizing oat bran (SMD = -0.16, 95% CI -0.31, -0.01). There was still no significant effect in systolic blood pressure (SBP) and in hemoglobin A1c (HbA1c%). Conclusion: In patients with MetS, the conditioning with microbial therapy notably improves FBG, TC, TG, HDL-C, LDL-C, WC, BMI (except for the study using oat bran), HOMA-IR, and DBP (except for the Study using Bifidobacteriumlactis), however, with no effect in SBP and in HbA1c%.}, }
@article {pmid34976874, year = {2021}, author = {Li, S and Wei, J and Chen, T}, title = {Editorial: Gut Microbiota in the Occurrence, Development and Treatment of Gut-Brain Disorders.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {808454}, doi = {10.3389/fcimb.2021.808454}, pmid = {34976874}, issn = {2235-2988}, }
@article {pmid34975748, year = {2021}, author = {Ye, X and Liu, Y and Hu, J and Gao, Y and Ma, Y and Wen, D}, title = {Chlorogenic Acid-Induced Gut Microbiota Improves Metabolic Endotoxemia.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {762691}, doi = {10.3389/fendo.2021.762691}, pmid = {34975748}, issn = {1664-2392}, abstract = {Background: Coffee can regulate glucose homeostasis but the underlying mechanism is unclear. This study investigated the preventive and therapeutic effects of chlorogenic acid (CGA), a polyphenol that is found in coffee, on obesity and obesity-related metabolic endotoxemia.
Method: Male 4-week-old C57BL/6 mice were fed either normal chow or a high-fat diet or 20 weeks and half the mice in each group were gavaged with CGA. Oral glucose tolerance tests (OGTTs) and insulin tolerance tests (ITTs) were performed. Markers of inflammation and intestinal barrier function were assayed. The composition of the gut microbiota was analyzed by 16S rRNA high-throughput pyrosequencing. The role of CGA-altered microbiota in metabolic endotoxemia was verified by fecal microbiota transplantation.
Results: CGA protected against HFD-induced weight gain, decreased the relative weight of subcutaneous and visceral adipose, improved intestinal barrier integrity, and prevented glucose metabolic disorders and endotoxemia (P <0.05). CGA significantly changed the composition of the gut microbiota and increased the abundance of short chain fatty acid (SCFA)-producers (e.g., Dubosiella, Romboutsia, Mucispirillum, and Faecalibaculum) and Akkermansia, which can protect the intestinal barrier. In addition, mice with the CGA-altered microbiota had decreased body weight and fat content and inhibited metabolic endotoxemia.
Conclusion: CGA-induced changes in the gut microbiota played an important role in the inhibition of metabolic endotoxemia in HFD-fed mice.}, }
@article {pmid34970262, year = {2021}, author = {Gao, G and Ma, T and Zhang, T and Jin, H and Li, Y and Kwok, LY and Zhang, H and Sun, Z}, title = {Adjunctive Probiotic Lactobacillus rhamnosus Probio-M9 Administration Enhances the Effect of Anti-PD-1 Antitumor Therapy via Restoring Antibiotic-Disrupted Gut Microbiota.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {772532}, pmid = {34970262}, issn = {1664-3224}, abstract = {Emerging evidence supports that the efficacy of immune checkpoint blockade (ICB) therapy is associated with the host's gut microbiota, as prior antibiotic intake often leads to poor outcome and low responsiveness toward ICB treatment. Therefore, we hypothesized that the efficacy of ICB therapy like anti-programmed cell death protein-1 (PD-1) treatment required an intact host gut microbiota, and it was established that probiotics could enhance the recovery of gut microbiota disruption by external stimuli. Thus, the present study aimed to evaluate the effect of the probiotics, Lactobacillus rhamnosus Probio-M9, on recovering antibiotic-disrupted gut microbiota and its impact on the outcome of ICB therapy in tumor-bearing mice. We first disrupted the mouse microbiota by antibiotics and then remediated the gut microbiota by probiotics or naturally. Tumor transplantation was then performed, followed by anti-PD-1-based antitumor therapy. Changes in the fecal metagenomes and the tumor suppression effect were monitored during different stages of the experiment. Our results showed that Probio-M9 synergized with ICB therapy, significantly improving tumor inhibition compared with groups not receiving the probiotic treatment (P < 0.05 at most time points). The synergistic effect was accompanied by effective restoration of antibiotic-disrupted fecal microbiome that was characterized by a drastically reduced Shannon diversity value and shifted composition of dominating taxa. Moreover, probiotic administration significantly increased the relative abundance of beneficial bacteria (e.g., Bifidobacterium pseudolongum, Parabacteroides distasonis, and some Bacteroides species; 0.0001 < P < 0.05). The gut microbiome changes were accompanied by mild reshaping of the functional metagenomes characterized by enrichment in sugar degradation and vitamin and amino acid synthesis pathways. Collectively, this study supported that probiotic administration could enhance the efficacy and responsiveness of anti-PD-1-based immunotherapy, and Probio-M9 could be a potential candidate of microbe-based synergistic tumor therapeutics. The preclinical data obtained here would support the design of future human clinical trials for further consolidating the current findings and for safety assessment of probiotic adjunctive treatment in ICB therapy.}, }
@article {pmid34590904, year = {2021}, author = {Vuyyuru, SK and Kedia, S and Kalaivani, M and Sahu, P and Kante, B and Kumar, P and Ranjan, MK and Makharia, G and Ananthakrishnan, A and Ahuja, V}, title = {Efficacy and safety of fecal transplantation versus targeted therapies in ulcerative colitis: network meta-analysis.}, journal = {Future microbiology}, volume = {16}, number = {}, pages = {1215-1227}, doi = {10.2217/fmb-2020-0242}, pmid = {34590904}, issn = {1746-0921}, mesh = {Adalimumab/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; *Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation ; Humans ; Network Meta-Analysis ; Randomized Controlled Trials as Topic ; }, abstract = {Aim: We conducted this network meta-analysis to compare the efficacy and safety of targeted pharmacotherapies and fecal microbial transplantation (FMT). Patients & methods: Nineteen studies were included and there was only one head-to-head randomized controlled trial (adalimumab vs vedolizumab). Results: All interventions, including FMT, were superior to a placebo in inducing clinical remission (except adalimumab - odds ratio 1.66; 95% CI: 0.97-2.85), clinical response and endoscopic remission. FMT was comparable with other agents in achieving all efficacy outcomes. Infliximab was ranked highest in inducing clinical remission (surface under the cumulative ranking, 0.8). There was no difference in safety outcomes between FMT and other targeted therapies. Conclusion: FMT is as efficacious and as safe as other targeted therapies in inducing clinical remission, clinical response and endoscopic remission. Further studies to assess the long-term benefits are needed in order to reach a definitive conclusion.}, }
@article {pmid34363822, year = {2021}, author = {Zheng, W and Duan, M and Jia, J and Song, S and Ai, C}, title = {Low-molecular alginate improved diet-induced obesity and metabolic syndrome through modulating the gut microbiota in BALB/c mice.}, journal = {International journal of biological macromolecules}, volume = {187}, number = {}, pages = {811-820}, doi = {10.1016/j.ijbiomac.2021.08.003}, pmid = {34363822}, issn = {1879-0003}, mesh = {Adiposity ; *Alginates ; Animal Feed ; Animals ; Bacteria/*metabolism ; Biomarkers/blood ; Diet, High-Fat ; Disease Models, Animal ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Inflammation Mediators/metabolism ; Lipids/blood ; Male ; Metabolic Syndrome/blood/*diet therapy/microbiology ; Mice, Inbred BALB C ; Molecular Weight ; Obesity/blood/*diet therapy/microbiology ; *Prebiotics ; Weight Gain ; }, abstract = {Alginate is the most abundant polysaccharide in brown seaweed, which is widely used as a food additive, but its high viscosity and gel property limit its applications in foods as a functional ingredient. In this study, low-molecular alginate from Laminaria japonica (L-LJA) was prepared, and its effect on obesity and metabolic syndrome was analyzed in high-fat diet (HFD)-fed mice. L-LJA reduced weight gain, fat accumulation in the liver and epididymal adipose tissue, lipid abnormality and inflammation in HFD-fed mice accompanied with the improvement of gut microbiota. L-LJA modulated the structure of gut microbiota, increased some Bacteroidales members, and reduced some Clostridiales members in mice, which were positively correlated with the improvement of physiological status. Fecal transplant from L-LJA-fed mice reduced fat accumulation in body tissues and lipid abnormality in the serum and liver and increased short chain fatty acids production in HFD-fed mice, confirming that L-LJA-induced gut microbiota alteration played an important role in its bioactivity. L-LJA has better solubility and can be utilized in food systems in high dose, implying that it can be developed as a prebiotic agent to increase both economic value and nutritive value of alginate.}, }
@article {pmid34224741, year = {2021}, author = {Khoruts, A}, title = {Can FMT Cause or Prevent CRC? Maybe, But There Is More to Consider.}, journal = {Gastroenterology}, volume = {161}, number = {4}, pages = {1103-1105}, doi = {10.1053/j.gastro.2021.06.074}, pmid = {34224741}, issn = {1528-0012}, mesh = {*Clostridioides difficile ; *Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid34966755, year = {2021}, author = {Hu, Y and Ye, Z and Wu, M and She, Y and Li, L and Xu, Y and Qin, K and Hu, Z and Yang, M and Lu, F and Ye, Q}, title = {The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {766126}, doi = {10.3389/fmed.2021.766126}, pmid = {34966755}, issn = {2296-858X}, abstract = {Ulcerative Colitis (UC) is a chronic inflammatory bowel disease. The prolonged course of UC and the lack of effective treatment management make it difficult to cure, affecting the health and life safety of patients. Although UC has received more attention, the etiology and pathogenesis of UC are still unclear. Therefore, it is urgent to establish an updated and comprehensive understanding of UC and explore effective treatment strategies. Notably, sufficient evidence shows that the intestinal microbiota plays an important role in the pathogenesis of UC, and the treating method aimed at improving the balance of the intestinal microbiota exhibits a therapeutic potential for UC. This article reviews the relationship between the genetic, immunological and microbial risk factors with UC. At the same time, the UC animal models related to intestinal microbiota dysbiosis induced by chemical drugs were evaluated. Finally, the potential value of the therapeutic strategies for restoring intestinal microbial homeostasis and treating UC were also investigated. Comprehensively, this study may help to carry out preclinical research, treatment theory and methods, and health management strategy of UC, and provide some theoretical basis for TCM in the treatment of UC.}, }
@article {pmid34965174, year = {2022}, author = {Hiippala, K and Khan, I and Ronkainen, A and Boulund, F and Vähä-Mäkilä, H and Suutarinen, M and Seifert, M and Engstrand, L and Satokari, R}, title = {Novel strain of Pseudoruminococcus massiliensis possesses traits important in gut adaptation and host-microbe interactions.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2013761}, doi = {10.1080/19490976.2021.2013761}, pmid = {34965174}, issn = {1949-0984}, abstract = {Fecal microbiota transplantation (FMT) is an efficient treatment for recurrent Clostridioides difficile infection and currently investigated as a treatment for other intestinal and systemic diseases. Better understanding of the species potentially transferred in FMT is needed. We isolated from a healthy fecal donor a novel strain E10-96H of Pseudoruminococcus massiliensis, a recently described strictly anaerobic species currently represented only by the type strain. The whole genome sequence of E10-96H had over 98% similarity with the type strain. E10-96H carries 20 glycoside hydrolase encoding genes, degrades starch in vitro and thus may contribute to fiber degradation, cross-feeding of other species and butyrate production in the intestinal ecosystem. The strain carries pilus-like structures, harbors pilin genes in its genome and adheres to enterocytes in vitro but does not provoke a proinflammatory response. P. massiliensis seems to have commensal behavior with the host epithelium, and its role in intestinal ecology should be studied further.}, }
@article {pmid34963452, year = {2021}, author = {Lin, H and Guo, Q and Wen, Z and Tan, S and Chen, J and Lin, L and Chen, P and He, J and Wen, J and Chen, Y}, title = {The multiple effects of fecal microbiota transplantation on diarrhea-predominant irritable bowel syndrome (IBS-D) patients with anxiety and depression behaviors.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {233}, pmid = {34963452}, issn = {1475-2859}, support = {No. 81770529//National Natural Science Foundation of China/ ; No. 82070543//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Anxiety and depression are complications in Irritable bowel syndrome (IBS) patients. In this study, we recruited 18 IBS patients with mild-modest anxiety and depression behaviors, and after the screening, we defined the FMT treatment group (n = 9) and the control group (n = 9). The IBS symptom severity scale (IBS-SSS), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), Irritable Bowel Syndrome Quality of Life (IBS-QOL) and Bristol stool scale (BSS) were evaluated one week before FMT (baseline), one-week-, one-month-, two-month-, and three-month-following FMT. Meanwhile, we determined the SCFAs in the patient's feces and serum and continued the metagenomic analysis of the microorganisms in the patient's feces.
RESULTS: The results showed that the patient's anxiety and depression behavior gradually improved with FMT treatment. Moreover, the illness and quality of life had also been relieved significantly. The content of isovaleric acid and valeric acid was significantly reduced in the FMT group compared to the Col group. Metagenomic analysis showed that FMT treatment decreased the abundance of Faecalibacterium, Eubacterium and Escherichia. From KEGG functional analysis, we confirmed that the top five abundant pathways were "bacterial chemotaxis, "flagellar assembly", "glycine, serine and threonine metabolism", "apoptosis", and "bacterial invasion of epithelial cells".
CONCLUSIONS: FMT treatment can effectively alleviate the anxiety and depression behaviors of IBS-D patients and reduce the IBS-SSS score, indicating that FMT can improve patients' symptoms. The high throughput sequencing results show that Bifidobacterium and Escherichia play the most critical role in the formation and recovery of IBS-D patients. The GC/MS data indicated that faeces isovaleric acid and valeric acid might be more suitable as a metabolic indicator of IBS-D remission. Trial registration ChiCTR, ChiCTR1900024924, Registered 3 August 2019, https://www.chictr.org.cn/showproj.aspx?proj=41676 .}, }
@article {pmid34898421, year = {2021}, author = {Tu, T and Zhao, C}, title = {Treating autism spectrum disorder by intervening with gut microbiota.}, journal = {Journal of medical microbiology}, volume = {70}, number = {12}, pages = {}, doi = {10.1099/jmm.0.001469}, pmid = {34898421}, issn = {1473-5644}, mesh = {*Autism Spectrum Disorder/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; }, abstract = {Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders with a high prevalence in childhood. The gut microbiota can affect human cognition and moods and has a strong correlation with ASD. Microbiota transplantation, including faecal microbiota transplantation (FMT), probiotics, breastfeeding, formula feeding, gluten-free and casein-free (GFCF) diet and ketogenic diet therapy, may provide satisfying effects for ASD and its related various symptoms. For instance, FMT can improve the core symptoms of ASD and gastrointestinal symptoms. Probiotics, breastfeeding and formula feeding, and GFCF diet can improve gastrointestinal symptoms. The core symptom score still needs to be confirmed by large-scale clinical randomized controlled studies. It is recommended to use a ketogenic diet to treat patients with epilepsy in ASD. At present, the unresolved problems include which of gut the microbiota are beneficial, which of the microorganisms are harmful, how to safely and effectively implant beneficial bacteria into the human body, and how to extract and eliminate harmful microorganisms before transplantation. In future studies, large sample and randomized controlled clinical studies are needed to confirm the mechanism of intestinal microorganisms in the treatment of ASD and the method of microbial transplantation.}, }
@article {pmid34962114, year = {2021}, author = {Jang, S and Kim, Y and Lee, C and Kwon, B and Noh, J and Jee, JJ and Yoon, SS and Koh, H and Park, S}, title = {The Effect of Formula-based Nutritional Treatment on Colitis in a Murine Model.}, journal = {Journal of Korean medical science}, volume = {36}, number = {50}, pages = {e342}, doi = {10.3346/jkms.2021.36.e342}, pmid = {34962114}, issn = {1598-6357}, support = {//Korea Health Industry Development Institute/Korea ; }, abstract = {BACKGROUND: Exclusive enteral nutrition (EEN) induces remission in pediatric Crohn's disease (CD). The exact mechanism of EEN therapy in CD is unknown, but alteration of the intestinal microflora after EEN is thought to affect mucosal healing. To determine the link between EEN therapy and therapeutic efficacy in CD, we established a murine model of dextran sulfate sodium (DSS)-induced colitis and applied EEN therapy.
METHODS: Eight-week-old C57BL/6 mice were administered DSS for 4 days to induce colitis, and either normal chow (NC) or EEN was administered for the following 4 days. The mice were grouped according to the feeding pattern after DSS administration: DSS/NC and DSS/EEN groups. The clinical course was confirmed via daily observation of the weight and stool. Fecal samples were collected and 16sRNA sequencing was used. The mice were sacrificed to confirm colonic histopathology.
RESULTS: Weight reduction and increase in disease activity were observed as the day progressed for 4 days after DSS administration. There was significant weight recovery and improvement in disease activity in the EEN group compared to that in the NC group. Verrucomicrobia and Proteobacteria abundances tended to increase and Bacteroidetes abundance decreased in the EEN group. In the EEN group, significant changes in the β-diversity of the microbiota were observed. In the analysis of microbiome species, abundances of Akkermansia muciniphila, Clostridium cocleatum, mucin-degrading bacteria, Flintibacter butyricus, and Parabacteroides goldsteinii, which are beneficial microbiota, were significantly increased in the EEN group compared to those in the NC group. More abundant mucins were confirmed in the colonic histopathology of the EEN group. These microbial and histopathological differences suggested that EEN might improve colitis symptoms in a murine colitis model by promoting mucin recycling and subsequently inducing the healing effect of the gut barrier.
CONCLUSION: EEN showed clinical efficacy in a murine model of colitis. Based on the increase in mucin-degrading bacteria and the pathological increase in mucin production after EEN administration, it can be observed that mucin plays an important role in the therapeutic effect of EEN.}, }
@article {pmid34960049, year = {2021}, author = {Chernikova, MA and Flores, GD and Kilroy, E and Labus, JS and Mayer, EA and Aziz-Zadeh, L}, title = {The Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/nu13124497}, pmid = {34960049}, issn = {2072-6643}, support = {AR170062//United States Department of Defense/ ; }, abstract = {Gastrointestinal dysfunction is one of the most prevalent physiological symptoms of autism spectrum disorder (ASD). A growing body of largely preclinical research suggests that dysbiotic gut microbiota may modulate brain function and social behavior, yet little is known about the mechanisms that underlie these relationships and how they may influence the pathogenesis or severity of ASD. While various genetic and environmental risk factors have been implicated in ASD, this review aims to provide an overview of studies elucidating the mechanisms by which gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development, in at least a subgroup of individuals with gastrointestinal problems. Specifically, we review the brain-gut-microbiome system and discuss findings from current animal and human studies as they relate to social-behavioral and neurological impairments in ASD, microbiota-targeted therapies (i.e., probiotics, fecal microbiota transplantation) in ASD, and how microbiota may influence the brain at molecular, structural, and functional levels, with a particular interest in social and emotion-related brain networks. A deeper understanding of microbiome-brain-behavior interactions has the potential to inform new therapies aimed at modulating this system and alleviating both behavioral and physiological symptomatology in individuals with ASD.}, }
@article {pmid34959977, year = {2021}, author = {Sobocki, BK and Kaźmierczak-Siedlecka, K and Folwarski, M and Hawryłkowicz, V and Makarewicz, W and Stachowska, E}, title = {Pancreatic Cancer and Gut Microbiome-Related Aspects: A Comprehensive Review and Dietary Recommendations.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/nu13124425}, pmid = {34959977}, issn = {2072-6643}, abstract = {Gut microbiota plays a significant role in the human body providing many beneficial effects on the host. However, its dysbiotic alterations may affect the tumorigenic pathway and then trigger the development of pancreatic cancer. This dysbiosis can also modulate the aggressiveness of the tumor, influencing the microenvironment. Because pancreatic cancer is still one of the most lethal cancers worldwide with surgery as the only method that influences prognosis and has curative potential, there is a need to search for other strategies which will enhance the efficiency of standard therapy and improve patients' quality of life. The administration of prebiotics, probiotics, next-generation probiotics (Faecalibacterium prausnitzii, Akkermansia muciniphila), synbiotics, postbiotics, and fecal microbiota transplantation through multiple mechanisms affects the composition of the gut microbiota and may restore its balance. Despite limited data, some studies indicate that the aforementioned methods may allow to achieve better effect of pancreatic cancer treatment and improve therapeutic strategies for pancreatic cancer patients.}, }
@article {pmid34959505, year = {2021}, author = {Pane, S and Ristori, MV and Gardini, S and Russo, A and Del Chierico, F and Putignani, L}, title = {Clinical Parasitology and Parasitome Maps as Old and New Tools to Improve Clinical Microbiomics.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, doi = {10.3390/pathogens10121550}, pmid = {34959505}, issn = {2076-0817}, support = {Ricerca Corrente 2020 and 2021//Italian Ministry of Health/ ; }, abstract = {A growing body of evidence shows that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, which reduces host damage. Herein, we discuss how diagnostic parasitology may contribute to designing clinical metagenomic pipelines and FMT programs, especially in pediatric subjects. The consequences of more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.}, }
@article {pmid33825149, year = {2021}, author = {Liang, Y and Cui, L and Gao, J and Zhu, M and Zhang, Y and Zhang, HL}, title = {Gut Microbial Metabolites in Parkinson's Disease: Implications of Mitochondrial Dysfunction in the Pathogenesis and Treatment.}, journal = {Molecular neurobiology}, volume = {58}, number = {8}, pages = {3745-3758}, pmid = {33825149}, issn = {1559-1182}, support = {81974194//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Brain/*metabolism ; Brain-Gut Axis/*physiology ; Dysbiosis/genetics/metabolism/therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Mitochondria/genetics/*metabolism ; Parkinson Disease/genetics/*metabolism/*therapy ; Probiotics/therapeutic use ; Treatment Outcome ; Ubiquitin-Protein Ligases/genetics/metabolism ; }, abstract = {The search for therapeutic targets for Parkinson's disease (PD) is hindered by the incomplete understanding of the pathophysiology of the disease. Mitochondrial dysfunction is an area with high potential. The neurobiological signaling connections between the gut microbiome and the central nervous system are incompletely understood. Multiple lines of evidence suggest that the gut microbiota participates in the pathogenesis of PD. Gut microbial dysbiosis may contribute to the loss of dopaminergic neurons through mitochondrial dysfunction. The intervention of gut microbial metabolites via the microbiota-gut-brain axis may serve as a promising therapeutic strategy for PD. In this narrative review, we summarize the potential roles of gut microbial dysbiosis in PD, with emphasis on microbial metabolites and mitochondrial function. We then review the possible ways in which microbial metabolites affect the central nervous system, as well as the impact of microbial metabolites on mitochondrial dysfunction. We finally discuss the possibility of gut microbiota as a therapeutic target for PD.}, }
@article {pmid34957088, year = {2021}, author = {Bi, C and Xiao, G and Liu, C and Yan, J and Chen, J and Si, W and Zhang, J and Liu, Z}, title = {Molecular Immune Mechanism of Intestinal Microbiota and Their Metabolites in the Occurrence and Development of Liver Cancer.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {702414}, doi = {10.3389/fcell.2021.702414}, pmid = {34957088}, issn = {2296-634X}, abstract = {Intestinal microorganisms are closely associated with immunity, metabolism, and inflammation, and play an important role in health and diseases such as inflammatory bowel disease, diabetes, cardiovascular disease, Parkinson's disease, and cancer. Liver cancer is one of the most fatal cancers in humans. Most of liver cancers are slowly transformed from viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease. However, the relationship between intestinal microbiota and their metabolites, including short-chain fatty acids, bile acids, indoles, and ethanol, and liver cancer remains unclear. Here, we summarize the molecular immune mechanism of intestinal microbiota and their metabolites in the occurrence and development of liver cancer and reveal the important role of the microbiota-gut-liver axis in liver cancer. In addition, we describe how the intestinal flora can be balanced by antibiotics, probiotics, postbiotics, and fecal bacteria transplantation to improve the treatment of liver cancer. This review describes the immunomolecular mechanism of intestinal microbiota and their metabolites in the occurrence and development of hepatic cancer and provides theoretical evidence support for future clinical practice.}, }
@article {pmid34956503, year = {2021}, author = {Zhao, D and Ye, C and Zhang, S and Lv, X and Yang, B}, title = {Analysis of risk factors for early clinical recurrence of inflammatory bowel disease after fecal microbiota transplantation.}, journal = {American journal of translational research}, volume = {13}, number = {11}, pages = {12875-12886}, pmid = {34956503}, issn = {1943-8141}, abstract = {OBJECTIVE: To explore the risk factors for early clinical recurrence of inflammatory bowel disease (IBD) after fecal microbiota transplantation (FMT).
METHODS: A retrospective study was conducted on 192 patients with IBD who received FMT treatment in the Colorectal Disease Specialty/Intestinal Microecology Treatment Center of the Tenth People's Hospital Affiliated to Tongji University from February 2017 to June 2020. Univariate and multivariate logistic regression models were used to analyze the risk factors for early recurrence of inflammation. Feces from all participants were collected to extract the total bacterial genomic DNA. The V6-8 regions of the bacterial 16S rDNA gene were amplified by polymerase chain reaction (PCR), the PCR products were detected by the denaturing gradient gel electrophoresis (DGGE) method, and the intestinal flora was analyzed by DNA fingerprinting. Stool samples from all patients were tested for 9 bacteria, white blood cells (WBC) and platelet (PLT) counts, as well as the erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level.
RESULTS: Of the 192 patients, 15 cases had inflammation recurrence during FMT and within one week after treatment, including 11 cases of ulcerative colitis (UC) and 4 cases of Crohn's disease (CD), with a total recurrence rate of 7.8%. High Mayo inflammatory activity score, Mayo endoscopic sub-item score (MES) =3 points, CRP>10 mg/L, anemia, albumin <30 g/L, absolute value of peripheral blood lymphocytes (PBL) <500/mm3, and intolerance to enteral full nutrition were independent risk factors for recurrence during and after FMT in UC patients (P<0.05). Albumin <30 g/L and simultaneous use of immunosuppressive agents were associated with disease recurrence during and after FMT in CD patients. WBC, PLT, and CRP were all negatively correlated with Enterococcus (EC), and ESR was positively correlated with Saccharomyces boulardii (SB) (P<0.01).
CONCLUSION: The low recurrence rate of IBD after FMT indicates the safety of FMT, but this procedure should be cautiously used in patients with severe intestinal barrier dysfunction and/or severe intestinal dysfunction.}, }
@article {pmid34955896, year = {2021}, author = {Zhao, Z and Guo, Z and Yin, Z and Qiu, Y and Zhou, B}, title = {Gut Microbiota Was Involved in the Process of Liver Injury During Intra-Abdominal Hypertension.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {790182}, doi = {10.3389/fphys.2021.790182}, pmid = {34955896}, issn = {1664-042X}, abstract = {Background: Intestinal damage caused by intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) can lead to the ectopic gut microbiota, which can contribute to liver injury via portal veins. Therefore, it is speculated that gut microbiota disorder caused by IAH/ACS may result in liver injury. The relationship between gut microbiota and IAH/ACS-related liver injury was investigated in this study. Methods: A model of IAH was established in rats, and 16S rRNA sequencing was analyzed for gut microbiota in the feces of rats. The elimination of gut microbiota was completed by antibiotics gavage, and fecal microbiota transplantation (FMT) was used to change the composition of gut microbiota in rats. Results: In addition to the traditional cause of liver blood vessel compression, liver injury caused by IAH was also associated with gut microbiota dysbiosis. Gut microbiota clearance can relieve liver injury caused by IAH, while FMT from IAH-intervened rats can aggravate IAH-related liver injury. Conclusion: The gut microbiota was one of the most important factors contributing to the IAH-related liver injury, and the JNK/p38 signaling pathway was activated in this process.}, }
@article {pmid34955437, year = {2021}, author = {Aira, A and Arajol, C and Casals-Pascual, C and González-Suárez, B and Martí, S and Domínguez, MÁ and Guardiola, J and Soriano, Á and , }, title = {Recommendations for stool donor selection for fecal microbiota transplant. Consensus document endorsed by the Catalan Society of Digestology, Catalan Society of Infectious diseases and Clinical Microbiology and the GEMBIOTA group from Spanish Society of Infectious Diseases and Clinical Microbiology.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.eimce.2021.12.001}, pmid = {34955437}, issn = {2529-993X}, abstract = {Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimise the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluña with the aim of establishing recommendations for the selection of the fecal microbiota donor.}, }
@article {pmid34950432, year = {2021}, author = {Shaikh, DH and Patel, H and Munshi, R and Sun, H and Mehershahi, S and Baiomi, A and Alemam, A and Pirzada, U and Nawaz, I and Naher, K and Hanumanthu, S and Nayudu, S}, title = {Patients with Clostridium difficile infection and prior appendectomy may be prone to worse outcomes.}, journal = {World journal of gastrointestinal surgery}, volume = {13}, number = {11}, pages = {1436-1447}, pmid = {34950432}, issn = {1948-9366}, abstract = {BACKGROUND: Clostridium difficile infection (CDI) occurs due to a dysbiosis in the colon. The appendix is considered a 'safe house' for gut microbiota and may help repopulate gut flora of patients with CDI.
AIM: To study the impact of prior appendectomy on the severity and outcomes of CDI.
METHODS: We retrospectively reviewed data of 1580 patients with CDI, admitted to our hospital between 2008 to 2018. Patients were grouped based on the presence or absence of the appendix. The primary aim was to (1) assess all-cause mortality and (2) the severity of CDI. Severity was defined as per the Infectious Diseases Society of America criteria. Logistic regression, and propensity score analysis using inverse probability of treatment weights (IPTW) was performed.
RESULTS: Of the 1580 patients, 12.5% had a history of appendectomy. There was no statistical difference in mortality between patients with a prior appendectomy or without (13.7% vs 14%, P = 0.877). However, a history of appendectomy affected the severity of CDI [odds ratio (OR) = 1.32, 95% confidence interval: 1.01-1.75]. On IPTW, this association remained significant (OR = 1.59, P < 0.05). On multivariable analysis of secondary outcomes, prior appendectomy was also associated with toxic megacolon (OR = 5.37, P < 0.05) and colectomy (OR = 2.77, P < 0.05).
CONCLUSION: Prior appendectomy may affect the severity of CDI, development of toxic megacolon and the eventual need for colectomy. Since treatment of CDI is governed by its severity, stronger antibiotic regimens or earlier use of fecal microbiota transplant may be a viable option for patients with prior appendectomy.}, }
@article {pmid34950418, year = {2021}, author = {Xu, B and Qin, W and Xu, Y and Yang, W and Chen, Y and Huang, J and Zhao, J and Ma, L}, title = {Dietary Quercetin Supplementation Attenuates Diarrhea and Intestinal Damage by Regulating Gut Microbiota in Weanling Piglets.}, journal = {Oxidative medicine and cellular longevity}, volume = {2021}, number = {}, pages = {6221012}, pmid = {34950418}, issn = {1942-0994}, abstract = {Antioxidant polyphenols from plants are potential dietary supplementation to alleviate early weaning-induced intestinal disorders in piglets. Recent evidences showed polyphenol quercetin could reshape gut microbiota when it functioned as anti-inflammation or antioxidation agents in rodent models. However, the effect of dietary quercetin supplementation on intestinal disorders and gut microbiota of weanling piglets, along with the role of gut microbiota in this effect, both remain unclear. Here, we determined the quercetin's effect on attenuating diarrhea, intestinal damage, and redox imbalance, as well as the role of gut microbiota by transferring the quercetin-treated fecal microbiota to the recipient piglets. The results showed that dietary quercetin supplementation decreased piglets' fecal scores improved intestinal damage by increasing tight junction protein occludin, villus height, and villus height/crypt depth ratio but decreased crypt depth and intestinal epithelial apoptosis (TUNEL staining). Quercetin also increased antioxidant capacity indices, including total antioxidant capacity, catalase, and glutathione/oxidized glutathione disulfide but decreased oxidative metabolite malondialdehyde in the jejunum tissue. Fecal microbiota transplantation (FMT) from quercetin-treated piglets had comparable effects on improving intestinal damage and antioxidative capacity than dietary quercetin supplementation. Further analysis of gut microbiota using 16S rDNA sequencing showed that dietary quercetin supplementation or FMT shifted the structure and increased the diversity of gut microbiota. Especially, anaerobic trait and carbohydrate metabolism functions of gut microbiota were enriched after dietary quercetin supplementation and FMT, which may owe to the increased antioxidative capacity of intestine. Quercetin increased the relative abundances of Fibrobacteres, Akkermansia muciniphila, Clostridium butyricum, Clostridium celatum, and Prevotella copri but decreased the relative abundances of Proteobacteria, Lactobacillus coleohominis, and Ruminococcus bromii. Besides, quercetin-shifted bacteria and carbohydrate metabolites short chain fatty acids were significantly related to the indices of antioxidant capacity and intestinal integrity. Overall, dietary quercetin supplementation attenuated diarrhea and intestinal damage by enhancing the antioxidant capacity and regulating gut microbial structure and metabolism in piglets.}, }
@article {pmid34949194, year = {2021}, author = {Wu, Y and Zhang, Y and Xie, B and Abdelgawad, A and Chen, X and Han, M and Shang, Y and Yuan, S and Zhang, J}, title = {RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.}, journal = {Journal of neuroinflammation}, volume = {18}, number = {1}, pages = {300}, pmid = {34949194}, issn = {1742-2094}, support = {82071480//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Atrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is to assess the effect of ANP on bacterial lipopolysaccharide (LPS)-induced endotoxemia-derived neuroinflammation and cognitive impairment.
METHODS: LPS (5 mg/kg) was given intraperitoneally to mice. Recombinant human ANP (rhANP) (1.0 mg/kg) was injected intravenously 24 h before and/or 10 min after LPS injection. Subdiaphragmatic vagotomy (SDV) was performed 14 days before LPS injection or 28 days before fecal microbiota transplantation (FMT). ANA-12 (0.5 mg/kg) was administrated intraperitoneally 30 min prior to rhANP treatment.
RESULTS: LPS (5.0 mg/kg) induced remarkable splenomegaly and an increase in the plasma cytokines at 24 h after LPS injection. There were positive correlations between spleen weight and plasma cytokines levels. LPS also led to increased protein levels of ionized calcium-binding adaptor molecule (iba)-1, cytokines and inducible nitric oxide synthase (iNOS) in the hippocampus. LPS impaired the natural and learned behavior, as demonstrated by an increase in the latency to eat the food in the buried food test and a decrease in the number of entries and duration in the novel arm in the Y maze test. Combined prophylactic and therapeutic treatment with rhANP reversed LPS-induced splenomegaly, hippocampal and peripheral inflammation as well as cognitive impairment. However, rhANP could not further enhance the protective effects of SDV on hippocampal and peripheral inflammation. We further found that PGF mice transplanted with fecal bacteria from rhANP-treated endotoxemia mice alleviated the decreased protein levels of hippocampal polyclonal phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotrophic factor (BDNF) and cognitive impairment, which was abolished by SDV. Moreover, TrkB/BDNF signaling inhibitor ANA-12 abolished the improving effects of rhANP on LPS-induced cognitive impairment.
CONCLUSIONS: Our results suggest that rhANP could mitigate LPS-induced hippocampal inflammation and cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.}, }
@article {pmid34946163, year = {2021}, author = {Kosaka, S and Nadatani, Y and Higashimori, A and Otani, K and Fujimoto, K and Nagata, Y and Ominami, M and Fukunaga, S and Hosomi, S and Kamata, N and Tanaka, F and Nagami, Y and Taira, K and Imoto, S and Uematsu, S and Watanabe, T and Fujiwara, Y}, title = {Ovariectomy-Induced Dysbiosis May Have a Minor Effect on Bone in Mice.}, journal = {Microorganisms}, volume = {9}, number = {12}, pages = {}, doi = {10.3390/microorganisms9122563}, pmid = {34946163}, issn = {2076-2607}, support = {17K15962//JSPS KAKENHI/ ; }, abstract = {We determined the bone mineral density (BMD) and the expression of serum bone formation marker (procollagen type I N-terminal propeptide: PINP) and bone resorption marker (C-terminal telopeptide of collagen: CTX) by ELISA to evaluate ovariectomy-induced osteoporosis in ovariectomized (OVX) mice. The intestinal microbiota of the mice was assessed using 16S rRNA gene sequencing. OVX mice exhibited a lower BMD of 87% with higher serum levels of CTX and PINP compared to sham-operated (sham) mice. The cecum microbiome of OVX mice showed lower bacterial diversity than that of sham mice. TNFα mRNA levels in the colon were 1.6 times higher, and zonula occludens-1 mRNA and protein expression were lower in OVX mice than in sham mice, suggesting that ovariectomy induced inflammation and increased intestinal permeability. Next, we used antibiotic treatment followed by fecal microbiota transplantation (FMT) to remodel the gut microbiota in the OVX mice. A decrease in PINP was observed in antibiotic-treated mice, while there was no change in BMD or CTX between mice with and without antibiotic treatment. Oral transplantation of the luminal cecal content of OVX or sham mice to antibiotic-treated mice did not affect the BMD or PINP and CTX expression. Additionally, transplantation of the luminal contents of OVX or sham mice to antibiotic-treated OVX mice had similar effects on BMD, PINP, and CTX. In conclusion, although ovariectomy induces dysbiosis in the colon, the changes in the gut microbiota may only have a minor role in ovariectomy-induced osteoporosis.}, }
@article {pmid34946139, year = {2021}, author = {Broecker, F and Moelling, K}, title = {The Roles of the Virome in Cancer.}, journal = {Microorganisms}, volume = {9}, number = {12}, pages = {}, doi = {10.3390/microorganisms9122538}, pmid = {34946139}, issn = {2076-2607}, abstract = {Viral infections as well as changes in the composition of the intestinal microbiota and virome have been linked to cancer. Moreover, the success of cancer immunotherapy with checkpoint inhibitors has been correlated with the intestinal microbial composition of patients. The transfer of feces-which contain mainly bacteria and their viruses (phages)-from immunotherapy responders to non-responders, known as fecal microbiota transplantation (FMT), has been shown to be able to convert some non-responders to responders. Since phages may also increase the response to immunotherapy, for example by inducing T cells cross-reacting with cancer antigens, modulating phage populations may provide a new avenue to improve immunotherapy responsiveness. In this review, we summarize the current knowledge on the human virome and its links to cancer, and discuss the potential utility of bacteriophages in increasing the responder rate for cancer immunotherapy.}, }
@article {pmid34945118, year = {2021}, author = {Popa, D and Neamtu, B and Mihalache, M and Boicean, A and Banciu, A and Banciu, DD and Moga, DFC and Birlutiu, V}, title = {Fecal Microbiota Transplant in Severe and Non-Severe Clostridioides difficile Infection. Is There a Role of FMT in Primary Severe CDI?.}, journal = {Journal of clinical medicine}, volume = {10}, number = {24}, pages = {}, doi = {10.3390/jcm10245822}, pmid = {34945118}, issn = {2077-0383}, support = {LBUS-IRG-2021-07//Lucian Blaga University of Sibiu & Hasso Plattner Foundation/ ; }, abstract = {BACKGROUND: Faecal microbiota transplant (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) with cure rates ranging between 85 and 92%. The FMT role for primary Clostridioides difficile infection (CDI) has yet to be settled because of limited data and small-sample studies presented in the current literature. Our study goals were to report the risk factors and the risk of recurrence after FMT for each CDI episode (first, second, and third) and to explore if there is a role of FMT in primary severe CDI.
METHODS: We conducted a retrospective study to analyze the clinical characteristics and the outcomes of 96 FMT patients with a prior 10 day course of antibiotic treatment in the medical records, of which 71 patients with recurrent CDI and 25 patients with a primary CDI.
RESULTS: The overall primary cure rate in our study was 88.5% and the primary cure rate for the severe forms was 85.7%. The data analysis revealed 5.25%, 15.15%, and 27.3% FMT recurrence rates for primary, secondary, and tertiary severe CDI. The risk of recurrence was significantly associated with FMT after the second and the third CDI severe episodes (p < 0.05), but not with FMT after the first severe CDI episode.
CONCLUSIONS: This study brings new data in supporting the FMT role in CDI treatment, including the primary severe CDI, however, further prospective and controlled studies on larger cohorts should be performed in this respect.}, }
@article {pmid34764444, year = {2021}, author = {Rolling, T and Zhai, B and Gjonbalaj, M and Tosini, N and Yasuma-Mitobe, K and Fontana, E and Amoretti, LA and Wright, RJ and Ponce, DM and Perales, MA and Xavier, JB and van den Brink, MRM and Markey, KA and Peled, JU and Taur, Y and Hohl, TM}, title = {Haematopoietic cell transplantation outcomes are linked to intestinal mycobiota dynamics and an expansion of Candida parapsilosis complex species.}, journal = {Nature microbiology}, volume = {6}, number = {12}, pages = {1505-1515}, pmid = {34764444}, issn = {2058-5276}, support = {U01 AI124275/AI/NIAID NIH HHS/United States ; R01 AI093808/AI/NIAID NIH HHS/United States ; R21 AI156157/AI/NIAID NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/isolation & purification ; Biodiversity ; Candida parapsilosis/genetics/*growth & development/physiology ; Dysbiosis/immunology/microbiology ; Feces/microbiology ; Fungi/classification/genetics/isolation & purification ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Humans ; Intestines/immunology/microbiology ; Prospective Studies ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {Allogeneic haematopoietic cell transplantation (allo-HCT) induces profound shifts in the intestinal bacterial microbiota. The dynamics of intestinal fungi and their impact on clinical outcomes during allo-HCT are not fully understood. Here we combined parallel high-throughput fungal ITS1 amplicon sequencing, bacterial 16S amplicon sequencing and fungal cultures of 1,279 faecal samples from a cohort of 156 patients undergoing allo-HCT to reveal potential trans-kingdom dynamics and their association with patient outcomes. We saw that the overall density and the biodiversity of intestinal fungi were stable during allo-HCT but the species composition changed drastically from day to day. We identified a subset of patients with fungal dysbiosis defined by culture positivity (n = 53) and stable expansion of Candida parapsilosis complex species (n = 19). They presented with distinct trans-kingdom microbiota profiles, characterized by a decreased intestinal bacterial biomass. These patients had worse overall survival and higher transplant-related mortality independent of candidaemia. This expands our understanding of the clinical significance of the mycobiota and suggests that targeting fungal dysbiosis may help to improve long-term patient survival.}, }
@article {pmid33493658, year = {2021}, author = {Fang, Y and Zhang, J and Zhu, S and He, M and Ma, S and Jia, Q and Sun, Q and Song, L and Wang, Y and Duan, L}, title = {Berberine ameliorates ovariectomy-induced anxiety-like behaviors by enrichment in equol generating gut microbiota.}, journal = {Pharmacological research}, volume = {165}, number = {}, pages = {105439}, doi = {10.1016/j.phrs.2021.105439}, pmid = {33493658}, issn = {1096-1186}, mesh = {Animals ; Anxiety/*drug therapy/etiology/*metabolism ; Berberine/pharmacology/*therapeutic use ; Equol/*metabolism ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Ovariectomy/*adverse effects ; Rats ; Rats, Sprague-Dawley ; }, abstract = {The gut microbiota is recognized as a promising therapeutic target for anxiety. Berberine (BBR) has shown efficacy in the treatment of diseases such as postmenopausal osteoporosis, obesity, and type 2 diabetes through regulating the gut microbiota. However, the effects of BBR on postmenopausal anxiety are still unclear. The purpose of the study is to test whether BBR ameliorates anxiety by modulating intestinal microbiota under estrogen-deficient conditions. Experimental anxiety was established in specific pathogen-free (SPF) ovariectomized (OVX) rats, which were then treated with BBR for 4 weeks before undergoing behavioral tests. Open field and elevated plus maze tests demonstrated that BBR treatment significantly ameliorated anxiety-like behaviors of OVX rats compared with vehicle-treated counterparts. Moreover, as demonstrated by 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC/MS) analysis, BBR-treated OVX rats harbored a higher abundance of beneficial gut microbes, such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia, and exhibited increased equol generation. Notably, gavage feeding of BBR had no significant anti-anxiety effects on germ-free (GF) rats that underwent ovariectomy, whereas GF rats transplanted with fecal microbiota from SPF rats substantially phenocopied the donor rats in terms of anxiety-like symptoms and isoflavone levels. This study indicates that the gut microbiota is critical in the treatment of ovariectomy-aggravated anxiety, and that BBR modulation of the gut microbiota is a promising therapeutic strategy for treating postmenopausal symptoms of anxiety.}, }
@article {pmid34938813, year = {2021}, author = {Wang, S and Chen, H and Wen, X and Mu, J and Sun, M and Song, X and Liu, B and Chen, J and Fan, X}, title = {The Efficacy of Fecal Microbiota Transplantation in Experimental Autoimmune Encephalomyelitis: Transcriptome and Gut Microbiota Profiling.}, journal = {Journal of immunology research}, volume = {2021}, number = {}, pages = {4400428}, doi = {10.1155/2021/4400428}, pmid = {34938813}, issn = {2314-7156}, abstract = {Objective: To study the protective effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and reveal its potential intestinal microflora-dependent mechanism through analyses of the intestinal microbiota and spinal cord transcriptome in mice.
Method: We measured the severity of disease by clinical EAE scores and H&E staining. Gut microbiota alteration in the gut and differentially expressed genes (DEGs) in the spinal cord were analyzed through 16S rRNA and transcriptome sequencing. Finally, we analyzed associations between the relative abundance of intestinal microbiota constituents and DEGs.
Results: We observed that clinical EAE scores were lower in the EAE+FMT group than in the EAE group. Meanwhile, mice in the EAE+FMT group also had a lower number of infiltrating cells. The results of 16S rRNA sequence analysis showed that FMT increased the relative abundance of Firmicutes and Proteobacteria and reduced the abundance of Bacteroides and Actinobacteria. Meanwhile, FMT could modulate gut microbiota balance, especially via increasing the relative abundance of g_Adlercreutzia, g_Sutterella, g_Prevotella_9, and g_Tyzzerella_3 and decreasing the relative abundance of g_Turicibacter. Next, we analyzed the transcriptome of mouse spinal cord tissue and found that 1476 genes were differentially expressed between the EAE and FMT groups. The analysis of these genes showed that FMT mainly participated in the inflammatory response. Correlation analysis between gut microbes and transcriptome revealed that the relative abundance of Adlercreutzia was correlated with the expression of inflammation-related genes negatively, including Casp6, IL1RL2 (IL-36R), IL-17RA, TNF, CCL3, CCR5, and CCL8, and correlated with the expression of neuroprotection-related genes positively, including Snap25, Edil3, Nrn1, Cpeb3, and Gpr37.
Conclusion: Altogether, FMT may selectively regulate gene expression to improve inflammation and maintain the stability of the intestinal environment in a gut microbiota-dependent manner.}, }
@article {pmid34933877, year = {2021}, author = {Hofmeister, M and Clement, F and Patten, S and Li, J and Dowsett, LE and Farkas, B and Mastikhina, L and Egunsola, O and Diaz, R and Cooke, NCA and Taylor, VH}, title = {The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis.}, journal = {CMAJ open}, volume = {9}, number = {4}, pages = {E1195-E1204}, doi = {10.9778/cmajo.20200283}, pmid = {34933877}, issn = {2291-0026}, abstract = {BACKGROUND: Despite their popularity, the efficacy of interventions targeting gut microbiota to improve depressive symptoms is unknown. Our objective is to summarize the effect of microbiome-targeting interventions on depressive symptoms.
METHODS: We conducted a systematic review and meta-analysis. We searched MEDLINE, Embase, PsycINFO, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews and the Cochrane Controlled Register of Trials from inception to Mar. 5, 2021. We included studies that evaluated probiotic, prebiotic, synbiotic, paraprobiotic or fecal microbiota transplant interventions in an adult population (age ≥ 18 yr) with an inactive or placebo comparator (defined by the absence of active intervention). Studies must have measured depressive symptoms with a validated scale, and used a randomized controlled trial study design. We conducted a random effects meta-analysis of change scores, using standardized mean difference as the measure of effect.
RESULTS: Sixty-two studies formed the final data set, with 50 included in the meta-analysis. Probiotic, prebiotic, and synbiotic interventions on depressive symptoms showed statistically significant benefits. In the single studies evaluating each of fecal microbiota transplant and paraprobiotic interventions, neither showed a statistically significant benefit.
INTERPRETATION: Despite promising findings of benefit of probiotic, prebiotic and synbiotic interventions for depressive symptoms in study populations, there is not yet strong enough evidence to favour inclusion of these interventions in treatment guidelines for depression. Critical questions about species administered, dosage and timing relative to other antidepressant medications remain to be answered.
STUDY REGISTRATION: PROSPERO no. 143178.}, }
@article {pmid34588655, year = {2021}, author = {Hofer, U}, title = {Faecal phage transplant to the rescue?.}, journal = {Nature reviews. Microbiology}, volume = {19}, number = {12}, pages = {744}, pmid = {34588655}, issn = {1740-1534}, mesh = {*Bacteriophages/genetics ; Fecal Microbiota Transplantation ; Feces ; }, }
@article {pmid33633259, year = {2021}, author = {Sasaki, K and Sasaki, D and Sasaki, K and Nishidono, Y and Yamamori, A and Tanaka, K and Kondo, A}, title = {Growth stimulation of Bifidobacterium from human colon using daikenchuto in an in vitro model of human intestinal microbiota.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4580}, pmid = {33633259}, issn = {2045-2322}, mesh = {Bifidobacterium/*drug effects/growth & development/isolation & purification ; Colon/*microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Humans ; In Vitro Techniques ; Panax ; Plant Extracts/*pharmacology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA/methods ; Zanthoxylum ; Zingiberaceae ; }, abstract = {Daikenchuto (DKT) is a Japanese traditional herbal (Kampo) medicine containing ginseng, processed ginger, and Japanese or Chinese pepper. We aimed to determine how DKT affects human colonic microbiota. An in vitro microbiota model was established using fecal inocula collected from nine healthy volunteers, and each model was found to retain operational taxonomic units similar to the ones in the original human fecal samples. DKT was added to the in vitro microbiota model culture at a concentration of 0.5% by weight. Next-generation sequencing of bacterial 16S rRNA gene revealed a significant increase in the relative abundance of bacteria related to the Bifidobacterium genus in the model after incubation with DKT. In pure cultures, DKT significantly promoted the growth of Bifidobacterium adolescentis, but not that of Fusobacterium nucleatum or Escherichia coli. Additionally, in pure cultures, B. adolescentis transformed ginsenoside Rc to Rd, which was then probably utilized for its growth. Our study reveals the in vitro bifidogenic effect of DKT that likely contributes to its beneficial effects on the human colon.}, }
@article {pmid34931881, year = {2021}, author = {Chen, X and Wu, Q and Gao, X and Wang, H and Zhu, J and Xia, G and He, Y and Song, W and Xu, K}, title = {Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic Stroke.}, journal = {mSystems}, volume = {6}, number = {6}, pages = {e0130421}, doi = {10.1128/msystems.01304-21}, pmid = {34931881}, issn = {2379-5077}, support = {201904010091//Science and Technology Program of Guangzhou/ ; 2018M630967//China Postdoctoral Science Foundation/ ; NSFC31800415//National Natural Science Foundation of China (NSFC)/ ; NSFC82022044//National Natural Science Foundation of China (NSFC)/ ; }, abstract = {Type 2 diabetes (T2D) is an independent risk factor for acute ischemic stroke (AIS), but the underlying mechanisms remain elusive. Because the gut microbiota plays a causal role in both T2D and AIS, we wondered whether gut dysbiosis in T2D aggravates stroke progression. We recruited 35 T2D, 90 AIS, 60 AIS with T2D (AIS_T2D) patients, and 55 healthy controls and found that AIS and T2D had an additive effect on AIS_T2D patient gut dysbiosis by exhibiting the largest difference from the heathy controls. In addition, we found that the degree of gut dysbiosis associated with T2D was positively correlated with the National Institutes of Health Stroke Scale (NIHSS), modified Rankin score (mRS), and Essen stroke risk score in patients with AIS, including AIS and AIS_T2D patients. Compared with mice colonized with gut microbiota from healthy controls poststroke modeling, germfree (GF) mice colonized with gut microbiota from T2D patients showed exacerbated cerebral injury and impaired gut barrier function. Specifically, exacerbated brain injury and gut barrier dysfunction in T2D-treated GF mice were significantly associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. Our study showed that T2D and AIS have an additive effect on AIS_T2D patient gut microbiota dysbiosis. T2D-associated gut microbiota dysbiosis is associated with stroke severity in AIS patients and aggravates stroke progression in mice. IMPORTANCE We demonstrated an additive effect of type 2 diabetes (T2D) and acute ischemic stroke (AIS) on AIS with T2D (AIS_T2D) patient gut microbiota dysbiosis, and gut dysbiosis associated with T2D was positively correlated with stroke severity in AIS patients. Through animal experiments, we found that cerebral injury was exacerbated by fecal microbiota transplantation from T2D patients compared with that from healthy controls, which was associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. This study provided a novel view that links T2D and AIS through gut microbial dysbiosis.}, }
@article {pmid34931478, year = {2021}, author = {Mashiah, J and Karady, T and Fliss-Isakov, N and Sprecher, E and Slodownik, D and Artzi, O and Samuelov, L and Ellenbogen, E and Godneva, A and Segal, E and Maharshak, N}, title = {Clinical efficacy of fecal microbial transplantation treatment in adults with moderate-to-severe atopic dermatitis.}, journal = {Immunity, inflammation and disease}, volume = {}, number = {}, pages = {}, doi = {10.1002/iid3.570}, pmid = {34931478}, issn = {2050-4527}, abstract = {BACKGROUND: Atopic dermatitis (AD) is a remitting relapsing chronic eczematous pruritic disease. Several studies suggest that gut microbiota may influence AD by immune system regulation.
METHODS: We performed the first in-human efficacy and safety assessment of fecal microbiota transplantation (FMT) for AD adult patients. All patients received 2 placebo transplantations followed by 4 FMTs each 2 weeks apart. AD severity and fecal microbiome profile were evaluated by the Scoring Atopic Dermatitis Score (SCORAD), the weekly frequency of topical corticosteroids usage, and gut microbiota metagenomic analysis, at the study beginning, before every FMT, and 1-8 months after the last FMT.
RESULTS: Nine patients completed the study protocol. There was no significant change in the SCORAD score following the two placebo transplants. The average SCORAD score significantly decreased from baseline at Weeks 4-12 (before and 2 weeks after 4 times of FMT) (59.2 ± 34.9%, Wilcoxon p = .011), 50% and 75% decrease was achieved by 7 (77%) and 4 (44%) patients, respectively. At Week 18 (8 weeks after the last FMT) the average SCORAD score decreased from baseline at Week 4 (85.5 ± 8.4%, Wilcoxon p = .018), 50% and 75% decrease was achieved by 7 (77%) and 6 (66.7%) patients respectively. Weekly topical corticosteroids usage was diminished during the study and follow-up period as well. Two patients had a quick relapse and were switched to a different treatment. Two patients developed exacerbations alleviated after an additional fifth FMT. Metagenomic analysis of the fecal microbiota of patients and donors showed bacterial strains transmission from donors to patients. No adverse events were recorded during the study and follow-up period.
CONCLUSIONS: FMT may be a safe and effective therapeutic intervention for AD patients, associated with transfer of specific microbial species from the donors to the patients. Further studies are required to reconfirm these results.}, }
@article {pmid34926663, year = {2021}, author = {Zhang, Y and Xue, X and Su, S and Zhou, H and Jin, Y and Shi, Y and Lin, J and Wang, J and Li, X and Yang, G and Philpott, JR and Liang, J}, title = {Patients and physicians' attitudes change on fecal microbiota transplantation for inflammatory bowel disease over the past 3 years.}, journal = {Annals of translational medicine}, volume = {9}, number = {21}, pages = {1619}, doi = {10.21037/atm-21-3683}, pmid = {34926663}, issn = {2305-5839}, abstract = {Background: In the past 3 years, increasing data and experience has become available regarding fecal microbiota transplantation (FMT) for the treatment of inflammatory bowel disease (IBD). However, how this increase in knowledge has impacted the attitudes of patients and physicians is largely unknown. This study aimed to investigate the change of patients' and physicians' attitudes towards FMT for IBD treatment.
Methods: Questionnaires for patient and physician attitude on FMT for IBD were pilot-tested and developed. Patients and physicians from the same groups completed the questionnaires in 2016 and 2019, separately. The attitudes towards efficacy, adverse events, and methodological features of FMT in 2016 were compared with those in 2019.
Results: A total of 1,255 questionnaires from 486 patients and 769 physicians were collected. Over the 3 years, an increased number of patients had heard of FMT and had similarly positive opinions towards using FMT for IBD therapy. Additionally, patients retained the tendency to overestimate the efficacy. The physicians' perceptions became closer to the findings reported in recent studies in 2019 compared with 2016. However, only a minority of patients and physicians understood the frequency required of FMT courses for induction of clinical remission. In particular, both patients and physicians underestimated the risk of mild adverse events and IBD flare.
Conclusions: Patients are receptive towards FMT as therapy for IBD but opportunity remains to improve understanding of benefit and potential risks. Physicians also demonstrated knowledge gaps in use of this therapy. Aligning patient preference and physician knowledge gap will lead to better education and facilitate the development of decision-making guidelines.}, }
@article {pmid34925385, year = {2021}, author = {Pan, Q and Guo, F and Huang, Y and Li, A and Chen, S and Chen, J and Liu, HF and Pan, Q}, title = {Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus: Novel Insights into Mechanisms and Promising Therapeutic Strategies.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {799788}, doi = {10.3389/fimmu.2021.799788}, pmid = {34925385}, issn = {1664-3224}, abstract = {Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that was traditionally thought to be closely related to genetic and environmental risk factors. Although treatment options for SLE with hormones, immunosuppressants, and biologic drugs are now available, the rates of clinical response and functional remission of these drugs are still not satisfactory. Currently, emerging evidence suggests that gut microbiota dysbiosis may play crucial roles in the occurrence and development of SLE, and manipulation of targeting the gut microbiota holds great promises for the successful treatment of SLE. The possible mechanisms of gut microbiota dysbiosis in SLE have not yet been well identified to date, although they may include molecular mimicry, impaired intestinal barrier function and leaky gut, bacterial biofilms, intestinal specific pathogen infection, gender bias, intestinal epithelial cells autophagy, and extracellular vesicles and microRNAs. Potential therapies for modulating gut microbiota in SLE include oral antibiotic therapy, fecal microbiota transplantation, glucocorticoid therapy, regulation of intestinal epithelial cells autophagy, extracellular vesicle-derived miRNA therapy, mesenchymal stem cell therapy, and vaccination. This review summarizes novel insights into the mechanisms of microbiota dysbiosis in SLE and promising therapeutic strategies, which may help improve our understanding of the pathogenesis of SLE and provide novel therapies for SLE.}, }
@article {pmid34923901, year = {2021}, author = {Guo, Q and Lin, H and Chen, P and Tan, S and Wen, Z and Lin, L and He, J and Wen, J and Lu, S}, title = {Dynamic changes of intestinal flora in patients with irritable bowel syndrome combined with anxiety and depression after oral administration of enterobacteria capsules.}, journal = {Bioengineered}, volume = {}, number = {}, pages = {}, doi = {10.1080/21655979.2021.1999374}, pmid = {34923901}, issn = {2165-5987}, abstract = {This study investigated the clinical characteristics and dynamic changes of intestinal bacterial community to evaluate the curative effect of fecal microbiota transplantation (FMT) on irritable bowel syndrome with predominant diarrhea (IBS-D) comorbid with anxiety and depression. Total two treatments were designed in randomize-controlled trial includes oral FMT capsules with 1 week (A1), 8 weeks (A2), and 12 weeks (A3), as well as oral empty capsules with 1 week (B1), 8 weeks (B2), and 12 weeks (B3) as control for comparation. The positive therapeutic effects occurred in FMT colonized patient with IBS-D comorbid psychological disorder, demonstrated at alleviated IBS-D severity (IBS-SSS score from 291.11 reduced to 144.44), altered stool type (from 6 changed to 4), reduced anxiety and depression scores (from 18.33 to 8.39 and from 22.33 to 17.78) after FMT treated 12 weeks. The FMT therapy improved bacterial alpha diversity and the majority bacterial community predominant by Bacteroidetes and Firmicutes, and the relative abundance (RA) was higher after FMT treated 12 weeks (50.61% and 45.52%) than control (47.62% and 38.96%). In short, FMT therapy has great potential for IBS-D patients combined with anxiety and depression by alleviated clinical symptoms and restore the intestinal micro-ecology.[Figure: see text].}, }
@article {pmid34922582, year = {2021}, author = {He, Y and Du, W and Xiao, S and Zeng, B and She, X and Liu, D and Du, H and Li, L and Li, F and Ai, Q and He, J and Song, C and Wei, H and Zhao, X and Yu, J}, title = {Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {510}, pmid = {34922582}, issn = {1479-5876}, support = {82001602//National Natural Science Foundation of China/ ; 81971431//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Necrotizing enterocolitis (NEC) remains a life-threatening disease in neonates. Numerous studies have shown a correlation between the intestinal microbiota and NEC, but the causal link remains unclear. This study aimed to demonstrate the causal role of gut microbiota in NEC and explore potential mechanisms involved.
METHODS: Eighty-one fecal samples from patients with NEC and eighty-one matched controls (matched to the NEC infants by gestational age, birth weight, date of birth, mode of delivery and feeding patterns) were collected. To explore if altered gut microbiota contributes to the pathogenesis of NEC, fecal microbiota transplantation (FMT) was carried out in germ-free (GF) mice prior to a NEC-induction protocol that included exposure to hypoxia and cold stress. Butyric acid was also administered to demonstrate its role in NEC. The fecal microbiota from patients and mice were analyzed by 16S rRNA gene sequencing analysis. Short chain fatty acid (SCFA) levels were measured by gas chromatography-mass spectrometry (GC-MS). The ontogeny of T cells and regulatory T cells (Tregs) in lamina propria mononuclear cells (LPMC) from the ileum of patients and mice were isolated and analyzed by flow cytometry.The transcription of inflammatory cytokines was quantified by qRT-PCR.
RESULTS: NEC patients had increased Proteobacteria and decreased Firmicutes and Bacteroidetes compared to fecal control samples, and the level of butyric acid in the NEC group was lower than the control group. FMT in GF mice with samples from NEC patients achieved a higher histological injury scores when compared to mice that received FMT with control samples. Alterations in microbiota and butyrate levels were maintained in mice following FMT. The ratio of Treg/CD4+T (Thelper) cells was reduced in both NEC patients and mice modeling NEC following FMT.
CONCLUSIONS: The microbiota was found to have NEC and the microbial butyrate-Treg axis was identified as a potential mechanism for the observed effects.}, }
@article {pmid34920070, year = {2021}, author = {Zhang, L and Wang, Y and Wu, F and Wang, X and Feng, Y and Wang, Y}, title = {MDG, an Ophiopogon japonicus polysaccharide, inhibits non-alcoholic fatty liver disease by regulating the abundance of Akkermansia muciniphila.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ijbiomac.2021.12.036}, pmid = {34920070}, issn = {1879-0003}, abstract = {MDG, a polysaccharide derived from Ophiopogon japonicus, displays a protective effect against obesity and non-alcoholic fatty liver disease (NAFLD). However, there is no definitive evidence proving the specific mechanism of MDG against NAFLD. The results showed MDG supplementation ameliorated lipid accumulation, liver steatosis, and chronic inflammation in high-fat diet-induced NAFLD mice. Besides, MDG increased the abundance and diversity of microbial communities in the gut. These effects were mediated by the colonization of fecal microbiota. Further investigation revealed that Akkermansia muciniphila levels correlated negatively with NAFLD development, and lipid metabolism-related signaling might be the key regulator. Our study suggested that MDG treatment could inhibit obesity and the NAFLD process by modulating lipid-related pathways via altering the structure and diversity of gut microbiota. In addition, Akkermansia miniciphila might be a promising candidate in future research into NAFLD.}, }
@article {pmid34918995, year = {2021}, author = {Qi, L and Huang, X and He, C and Ji, D and Li, F}, title = {Steroid-resistant intestinal aGVHD and refractory CMV and EBV infections complicated by haplo-HSCT were successfully rescued by FMT and CTL infusion.}, journal = {The Journal of international medical research}, volume = {49}, number = {12}, pages = {3000605211063292}, doi = {10.1177/03000605211063292}, pmid = {34918995}, issn = {1473-2300}, abstract = {Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) produces similar survival outcomes as HLA-matched sibling donor allogeneic HCST in younger patients with acquired severe aplastic anemia (SAA). This study reported a 29-years-old man with SAA and intracranial hemorrhage who underwent haplo-HSCT with a modified BU/CY + ATG conditioning regimen. Neutrophil and platelet engraftment were both achieved on day 14 after HSCT. The patient developed grade IV acute graft-versus-host disease (aGVHD) on day 20 and acquired cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections on day 47. After the failure of methylprednisolone, basiliximab, ruxolitinib, and antiviral treatment, the patient was diagnosed with steroid-resistant grade IV aGVHD and refractory CMV and EBV infections. We performed fecal microbiota transplantation and infused CMV- and EBV-specific cytotoxic T lymphocytes. After that the stool volume and frequency gradually decreased, and viral DNA was undetectable on day 80. This report provides helpful clinical experience for treating steroid-resistant aGVHD and refractory viral infections.}, }
@article {pmid34918486, year = {2021}, author = {Wang, Y and Xie, Z}, title = {Exploring the role of gut microbiome in male reproduction.}, journal = {Andrology}, volume = {}, number = {}, pages = {}, doi = {10.1111/andr.13143}, pmid = {34918486}, issn = {2047-2927}, abstract = {BACKGROUND: The impact of the gut microbiome on the organism has become a growing research focus with the development of 16S rRNA sequencing. However, the effect of the gut microbiome in male reproduction has yet to be investigated.
OBJECTIVE: To overview on possible mechanisms by which gut microbiome could affect male reproduction and therapeutic opportunities related to the gut microbiome METHODS: Authors searched PubMed/MEDLINE, EMBASE, Web of Science, Cochrane Library for medical subject headings terms and free text words referred to "male infertility" "testis" "gut microbiome" "insulin resistance" "erectile dysfunction" "therapy" "sex hormones" "Genital Diseases." until Dec 2nd 2021.
RESULTS: Evidence suggests that immune system activation caused by the gut microbiome translocation not only leads to testicular and epididymal inflammation but can also induce insulin resistance together with gastrointestinal hormones such as leptin and ghrelin, which in turn affects the secretion of various sex hormones such as LH, FSH, and T to regulate spermatogenesis. In addition, the gut microbiome can influence spermatogenesis by controlling and metabolizing androgens as well as affecting the blood-testis barrier. It also promotes vascular inflammation by raising trimethylamine-N-oxide (TMAO) levels in the blood, which causes erectile dysfunction. Testicular microbiome and gut microbiome can interact to influence male reproductive function. This study discusses therapeutic options such as probiotics, prebiotics, and fecal microbiota transplantation, as well as the challenges and opportunities behind ongoing research, and emphasizes the need for additional research in the future to demonstrate the links and underlying mechanisms between gut microbiome and male reproduction. Therapeutic options such as probiotic, prebiotics and fecal microbiota transplantation are potential treatments for male infertility.
DISCUSSION AND CONCLUSION: Gut microbiota may have a causal role in male reproduction health, therapeutic strategies such as supplementation with appropriate probiotics could be undertaken as a complementary treatment. In the future, additional research is needed to demonstrate the links and underlying mechanisms between gut microbiome and male reproduction. This article is protected by copyright. All rights reserved.}, }
@article {pmid34531862, year = {2021}, author = {Islam, SMS and Ryu, HM and Sayeed, HM and Byun, HO and Jung, JY and Kim, HA and Suh, CH and Sohn, S}, title = {Eubacterium rectale Attenuates HSV-1 Induced Systemic Inflammation in Mice by Inhibiting CD83.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {712312}, pmid = {34531862}, issn = {1664-3224}, mesh = {Administration, Oral ; Adult ; Animals ; Antigens, CD/biosynthesis/genetics ; Bacteria/classification/isolation & purification ; Behcet Syndrome/drug therapy/microbiology/*therapy ; Butyrates/metabolism/therapeutic use ; Colchicine/therapeutic use ; Combined Modality Therapy ; Dendritic Cells/immunology ; Disease Models, Animal ; Down-Regulation/drug effects ; *Eubacterium ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Herpes Simplex/immunology/microbiology/therapy ; Herpesvirus 1, Human/*pathogenicity ; Humans ; Immunoglobulins/biosynthesis/genetics ; Inflammation/drug therapy/*therapy ; Interleukin-17/blood ; Killer Cells, Natural/immunology ; Male ; Membrane Glycoproteins/*antagonists & inhibitors/biosynthesis/genetics ; Metagenome ; Mice ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Random Allocation ; Ribotyping ; Severity of Illness Index ; }, abstract = {The purpose of this study was to determine whether administration of the microorganism Eubacterium rectale (E. rectale) could regulate dendritic cell (DC) activation and systemic inflammation in herpes simplex virus type 1-induced Behçet's disease (BD). E. rectale, butyrate-producing bacteria, was administered to BD mice. Peripheral blood leukocytes (PBL) and lymph node cells were isolated and analyzed by flow cytometry. 16S rRNA metagenomic analysis was performed in the feces of mice to determine the differences in the composition of the microbial population between normal and BD mice. Serum cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of DC activation marker CD83 positive cells was significantly increased in PBL of BD mice. Frequencies of CD83+ cells were also significantly increased in patients with active BD. 16S rRNA metagenomic analysis revealed different gut microbiota composition between normal and BD mice. The administration of E. rectale to BD mice reduced the frequency of CD83+ cells and significantly increased the frequency of NK1.1+ cells with the improvement of symptoms. The co-administration of colchicine and E. rectale also significantly reduced the frequency of CD83+ cells. Differences in gut microbiota were observed between normal mice and BD mice, and the administration of E. rectale downregulated the frequency of CD83, which was associated with BD deterioration. These data indicate that E. rectale could be a new therapeutic adjuvant for BD management.}, }
@article {pmid34512631, year = {2021}, author = {Bozward, AG and Ronca, V and Osei-Bordom, D and Oo, YH}, title = {Gut-Liver Immune Traffic: Deciphering Immune-Pathogenesis to Underpin Translational Therapy.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {711217}, pmid = {34512631}, issn = {1664-3224}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Antibodies, Monoclonal, Humanized/therapeutic use ; Bile Acids and Salts/physiology ; Cholangitis, Sclerosing/drug therapy/*etiology/immunology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Inflammatory Bowel Diseases/etiology ; Intestinal Mucosa/*immunology ; Liver/*immunology ; Liver Cirrhosis, Biliary/etiology ; Receptors, Cytoplasmic and Nuclear/physiology ; T-Lymphocytes, Regulatory/immunology ; Vancomycin/pharmacology ; }, abstract = {The tight relationship between the gut and liver on embryological, anatomical and physiological levels inspired the concept of a gut-liver axis as a central element in the pathogenesis of gut-liver axis diseases. This axis refers to the reciprocal regulation between these two organs causing an integrated system of immune homeostasis or tolerance breakdown guided by the microbiota, the diet, genetic background, and environmental factors. Continuous exposure of gut microbiome, various hormones, drugs and toxins, or metabolites from the diet through the portal vein adapt the liver to maintain its tolerogenic state. This is orchestrated by the combined effort of immune cells network: behaving as a sinusoidal and biliary firewall, along with a regulatory network of immune cells including, regulatory T cells and tolerogenic dendritic cells (DC). In addition, downregulation of costimulatory molecules on hepatic sinusoids, hepatocytes and biliary epithelial cells as well as regulating the bile acids chain also play a part in hepatic immune homeostasis. Recent evidence also demonstrated the link between changes in the gut microbiome and liver resident immune cells in the progression of cirrhosis and the tight correlation among primary sclerosing cholangitis (PSC) and also checkpoint induced liver and gut injury. In this review, we will summarize the most recent evidence of the bidirectional relationship among the gut and the liver and how it contributes to liver disease, focusing mainly on PSC and checkpoint induced hepatitis and colitis. We will also focus on completed therapeutic options and on potential targets for future treatment linking with immunology and describe the future direction of this research, taking advantage of modern technologies.}, }
@article {pmid33674230, year = {2021}, author = {Zhou, CB and Zhou, YL and Fang, JY}, title = {Gut Microbiota in Cancer Immune Response and Immunotherapy.}, journal = {Trends in cancer}, volume = {7}, number = {7}, pages = {647-660}, doi = {10.1016/j.trecan.2021.01.010}, pmid = {33674230}, issn = {2405-8025}, mesh = {Adaptive Immunity ; Animals ; Anti-Bacterial Agents/adverse effects ; Combined Modality Therapy/methods ; Disease Models, Animal ; Disease-Free Survival ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*immunology ; Host Microbial Interactions/drug effects/*immunology ; Humans ; Immune Checkpoint Inhibitors/*administration & dosage/adverse effects ; Immunotherapy/methods ; Mice ; Neoplasm Recurrence, Local/*epidemiology/immunology/prevention & control ; Neoplasms/immunology/microbiology/mortality/*therapy ; Prebiotics/administration & dosage ; Probiotics/administration & dosage ; Prognosis ; Progression-Free Survival ; }, abstract = {The gastrointestinal tract (GIT) is the largest immune organ and maintains systemic immune homeostasis in the presence of bacterial challenge. Immune elimination and immune escape are hallmarks of cancer, both of which can be partly bacteria dependent in shaping immunity by mediating host immunomodulation. In addition, host immunity regulates the microbiome by altering bacteria-associated signaling to influence tumor surveillance. Cancer immunotherapy, including immune checkpoint blockade (ICB), appears to have heterogeneous therapeutic effects in different individuals, partially attributed to the microbiota. Thus, the microbiome signature can predict clinical outcomes, prognosis, and immunotherapy responses. In this review, we summarize the intricate crosstalk among the gut microbiome, cancer immune response, and immunotherapy. Interactive modulation of the host microbiota provides new therapeutic strategies to promote anticancer therapy efficacy and/or reduce toxicity.}, }
@article {pmid34912583, year = {2021}, author = {Hollingshead, C and Ciricillo, J and Kammeyer, J}, title = {Ethical Implications of the Fecal Microbiota Transplantation: Disclosure of a False-Positive HIV Test.}, journal = {Case reports in infectious diseases}, volume = {2021}, number = {}, pages = {6696542}, doi = {10.1155/2021/6696542}, pmid = {34912583}, issn = {2090-6625}, abstract = {Fecal microbiota transplantation (FMT) has gained popularity as an effective therapeutic option for Clostridioides difficile infection (CDI). Since its FDA recognition as a treatment modality for recurrent CDI in 2013, screening protocols for FMT donor stool have been in flux. However, extensive health questionnaires, in combination with serological and stool assays, have become mainstays in the donor screening process, although ethical implications are yet to be thoroughly considered. Herein, we present the case of a family member found to have a false-positive HIV test during the donor screening process and discuss potential ethical ramifications associated with FMT stool donation.}, }
@article {pmid34912328, year = {2021}, author = {Liang, M and Liwen, Z and Jianguo, S and Juan, D and Fei, D and Yin, Z and Changping, W and Jianping, C}, title = {Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {728723}, doi = {10.3389/fimmu.2021.728723}, pmid = {34912328}, issn = {1664-3224}, abstract = {Intestinal microbiota (IM) dysbiosis contributes to the development of autoimmune hepatitis (AIH). This study aimed to investigate the potential effect of fecal microbiota transplantation (FMT) in a murine model of experimental AIH (EAH), a condition more similar to that of AIH patients. Changes in the enteric microbiome were determined in AIH patients and EAH mice. Moreover, we established an experimental model of secondary EAH mice harboring dysbiosis (ABx) to analyze the effects of therapeutic FMT administration on follicular regulatory T (TFR) and helper T (TFH) cell imbalances and IM composition in vivo. Alterations of the IM composition and bacterial translocation occurred in AIH patients compared to nonalcoholic fatty liver disease patients and healthy controls (HCs). Therapeutic FMT significantly attenuated liver injury and bacterial translocation and improved the imbalance between splenic TFR cells and TFH cells in ABx EAH mice. Furthermore, therapeutic FMT also partially reversed the increasing trend in serum liver enzymes (ALT and AST) of CXCR5-/-EAH mice on the 28th day. Finally, therapeutic FMT could effectively restore antibiotic-induced IM dysbiosis in EAH mice. Taken together, our findings demonstrated that FMT was capable of controlling hepatitis progression in EAH mice, and the associated mechanism might be involved in the regulation of the TFR/TFH immune imbalance and the restoration of IM composition.}, }
@article {pmid34262150, year = {2021}, author = {Lee, KA and Luong, MK and Shaw, H and Nathan, P and Bataille, V and Spector, TD}, title = {The gut microbiome: what the oncologist ought to know.}, journal = {British journal of cancer}, volume = {125}, number = {9}, pages = {1197-1209}, pmid = {34262150}, issn = {1532-1827}, mesh = {Bacteria/*classification/genetics/immunology ; Diet Therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Neoplasms/immunology/*microbiology/therapy ; Precision Medicine ; Probiotics ; Tumor Microenvironment ; }, abstract = {The gut microbiome (GM) has been implicated in a vast number of human pathologies and has become a focus of oncology research over the past 5 years. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation and protection against pathogens. Strong evidence is emerging to support the effects of the GM on the development of some malignancies but also on responses to cancer therapies, most notably, immune checkpoint inhibition. Tools for manipulating the GM including dietary modification, probiotics and faecal microbiota transfer (FMT) are in development. Current understandings of the many complex interrelationships between the GM, cancer, the immune system, nutrition and medication are ultimately based on a combination of short-term clinical trials and observational studies, paired with an ever-evolving understanding of cancer biology. The next generation of personalised cancer therapies focusses on molecular and phenotypic heterogeneity, tumour evolution and immune status; it is distinctly possible that the GM will become an increasingly central focus amongst them. The aim of this review is to provide clinicians with an overview of microbiome science and our current understanding of the role the GM plays in cancer.}, }
@article {pmid34904826, year = {2021}, author = {Zhao, Y and Chen, X and Shen, J and Xu, A and Wang, Y and Meng, Q and Xu, P}, title = {Black Tea Alleviates Particulate Matter-Induced Lung Injury via the Gut-Lung Axis in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.1c06796}, pmid = {34904826}, issn = {1520-5118}, abstract = {Black tea, as the most consumed kind of tea, is shown to have beneficial effects on human health. However, its impact on particulate matter (PM) induced lung injury and the mechanisms involved have been sparsely addressed. Here, we show that PM-exposed mice exhibited oxidative stress and inflammation in the lungs, which was significantly alleviated by a daily intake of black tea infusion (TI) in a concentration-dependent manner. Interestingly, both the ethanol-soluble fraction (ES) and the ethanol precipitate fraction (EP) exhibited better effects than those of TI; moreover, EP tended to have stronger protection than ES in some indicators, implying that EP played a dominant role in the prevention effects. Furthermore, fecal microbiota transplantation (FMT) revealed that the gut microbiota was differentially reshaped by TI and its fractions were able to directly alleviate the injury induced by PMs. These results indicate that daily intake of black tea and its fractions, especially EP, may alleviate particulate matter-induced lung injury via the gut-lung axis in mice. In addition, the Lachnospiraceae_NK4A136_group could be the core gut microbe contributing to the protection of EP and thus should be further studied in the future.}, }
@article {pmid34896161, year = {2021}, author = {de Souza, JB and Brelaz-de-Castro, MCA and Cavalcanti, IMF}, title = {Strategies for the treatment of colorectal cancer caused by gut microbiota.}, journal = {Life sciences}, volume = {}, number = {}, pages = {120202}, doi = {10.1016/j.lfs.2021.120202}, pmid = {34896161}, issn = {1879-0631}, abstract = {Colorectal cancer (CRC), also named as colon and rectal or bowel cancer, is one of the leading neoplasia diagnosed in the world. Genetic sequencing studies of microorganisms from the intestinal microbiota of patients with CRC revealed that changes in its composition occur with the development of the disease, which can play a fundamental role in its development, being mediated by the production of metabolites and toxins that damage enterocytes. Some microorganisms are frequently reported in the literature as the main agents of this process, such as the bacteria Fusobacterium nucleatum, Escherichia coli and Bacteroides fragilis. Thus, understanding the mechanisms and function of each microorganism in CRC is essential for the development of treatment tools that focus on the gut microbiota. This review verifies current research aimed at evaluating the microorganisms present in the microbiota that can influence the development of CRC, as well as possible forms of treatment that can prevent the initiation and/or spread of this disease. Due to the incidence of CRC, alternatives have been launched considering factors beyond those already known in the disease development, such as diet, fecal microbiota transplantation, use of probiotics and antibiotics, which have been widely studied for this purpose. However, despite being promising, the studies that focus on the development of new therapeutic approaches targeting the microorganisms that cause CRC still need to be improved and better developed, involving new techniques to elucidate the effectiveness and safety of these new methods.}, }
@article {pmid34384521, year = {2021}, author = {Greathouse, KL and Johnson, AJ}, title = {Does caloric restriction prime the microbiome for pathogenic bacteria?.}, journal = {Cell host & microbe}, volume = {29}, number = {8}, pages = {1209-1211}, doi = {10.1016/j.chom.2021.07.009}, pmid = {34384521}, issn = {1934-6069}, mesh = {Animals ; Bacteria/*pathogenicity ; *Caloric Restriction ; Clostridioides difficile ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Mice ; Obesity/microbiology ; Weight Loss ; }, abstract = {A recent study in Nature finds significant shifts in the gut microbiome of post-menopausal women on severe calorie restriction concomitant with weight loss. Microbiota transplantation to germ-free mice display a similar weight loss, along with a bloom in C. difficile, unlocking clues to microbial metabolic alteration in weight loss.}, }
@article {pmid34230217, year = {2022}, author = {Biliński, J and Winter, K and Jasiński, M and Szczęś, A and Bilinska, N and Mullish, BH and Małecka-Panas, E and Basak, GW}, title = {Rapid resolution of COVID-19 after faecal microbiota transplantation.}, journal = {Gut}, volume = {71}, number = {1}, pages = {230-232}, doi = {10.1136/gutjnl-2021-325010}, pmid = {34230217}, issn = {1468-3288}, mesh = {Aged, 80 and over ; COVID-19/complications/diagnosis/*therapy ; Clostridium Infections/complications/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Male ; Young Adult ; }, }
@article {pmid34130227, year = {2021}, author = {Wardill, HR and van der Aa, SAR and da Silva Ferreira, AR and Havinga, R and Tissing, WJE and Harmsen, HJM}, title = {Antibiotic-induced disruption of the microbiome exacerbates chemotherapy-induced diarrhoea and can be mitigated with autologous faecal microbiota transplantation.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {153}, number = {}, pages = {27-39}, doi = {10.1016/j.ejca.2021.05.015}, pmid = {34130227}, issn = {1879-0852}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Diarrhea/*chemically induced ; Fecal Microbiota Transplantation ; Humans ; Microbiota ; Rats ; }, abstract = {BACKGROUND: Chemotherapy is well documented to disrupt the gut microbiome, leading to poor treatment outcomes and a heightened risk of adverse toxicity. Although strong associations exist between its composition and gastrointestinal toxicity, its causal contribution remains unclear. Our inability to move beyond association has limited the development and implementation of microbial-based therapeutics in chemotherapy adjuncts with no clear rationale of how and when to deliver them.
METHODS/RESULTS: Here, we investigate the impact of augmenting the gut microbiome on gastrointestinal toxicity caused by the chemotherapeutic agent, methotrexate (MTX). Faecal microbiome transplantation (FMT) delivered after MTX had no appreciable impact on gastrointestinal toxicity. In contrast, disruption of the microbiome with antibiotics administered before chemotherapy exacerbated gastrointestinal toxicity, impairing mucosal recovery (P < 0.0001) whilst increasing diarrhoea severity (P = 0.0007) and treatment-related mortality (P = 0.0045). Importantly, these detrimental effects were reversed when the microbiome was restored using autologous FMT (P = 0.03), a phenomenon dictated by the uptake and subsequent expansion of Muribaculaceae.
CONCLUSIONS: These are the first data to show that clinically impactful symptoms of gastrointestinal toxicity are dictated by the microbiome and provide a clear rationale for how and when to target the microbiome to mitigate the acute and chronic complications caused by disruption of the gastrointestinal microenvironment. Translation of this new knowledge should focus on stabilising and strengthening the gut microbiome before chemotherapy and developing new microbial approaches to accelerate recovery of the mucosa. By controlling the depth and duration of mucosal injury, secondary consequences of gastrointestinal toxicity may be avoided.}, }
@article {pmid33856024, year = {2021}, author = {Wang, Q and Luo, Y and Ray Chaudhuri, K and Reynolds, R and Tan, EK and Pettersson, S}, title = {The role of gut dysbiosis in Parkinson's disease: mechanistic insights and therapeutic options.}, journal = {Brain : a journal of neurology}, volume = {144}, number = {9}, pages = {2571-2593}, doi = {10.1093/brain/awab156}, pmid = {33856024}, issn = {1460-2156}, mesh = {Brain-Gut Axis/drug effects/*physiology ; Dysbiosis/immunology/*metabolism/*therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Parkinson Disease/immunology/*metabolism/*therapy ; Prebiotics/administration & dosage ; Probiotics/administration & dosage ; }, abstract = {Parkinson's disease is a common neurodegenerative disorder in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alterations in the gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the CNS, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries about alterations to the gut microbiota in Parkinson's disease and focus on current mechanistic insights into the microbiota-gut-brain axis in disease pathophysiology. Moreover, we discuss the interactions between the production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we draw attention to diet modification, the use of probiotics and prebiotics and faecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.}, }
@article {pmid33644835, year = {2021}, author = {Wu, C and Shang, H and Jiang, X and Wang, X and Wei, H}, title = {Application of germ-free NOD-scid IL2rgnull mice as a humanized model for tumor microbiome precision medicine.}, journal = {Science China. Life sciences}, volume = {64}, number = {4}, pages = {644-647}, pmid = {33644835}, issn = {1869-1889}, mesh = {Animals ; *Disease Models, Animal ; Fecal Microbiota Transplantation/methods ; Germ-Free Life/*immunology ; Humans ; Immunotherapy/methods ; Interleukin Receptor Common gamma Subunit/deficiency/genetics/*immunology ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Mice, Transgenic ; Microbiota/*immunology ; Neoplasms/*immunology/microbiology/therapy ; Precision Medicine/*methods ; }, }
@article {pmid34900994, year = {2021}, author = {Rocco, A and Sgamato, C and Compare, D and Coccoli, P and Nardone, OM and Nardone, G}, title = {Gut Microbes and Hepatic Encephalopathy: From the Old Concepts to New Perspectives.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {748253}, doi = {10.3389/fcell.2021.748253}, pmid = {34900994}, issn = {2296-634X}, abstract = {Hepatic encephalopathy (HE) is a severe complication of advanced liver disease and acute liver failure. The clinical spectrum ranges from minor cognitive dysfunctions to lethargy, depressed consciousness, and coma and significantly impact the quality of life, morbidity, and mortality of the patients. It is commonly accepted that the gut milieu is essential for the development of HE; however, despite intensive research efforts, the pathogenesis of HE is still not fully elucidated. As our knowledge of gut microbiota moves from the pioneering era of culture-dependent studies, the connection between microbes, inflammation, and metabolic pathways in the pathogenesis of HE is becoming increasingly clear, providing exciting therapeutic perspectives. This review will critically examine the latest research findings on the role of gut microbes in the pathophysiological pathways underlying HE. Moreover, currently available therapeutic options and novel treatment strategies are discussed.}, }
@article {pmid34900069, year = {2021}, author = {Shi, CY and Yu, CH and Yu, WY and Ying, HZ}, title = {Gut-Lung Microbiota in Chronic Pulmonary Diseases: Evolution, Pathogenesis, and Therapeutics.}, journal = {The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale}, volume = {2021}, number = {}, pages = {9278441}, doi = {10.1155/2021/9278441}, pmid = {34900069}, issn = {1712-9532}, abstract = {The microbiota colonized in the human body has a symbiotic relationship with human body and forms a different microecosystem, which affects human immunity, metabolism, endocrine, and other physiological processes. The imbalance of microbiota is usually linked to the aberrant immune responses and inflammation, which eventually promotes the occurrence and development of respiratory diseases. Patients with chronic respiratory diseases, including asthma, COPD, bronchiectasis, and idiopathic pulmonary fibrosis, often have alteration of the composition and function of intestinal and lung microbiota. Gut microbiota affects respiratory immunity and barrier function through the lung-gut microbiota, resulting in altered prognosis of chronic respiratory diseases. In turn, lung dysbiosis promotes aggravation of lung diseases and causes intestinal dysfunction through persistent activation of lymphoid cells in the body. Recent advances in next-generation sequencing technology have disclosed the pivotal roles of lung-gut microbiota in the pathogenesis of chronic respiratory diseases. This review focuses on the association between the gut-lung dysbiosis and respiratory diseases pathogenesis. In addition, potential therapeutic modalities, such as probiotics and fecal microbiota transplantation, are also evaluated for the prevention of chronic respiratory diseases.}, }
@article {pmid34896553, year = {2021}, author = {Gotoh, K and Sakaguchi, Y and Kato, H and Osaki, H and Jodai, Y and Wakuda, M and Také, A and Hayashi, S and Morita, E and Sugie, T and Ito, Y and Ohmiya, N}, title = {Fecal microbiota transplantation as therapy for recurrent Clostridioides difficile infection is associated with amelioration of delirium and accompanied by changes in fecal microbiota and the metabolome.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {102502}, doi = {10.1016/j.anaerobe.2021.102502}, pmid = {34896553}, issn = {1095-8274}, abstract = {Recurrent Clostridioides difficile infection (rCDI) is a frustrating condition that may affect a person's quality of life for months. Microbiome-based therapy such as fecal microbiota transplantation (FMT) has been effective for the treatment of rCDI by correcting the imbalance of the gut microbiota. Appropriate antibiotic treatment is recommended for at least two recurrences before offering FMT. Here, we report the case of a 92-year-old woman who experienced five recurrences of Clostridioides difficile infection (CDI) (six e