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03 Dec 2021 at 01:43
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Bibliography on: Fecal Transplantation


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RJR: Recommended Bibliography 03 Dec 2021 at 01:43 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2021-12-02

Gao ZY, Cui Z, Yan YQ, et al (2021)

Microbe-based management for colorectal cancer.

Chinese medical journal pii:00029330-900000000-98291 [Epub ahead of print].

ABSTRACT: Colorectal cancer (CRC) is one of the most prevalent, most lethal cancers in the world. Increasing evidence suggests that the intestinal microbiota is closely related to the pathogenesis and prognosis of CRC. The normal microbiota plays an essential role in maintaining gut barrier function and the immune microenvironment. Recent studies have identified carcinogenic bacteria such as enterotoxigenic Bacteroides fragilis (ETBF) and Streptococcus gallolyticus (S. gallolyticus), as well as protective bacterial such as Akkermansia muciniphila (A. muciniphila), as potential targets of CRC treatment. Gut microbiota modulation aims to restore gut dysbiosis, regulate the intestinal immune system and prevent from pathogen invasion, all of which are beneficial for CRC prevention and prognosis. The utility of probiotics, prebiotics, postbiotics, fecal microbiota transplantation and dietary inventions to treat CRC makes them novel microbe-based management tools. In this review, we describe the mechanisms involved in bacteria-derived colorectal carcinogenesis and summarized novel bacteria-related therapies for CRC. In summary, we hope to facilitate clinical applications of intestinal bacteria for preventing and treating CRC.

RevDate: 2021-12-02

Secombe KR, Crame EE, Tam JSY, et al (2021)

Intestinal toll-like receptor 4 knockout alters the functional capacity of the gut microbiome following irinotecan treatment.

Cancer chemotherapy and pharmacology [Epub ahead of print].

PURPOSE: Irinotecan can cause high levels of diarrhea caused by toxic injury to the gastrointestinal microenvironment. Toll-like receptor 4 (TLR4) and the gut microbiome have previously been implicated in gastrointestinal toxicity and diarrhea; however, the link between these two factors has not been definitively determined. We used a tumor-bearing, intestinal epithelial cell (IEC) TLR4 knockout model (Tlr4ΔIEC) to assess microbiome changes following irinotecan treatment. We then determined if a fecal microbiota transplant (FMT) between Tlr4ΔIEC and wild-type (WT) mice altered irinotecan-induced gastrointestinal toxicity.

METHODS: MC-38 colorectal cancer cells were injected into WT and Tlr4ΔIEC mice. Fecal samples were collected prior to tumor inoculation, prior to irinotecan treatment and at cull. 16S rRNA gene sequencing was used to assess changes in the microbiome. Next, FMT was used to transfer the microbiome phenotype between Tlr4ΔIEC and WT mice prior to irinotecan treatment. Gastrointestinal toxicity symptoms were assessed.

RESULTS: In study 1, there were no compositional differences in the microbiome between Tlr4ΔIEC and WT mice at baseline. However, predicted functional capacity of the microbiome was different between WT and Tlr4ΔIEC at baseline and post-irinotecan. In study 2, Tlr4ΔIEC mice were protected from grade 3 diarrhea. Additionally, WT mice who did not receive FMT had more colonic damage in the colon compared to controls (P = 0.013). This was not seen in Tlr4ΔIEC mice or WT mice who received FMT (P > 0.05).

CONCLUSION: Tlr4ΔIEC and WT had no baseline compositional microbiome differences, but functional differences at baseline and following irinotecan. FMT altered some aspects of irinotecan-induced gastrointestinal toxicity.

RevDate: 2021-12-02

Dodiya HB, Lutz HL, Weigle IQ, et al (2022)

Gut microbiota-driven brain Aβ amyloidosis in mice requires microglia.

The Journal of experimental medicine, 219(1):.

We previously demonstrated that lifelong antibiotic (ABX) perturbations of the gut microbiome in male APPPS1-21 mice lead to reductions in amyloid β (Aβ) plaque pathology and altered phenotypes of plaque-associated microglia. Here, we show that a short, 7-d treatment of preweaned male mice with high-dose ABX is associated with reductions of Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes at 9 wk of age in male mice only. More importantly, fecal microbiota transplantation (FMT) from transgenic (Tg) or WT male donors into ABX-treated male mice completely restored Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes. Transcriptomic studies revealed significant differences between vehicle versus ABX-treated male mice and FMT from Tg mice into ABX-treated mice largely restored the transcriptome profiles to that of the Tg donor animals. Finally, colony-stimulating factor 1 receptor (CSF1R) inhibitor-mediated depletion of microglia in ABX-treated male mice failed to reduce cerebral Aβ amyloidosis. Thus, microglia play a critical role in driving gut microbiome-mediated alterations of cerebral Aβ deposition.

RevDate: 2021-12-02

Jena R, Jain R, Muralidharan S, et al (2021)

Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Parkinson's Disease.

Cureus, 13(10):e19035.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases with a high rate of morbidity. It is associated with dopaminergic neuron loss and is fairly common in the elderly population. Recently, there has been a growing interest in the role of the gut microbiome in the pathogenesis of PD and thus studies addressing the methods to modulate the microbiota are becoming increasingly popular. Fecal microbiota transplant (FMT) is one of these methods and is effective in certain intestinal and extraintestinal conditions. This review aims to talk about gastrointestinal dysbiosis and how the reconstruction of this microbiome via FMT could potentially be used as a treatment modality in the future. We went through various studies and collected data relevant to our topic from the previous five years. The studies selected include reviews, observational studies, animal studies, case reports, and some grey literature. We concluded that although it has great potential as a therapeutic modality in the future, it is limited by several factors such as variability among the results of most clinical studies and the lack of large sample sizes. Therefore, there is a need for high-quality clinical trials with larger sample sizes to gather enough clinical evidence so that FMT can qualify as a widely recommended therapeutic measure.

RevDate: 2021-12-02

Chen HL, Zeng YB, Zhang ZY, et al (2021)

Gut and Cutaneous Microbiome Featuring Abundance of Lactobacillus reuteri Protected Against Psoriasis-Like Inflammation in Mice.

Journal of inflammation research, 14:6175-6190 pii:337031.

Background: Psoriasis is a chronic autoinflammatory skin disease, and its aetiology remains incompletely understood. Recently, gut microbial dysbiosis is found to be tightly associated with psoriasis.

Objective: We sought to reveal the causal role of gut microbiota dysbiosis in psoriasis pathogenesis and investigate the protective effect of healthy commensal bacteria against imiquimod -induced psoriasis-like skin response.

Methods: By using fecal microbial transplantation (FMT), 16S rRNA gene-based taxonomic profiling and Lactobacillus supplement, we have assessed the effect of FMT from healthy individuals on psoriasis-like skin inflammation and associated immune disorders in imiquimod-induced psoriasis mice.

Results: Here, by using psoriasis mice humanized with the stools from healthy donors and psoriasis patients, the imiquimod-induced psoriasis in mice with psoriasis patient stool was found to be significantly aggravated as compared to the mice with healthy donor stools. Further analysis showed fecal microbiota of healthy individuals protected against Treg/Th17 imbalance in psoriasis. Moreover, we found the gut and skin microbiome in mice receipted with gut microbiota of healthy individuals (HD) differed from those of mice receipted with gut microbiota of psoriasis patients (PSD). 16S rRNA sequencing revealed that Lactobacillus reuteri was greatly enriched in fecal and cutaneous microbiome of HD mice as compared to PSD mice. Intriguingly, supplement with Lactobacillus reuteri was sufficient to increase the expression of anti-inflammatory gene IL-10, reduce Th17 cells counts and confer resistance to imiquimod-induced inflammation on the mice with gut microbiota dysbiosis.

Conclusion: Our results suggested that the gut microbiota dysbiosis is the potential causal factor for psoriasis and the gut microbiota may serve as promising therapy target for psoriasis patients.

RevDate: 2021-12-02

Xie L, Xu C, Fan Y, et al (2021)

Effect of fecal microbiota transplantation in patients with slow transit constipation and the relative mechanisms based on the protein digestion and absorption pathway.

Journal of translational medicine, 19(1):490.

BACKGROUND: Fecal microbiota transplantation (FMT) is considered an effective treatment for slow transit constipation (STC); nevertheless, the mechanism remains unclear.

METHODS: In this study, eight patients with STC were selected according to the inclusion and exclusion criteria; they then received three treatments of FMT. The feces and serum of STC patients were collected after each treatment and analyzed by integrating 16 s rRNA microbiome and metabolomic analyses.

RESULTS: The results showed that the percentage of clinical improvement reached 62.5% and the rates of patients' clinical remission achieved 75% after the third treatment. At the same time, FMT improved the Wexner constipation scale (WCS), the Gastrointestinal Quality-of-Life Index (GIQLI) and Hamilton Depression Scale (HAMD). Fecal microbiome alpha diversity and beta diversity altered significantly after FMT. Analysis of the 16 s rRNA microbiome showed that the numbers of Bacteroidetes (Prevotell/Bacteroides) and Firmicute (Roseburia/Blautia) decreased, whereas Actinobacteria (Bifidobacterium), Proteobacteria (Escherichia), and Firmicute (Lactobacillus) increased after FMT. The metabolomics analyses showed that the stool of FMT-treated patients were characterized by relatively high levels of N-Acetyl-L-glutamate, gamma-L-glutamyl-L-glutamic acid, Glycerophosphocholine, et al., after FMT. Compared with baseline, the serum of treated patients was characterized by relatively high levels of L-Arginine, L-Threonine, Ser-Arg, Indoleacrylic acid, Phe-Tyr, 5-L-Glutamyl-L-alanine, and lower levels of Erucamide after the treatment. The correlation analysis between the metabolites and gut microbiota showed a significant correlation. For example, L-Arginine was positively correlated with lactobacillus, et al. L-Threonine was positively correlated with Anaerovibrio, Sediminibacterium but negatively correlated with Phascolarctobacterium. Erucamide had significant negative correlations with Sediminibacterium and Sharpea, while being positively correlated with Phascolarctobacterium. Enriched KEGG pathways analysis demonstrated that the protein digestion and absorption pathways gradually upregulated with the increase of FMT frequency. The L-Arginine and L-Threonine were also involved in the pathway. A large amount of Na + was absorbed in the pathway, so that it might increase mucus secretion and electrical excitability of GI smooth muscle.

CONCLUSIONS: Therefore, we speculated that FMT changed the patients' gut microbiota and metabolites involved in the protein digestion and absorption pathways, thereby improving the symptoms of STC. Study on the effectiveness and safety of FMT in the treatment of STC. The study was reviewed and approved by Ethics Committee of Tianjin People's Hospital (ChiCTR2000033227) in 2020.

RevDate: 2021-11-30
CmpDate: 2021-11-30

Kang Y, Kang X, Zhang H, et al (2021)

Gut Microbiota and Parkinson's Disease: Implications for Faecal Microbiota Transplantation Therapy.

ASN neuro, 13:17590914211016217.

Parkinson's disease (PD) ranks the second place among neurodegenerative diseases in terms of its morbidity, which affects 1-2% people aged over 65 years. In addition to genetics, some environmental factors may exert vital parts in PD occurrence as well. At present, more and more studies are conducted to elucidate the association between gut microbial dysbiosis and the incidence of PD. Gut microbial dysbiosis has a certain effect on both the central nervous system (CNS) and the enteric nervous system (ENS), which indicates that there is a gut-microbiota-brain axis that induces CNS disorders. Some gut microbial strains are suggested to suppress or weaken the neuroinflammation- and gut-inflammation-immune responses, which suggests the protective and pathogenic effects of certain gut microbial species on PD progression. Therefore, gut microbiome may contain plenty of targets for preventing and managing PD. Faecal microbiota transplantation (FMT) may serve as a direct and useful treatment for PD in the future. Nonetheless, there is little available scientific research in this field. The present work reviewed the latest research to examine the association of gut microbiota with PD, and the future prospects of FMT treatment.

RevDate: 2021-11-30
CmpDate: 2021-11-30

Constante M, De Palma G, Lu J, et al (2021)

Saccharomyces boulardii CNCM I-745 modulates the microbiota-gut-brain axis in a humanized mouse model of Irritable Bowel Syndrome.

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society, 33(3):e13985.

BACKGROUND: Gnotobiotic mice colonized with microbiota from patients with irritable bowel syndrome (IBS) and comorbid anxiety (IBS+A) display gut dysfunction and anxiety-like behavior compared to mice colonized with microbiota from healthy volunteers. Using this model, we tested the therapeutic potential of the probiotic yeast Saccharomyces boulardii strain CNCM I-745 (S. bou) and investigated underlying mechanisms.

METHODS: Germ-free Swiss Webster mice were colonized with fecal microbiota from an IBS+A patient or a healthy control (HC). Three weeks later, mice were gavaged daily with S. boulardii or placebo for two weeks. Anxiety-like behavior (light preference and step-down tests), gastrointestinal transit, and permeability were assessed. After sacrifice, samples were taken for gene expression by NanoString and qRT-PCR, microbiota 16S rRNA profiling, and indole quantification.

KEY RESULTS: Mice colonized with IBS+A microbiota developed faster gastrointestinal transit and anxiety-like behavior (longer step-down latency) compared to mice with HC microbiota. S. bou administration normalized gastrointestinal transit and anxiety-like behavior in mice with IBS+A microbiota. Step-down latency correlated with colonic Trpv1 expression and was associated with altered microbiota profile and increased Indole-3-acetic acid (IAA) levels.

CONCLUSIONS & INFERENCES: Treatment with S. bou improves gastrointestinal motility and anxiety-like behavior in mice with IBS+A microbiota. Putative mechanisms include effects on pain pathways, direct modulation of the microbiota, and indole production by commensal bacteria.

RevDate: 2021-11-29

Wei K, T Chen (2021)

[Vaginal microbiota transplantation for treatment of bacterial vaginosis: a review].

Sheng wu gong cheng xue bao = Chinese journal of biotechnology, 37(11):3820-3827.

Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. The conventional antibiotic treatment can aggravate microbial dysbiosis, alter the acid environment of the vagina and lead to drug resistance, thus shows low cure rate and high recurrence rate. This poses significant physiological and psychological burden to the BV patients. Vaginal microbiota transplantation (VMT) is a novel live biotherapeutic approach. It directly engrafts the whole vaginal microbiota from healthy women to the vaginal tract of patients to rapidly reconstruct the vaginal microbiota environment and restore the vaginal health. This article summarizes the development, present challenges, and future directions of using VMT, with the aim to explore new strategies for treatment of BV and promote the clinical use of VMT.

RevDate: 2021-11-29

Zhang M, Wang H, Xue L, et al (2021)

[Advances in fecal microbiota transplantation for treatment of Parkinson's disease].

Sheng wu gong cheng xue bao = Chinese journal of biotechnology, 37(11):3812-3819.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Patients with PD often suffer from gastrointestinal symptoms in the early stage of the disease. Several studies have confirmed that gut microbiota is involved in the progress of PD. As one of the most effective ways to reconstruct the gut microbiota, fecal microbiota transplantation (FMT) has shown potential therapeutic effects on PD. This review summarizes the basic and clinical studies of FMT in the treatment of PD.

RevDate: 2021-11-29

Hiltunen H, Hanani H, Luoto R, et al (2021)

Preterm infant meconium microbiota transplant induces growth failure, inflammatory activation, and metabolic disturbances in germ-free mice.

Cell reports. Medicine, 2(11):100447 pii:S2666-3791(21)00315-3.

Preterm birth may result in adverse health outcomes. Very preterm infants typically exhibit postnatal growth restriction, metabolic disturbances, and exaggerated inflammatory responses. We investigated the differences in the meconium microbiota composition between very preterm (<32 weeks), moderately preterm (32-37 weeks), and term (>37 weeks) human neonates by 16S rRNA gene sequencing. Human meconium microbiota transplants to germ-free mice were conducted to investigate whether the meconium microbiota is causally related to the preterm infant phenotype in an experimental model. Our results indicate that very preterm birth is associated with a distinct meconium microbiota composition. Fecal microbiota transplant of very preterm infant meconium results in impaired growth, altered intestinal immune function, and metabolic parameters as compared to term infant meconium transplants in germ-free mice. This finding suggests that measures aiming to minimize the long-term adverse consequences of very preterm birth should be commenced during pregnancy or directly after birth.

RevDate: 2021-11-29

Gunardi TH, Susantono DP, Victor AA, et al (2021)

Atopobiosis and Dysbiosis in Ocular Diseases: Is Fecal Microbiota Transplant and Probiotics a Promising Solution?.

Journal of ophthalmic & vision research, 16(4):631-643.

Purpose: To highlight the role of atopobiosis and dysbiosis in the pathomechanism of autoimmune uveitis, therefore supporting fecal microbiota transplant (FMT) and probiotics as potential targeted-treatment for uveitis.

Methods: This review synthesized literatures upon the relation between gut microbiota, autoimmune uveitis, FMT, and probiotics, published from January 2001 to March 2021 and indexed in PubMed, Google Scholar, CrossRef.

Results: The basis of the gut-eye axis revolves around occurrences of molecular mimicry, increase in pro-inflammatory cytokines, gut epithelial barrier disruption, and translocation of microbes to distant sites. In patients with autoimmune uveitis, an increase of gut Fusobacterium and Enterobacterium were found. With current knowledge of aforementioned mechanisms, studies modifying the gut microbiome and restoring the physiologic gut barrier has been the main focus for pathomechanism-based therapy. In mice models, FMT and probiotics targeting repopulation of gut microbiota has shown significant improvement in clinical manifestations of uveitis. Consequently, a better understanding in the homeostasis of gut microbiome along with their role in the gut-eye axis is needed to develop practical targeted treatment.

Conclusion: Current preliminary studies are promising in establishing a causative gut-eye axis relationship and the possibility of conducting FMT and probiotics as targeted treatment to mitigate autoimmune uveitis, to shorten disease duration, and to prevent further complications.

RevDate: 2021-11-29
CmpDate: 2021-11-29

Sun D, Bai R, Zhou W, et al (2021)

Angiogenin maintains gut microbe homeostasis by balancing α-Proteobacteria and Lachnospiraceae.

Gut, 70(4):666-676.

OBJECTIVE: Antimicrobial peptides (AMPs) play essential roles in maintaining gut health and are associated with IBD. This study is to elucidate the effect of angiogenin (ANG), an intestine-secreted AMP, on gut microbiota and its relevance with IBD.

DESIGN: The effect of ANG on microbiota and its contribution to colitis were evaluated in different colitis models with co-housing and faecal microbiota transplantation. ANG-regulated bacteria were determined by 16S rDNA sequencing and their functions in colitis were analysed by bacterial colonisation. The species-specific antimicrobial activity of ANG and its underlying mechanism were further investigated with microbiological and biochemical methods. ANG level and the key bacteria were characterised in IBD faecal samples.

RESULTS: ANG regulated microbiota composition and inhibited intestinal inflammation. Specifically, Ang1 deficiency in mice led to a decrease in the protective gut commensal strains of Lachnospiraceae but an increase in the colitogenic strains of α-Proteobacteria. Direct binding of ANG to α-Proteobacteria resulted in lethal disruption of bacterial membrane integrity, and consequently promoted the growth of Lachnospiraceae, which otherwise was antagonised by α-Proteobacteria. Oral administration of ANG1 reversed the dysbiosis and attenuated the severity of colitis in Ang1-deficient mice. The correlation among ANG, the identified bacteria and IBD status was established in patients.

CONCLUSION: These findings demonstrate a novel role of ANG in shaping gut microbe composition and thus maintaining gut health, suggesting that the ANG-microbiota axis could be developed as a potential preventive and/or therapeutic approach for dysbiosis-related gut diseases.

RevDate: 2021-11-29
CmpDate: 2021-11-29

Zhang X, Coker OO, Chu ES, et al (2021)

Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites.

Gut, 70(4):761-774.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is an increasing healthcare burden worldwide. We examined the role of dietary cholesterol in driving NAFLD-HCC through modulating gut microbiota and its metabolites.

DESIGN: High-fat/high-cholesterol (HFHC), high-fat/low-cholesterol or normal chow diet was fed to C57BL/6 male littermates for 14 months. Cholesterol-lowering drug atorvastatin was administered to HFHC-fed mice. Germ-free mice were transplanted with stools from mice fed different diets to determine the direct role of cholesterol modulated-microbiota in NAFLD-HCC. Gut microbiota was analysed by 16S rRNA sequencing and serum metabolites by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. Faecal microbial compositions were examined in 59 hypercholesterolemia patients and 39 healthy controls.

RESULTS: High dietary cholesterol led to the sequential progression of steatosis, steatohepatitis, fibrosis and eventually HCC in mice, concomitant with insulin resistance. Cholesterol-induced NAFLD-HCC formation was associated with gut microbiota dysbiosis. The microbiota composition clustered distinctly along stages of steatosis, steatohepatitis and HCC. Mucispirillum, Desulfovibrio, Anaerotruncus and Desulfovibrionaceae increased sequentially; while Bifidobacterium and Bacteroides were depleted in HFHC-fed mice, which was corroborated in human hypercholesteremia patients. Dietary cholesterol induced gut bacterial metabolites alteration including increased taurocholic acid and decreased 3-indolepropionic acid. Germ-free mice gavaged with stools from mice fed HFHC manifested hepatic lipid accumulation, inflammation and cell proliferation. Moreover, atorvastatin restored cholesterol-induced gut microbiota dysbiosis and completely prevented NAFLD-HCC development.

CONCLUSIONS: Dietary cholesterol drives NAFLD-HCC formation by inducing alteration of gut microbiota and metabolites in mice. Cholesterol inhibitory therapy and gut microbiota manipulation may be effective strategies for NAFLD-HCC prevention.

RevDate: 2021-11-27

Lee PC, Chang TE, Wang YP, et al (2021)

Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection.

Journal of the Formosan Medical Association = Taiwan yi zhi pii:S0929-6646(21)00498-8 [Epub ahead of print].

BACKGROUND/PURPOSE: Clostridium difficile infection (CDI) leads to a significant cause of hospital-acquired morbidity and mortality. Fecal microbiota transplantation (FMT) is effective to treat recurrent or refractory CDI (rCDI). However, the change of microbial composition contributed by FMT and its association with treatment outcomes is not well determined in Taiwan. We aimed to investigate the efficacy of FMT and the association with microbial alteration endemically.

METHODS: Twelve patients who received FMT for rCDI in Taipei Veterans General Hospital were prospectively enrolled from April 2019 to July 2020. The clinical assessments and fecal microbial analyses in comparison with fecal materials of unrelated donors were conducted before and after FMT.

RESULTS: The overall success rate of FMT for rCDI was 91.7%. A prominence of Proteobacteria, Gammaproteobacteria and Enterobacteriales were observed in the feces of patients with rCDI. Increased fecal phylogenetic diversities and a significant microbial dissimilarity were provided by successful FMT compared to patients before treatment. However, the distinctness was not obvious between patients' feces at baseline and after unsuccessful FMT. Moreover, dynamic change of fecal microbial composition after FMT was observed during follow-up but did not interrupt the treatment effects of FMT.

CONCLUSION: Gut dysbiosis commonly co-exists in patients with rCDI. Restoration of gut microbial communities by FMT provides a promising strategy to treat antibiotic-failed CDI, and the extent of microbial change would be related to the treatment outcomes of FMT. Besides, the effectiveness of FMT for CDI could be maintained even the gut microbiota has diverged over time.

RevDate: 2021-11-27

Houron C, Ciocan D, Trainel N, et al (2021)

Gut Microbiota Reshaped by Pectin Treatment Improves Liver Steatosis in Obese Mice.

Nutrients, 13(11): pii:nu13113725.

Pectin, a soluble fiber, improves non-alcoholic fatty-liver disease (NAFLD), but its mechanisms are unclear. We aimed to investigate the role of pectin-induced changes in intestinal microbiota (IM) in NAFLD. We recovered the IM from mice fed a high-fat diet, treated or not with pectin, to perform a fecal microbiota transfer (FMT). Mice fed a high-fat diet, which induces NAFLD, were treated with pectin or received a fecal microbiota transfer (FMT) from mice treated with pectin before (preventive FMT) or after (curative FMT) being fed a high-fat diet. Pectin prevented the development of NAFLD, induced browning of adipose tissue, and modified the IM without increasing the abundance of proteobacteria. Preventive FMT also induced browning of white adipose tissue but did not improve liver steatosis, in contrast to curative FMT, which induced an improvement in steatosis. This was associated with an increase in the concentration of short-chain fatty acids (SCFAs), in contrast to preventive FMT, which induced an increase in the concentration of branched SCFAs. Overall, we show that the effect of pectin may be partially mediated by gut bacteria.

RevDate: 2021-11-27

Sun P, Su L, Zhu H, et al (2021)

Gut Microbiota Regulation and Their Implication in the Development of Neurodegenerative Disease.

Microorganisms, 9(11): pii:microorganisms9112281.

In recent years, human gut microbiota have become one of the most promising areas of microorganism research; meanwhile, the inter-relation between the gut microbiota and various human diseases is a primary focus. As is demonstrated by the accumulating evidence, the gastrointestinal tract and central nervous system interact through the gut-brain axis, which includes neuronal, immune-mediated and metabolite-mediated pathways. Additionally, recent progress from both preclinical and clinical studies indicated that gut microbiota play a pivotal role in gut-brain interactions, whereas the imbalance of the gut microbiota composition may be associated with the pathogenesis of neurological diseases (particularly neurodegenerative diseases), the underlying mechanism of which is insufficiently studied. This review aims to highlight the relationship between gut microbiota and neurodegenerative diseases, and to contribute to our understanding of the function of gut microbiota in neurodegeneration, as well as their relevant mechanisms. Furthermore, we also discuss the current application and future prospects of microbiota-associated therapy, including probiotics and fecal microbiota transplantation (FMT), potentially shedding new light on the research of neurodegeneration.

RevDate: 2021-11-27

Monaghan TM, Duggal NA, Rosati E, et al (2021)

A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection.

Cells, 10(11): pii:cells10113234.

Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.

RevDate: 2021-11-27

Eindor-Abarbanel A, Healey GR, K Jacobson (2021)

Therapeutic Advances in Gut Microbiome Modulation in Patients with Inflammatory Bowel Disease from Pediatrics to Adulthood.

International journal of molecular sciences, 22(22): pii:ijms222212506.

There is mounting evidence that the gut microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD). For the past decade, high throughput sequencing-based gut microbiome research has identified characteristic shifts in the composition of the intestinal microbiota in patients with IBD, suggesting that IBD results from alterations in the interactions between intestinal microbes and the host's mucosal immune system. These studies have been the impetus for the development of new therapeutic approaches targeting the gut microbiome, such as nutritional therapies, probiotics, fecal microbiota transplant and beneficial metabolic derivatives. Innovative technologies can further our understanding of the role the microbiome plays as well as help to evaluate how the different approaches in microbiome modulation impact clinical responses in adult and pediatric patients. In this review, we highlight important microbiome studies in patients with IBD and their response to different microbiome modulation therapies, and describe the differences in therapeutic response between pediatric and adult patient cohorts.

RevDate: 2021-11-24

Chang CS, Liao YC, Huang CT, et al (2021)

Identification of a gut microbiota member that ameliorates DSS-induced colitis in intestinal barrier enhanced Dusp6-deficient mice.

Cell reports, 37(8):110016.

Strengthening the gut epithelial barrier is a potential strategy for management of gut microbiota-associated illnesses. Here, we demonstrate that dual-specificity phosphatase 6 (Dusp6) knockout enhances baseline colon barrier integrity and ameliorates dextran sulfate sodium (DSS)-induced colonic injury. DUSP6 mutation in Caco-2 cells enhances the epithelial feature and increases mitochondrial oxygen consumption, accompanied by altered glucose metabolism and decreased glycolysis. We find that Dusp6-knockout mice are more resistant to DSS-induced dysbiosis, and the cohousing and fecal microbiota transplantation experiments show that the gut/fecal microbiota derived from Dusp6-knockout mice also confers protection against colitis. Further culturomics and mono-colonialization experiments show that one gut microbiota member in the genus Duncaniella confers host protection from DSS-induced injury. We identify Dusp6 deficiency as beneficial for shaping the gut microbiota eubiosis necessary to protect against gut barrier-related diseases.

RevDate: 2021-11-24

Michailidis L, Currier AC, Le M, et al (2021)

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies.

Annals of gastroenterology, 34(6):802-814.

Background: Fecal microbiota transplantation (FMT) has shown excellent efficacy in treating Clostridioides difficile infection, as well as promise in several other diseases. The heightened interest is accompanied by concerns over adverse events (AE) and safety. To further understand that in FMT, we performed a systematic review of the literature and a meta-analysis of high-quality, prospective randomized controlled trials FMT.

Methods: Studies were selected based on predefined exclusion criteria and were assessed for quality. Only prospective, randomized, controlled studies of high quality were included in the final analysis. Data were extracted on demographics, AE, indication, delivery method and follow-up duration.

Results: Out of 334 articles reviewed, 9 high quality studies with 756 FMTs were selected for final analysis. The pooled rate of AE was 39.3% (95% confidence interval [CI] 0.19-0.642) as they were reported by 112 patients who received FMT. The SAE rate was 5.3% (95%CI 3.1-8.8%). The most common AE reported was abdominal pain, followed by diarrhea. The most common SAE was Clostridium difficile infection. Upper gastrointestinal tract delivery was associated with a higher rate of total AE, but not SAE.

Conclusions: Based on the selected studies, the AE rate of FMT is 39.3%, with most AE being mild and self-limiting. SAE were uncommon at 5.3%, and many were only possibly related to the FMT. Adherence to standardized reporting of AE as well as longitudinal studies and registries will help further clarify the safety of FMT in the future.

RevDate: 2021-11-23

Ma Y, Guo R, Sun Y, et al (2021)

Lupus gut microbiota transplants cause autoimmunity and inflammation.

Clinical immunology (Orlando, Fla.) pii:S1521-6616(21)00229-1 [Epub ahead of print].

BACKGROUND: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16 s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free (GF) mice.

RESULTS: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to GF mice caused GF mice to develop a series of lupus-like phenotypic features, including increased serum autoimmune antibodies, imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants.

CONCLUSIONS: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.

RevDate: 2021-11-23

Zhilu X, Xiangqian D, Keli Y, et al (2021)

Association of Adherent-invasive Escherichia coli with severe Gut Mucosal dysbiosis in Hong Kong Chinese population with Crohn's disease.

Gut microbes, 13(1):1994833.

Adherent invasive Escherichia Coli (AIEC) has been implicated in the pathogenesis of Crohn's disease (CD) in Western populations. Whether the presence of AIEC is also seen in CD populations of different genetic susceptibility and has negative impact on host microbiota ecology and therapeutics are unclear. AIEC presence was assessed in ileal tissues of 60 Hong Kong Chinese patients with CD and 56 healthy subjects. Mucosa microbiota was analyzed by 16s rRNA sequencing. Impact of AIEC on the gut microbiota was determined in a mouse model. AIEC was significantly more prevalent in ileal tissues of patients with CD than controls (30% vs 7.1%). Presence of AIEC in ileal tissues was associated with more severe mucosa microbiota dysbiosis in CD with decreased diversity and lower abundance of Firmicutes including butyrate producing Roseburia and probiotic Bacillus. A random forest model predicted the presence of AIEC with area under the curve of 0.89. AIEC exacerbated dysbiosis in dextran sodium sulfate (DSS)-induced colitis mice and led to resistance to restoration of normal gut microbiota by fecal microbiota transplantation (FMT). Proportion of donor-derived bacteria in AIEC-colonized mice was significantly lower than that in uninfected mice. AIEC was prevalent and associated with severe mucosa microbiota dysbiosis in CD in Hong Kong Chinese population. The presence of AIEC impeded restoration of normal gut microbiota. AIEC may serve as a keystone bacterium in CD and impact the efficacy of FMT.

RevDate: 2021-11-22

Mu C, Pi Y, Zhang C, et al (2022)

Microbiomes in the Intestine of Developing Pigs: Implications for Nutrition and Health.

Advances in experimental medicine and biology, 1354:161-176.

The past decade has seen an expansion of studies on the role of gut microbiome in piglet nutrition and health. With the help of culture-independent sequencing techniques, the colonization of gut microbiota and their implication in physiology are being investigated in depth. Immediately after birth, the microbes begin to colonize following an age-dependent trajectory, which can be modified by maternal environment, diet, antibiotics, and fecal microbiota transplantation. The early-life gut microbiome is relatively simple but enriched with huge metabolic potential to utilize milk oligosaccharides and affect the epithelial function. After weaning, the gut microbiome develops towards a gradual adaptation to the introduction of solid food, with an enhanced ability to metabolize amino acids, fibers, and bile acids. Here we summarize the compositional and functional difference of the gut microbiome in the keystone developing phases, with a specific focus on the use of different nutritional approaches based on the phase-specific gut microbiome.

RevDate: 2021-11-22

Yang J, Xiong P, Bai L, et al (2021)

The Association of Altered Gut Microbiota and Intestinal Mucosal Barrier Integrity in Mice With Heroin Dependence.

Frontiers in nutrition, 8:765414.

The gut microbiota is believed to play a significant role in psychological and gastrointestinal symptoms in heroin addicts. However, the underlying mechanism remains largely unknown. We show here that heroin addicts had a decrease in body mass index (BMI) and abnormal serum D-lactic acid (DLA), endotoxin (ET) and diamine oxidase (DAO) levels during their withdrawal stage, suggesting a potential intestinal injury. The gut microbial profiles in the mouse model with heroin dependence showed slightly decreased alpha diversity, as well as higher levels of Bifidobacterium and Sutterella and a decrease in Akkermansia at genus level compared to the control group. Fecal microbiota transplantation (FMT) further confirmed that the microbiota altered by heroin dependence was sufficient to impair body weight and intestinal mucosal barrier integrity in recipient mice. Moreover, short-chain fatty acids (SCFAs) profiling revealed that microbiota-derived propionic acid significantly decreased in heroin dependent mice compared to controls. Overall, our study shows that heroin dependence significantly altered gut microbiota and impaired intestinal mucosal barrier integrity in mice, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.

RevDate: 2021-11-22

Hazan S, Dave S, Papoutsis AJ, et al (2021)

Successful Bacterial Engraftment Identified by Next-Generation Sequencing Predicts Success of Fecal Microbiota Transplant for Clostridioides difficile.

Gastroenterology research, 14(5):304-309.

Background: The effectiveness of fecal microbiota transplantation (FMT), a treatment for Clostridioides difficile infection (CDI), is dependent on successful engraftment (incorporation) of donor stool. We present a method for evaluating engraftment success based on next-generation sequencing (NGS)-based profiling of bacterial strains present in donor and recipient stool, and we suggest its potential to guide treatment decisions.

Methods: Bacterial strains in stool samples from three patients from the clinic and one donor were analyzed via NGS and metagenomic sequencing, before and 1 month after FMT for CDI. The similarity of strains present was assessed via relative abundance, principal component analysis, Shannon and Simpson diversity indexes, and Bray-Curtis dissimilarity matrix. A positive outcome was successful engraftment, where the post-FMT sample closely resembled that of the donor and CDI was cured.

Results: Patients (Pts.) 1 and 2, but not Pt. 3's stool samples closely resembled the donor specimen post-FMT. Noteworthy, Pt. 3 pre-FMT sample was less similar to the donor than that of Pts. 1 and 2. All methods of assessing similarity and dissimilarity used yielded virtually identical conclusions. Pts. 1 and 2 which closely resembled donor specimen, eradicated CDI giving a surrogate objective measure of engraftment.

Conclusions: Success of engraftment in FMT can be assessed using NGS and metagenomic analysis and parallels success in curing CDI of the microbiome. The statistical methods we present here are reliable and consistent for such purposes. The dissimilarity of Pt. 3 to the donor combined with the failure of engraftment and failure to cure CDI in Pt. 3 suggests that FMT success may be predictable by comparing pre-FMT samples to donor. There is no clinical trial registry listing this study.

RevDate: 2021-11-22

Sun Y, Xie R, Li L, et al (2021)

Prenatal Maternal Stress Exacerbates Experimental Colitis of Offspring in Adulthood.

Frontiers in immunology, 12:700995.

The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.

RevDate: 2021-11-22

Wang Y, Zhang J, Xu L, et al (2021)

Modified Gegen Qinlian Decoction Regulates Treg/Th17 Balance to Ameliorate DSS-Induced Acute Experimental Colitis in Mice by Altering the Gut Microbiota.

Frontiers in pharmacology, 12:756978 pii:756978.

Inflammatory bowel disease (IBD) is characterized by chronic pathology associated with extensive intestinal microbial dysregulation and intestinal inflammation. Thus, efforts are underway to manipulate the gut microbiome to improve inflammatory pathology. Gegen Qinlian decoction (GQD), a traditional Chinese medicine prescription, has been widely utilized for treating diarrhea and ulcerative colitis (UC) for thousands of years. However, the underlying mechanism of its efficacy and whether its protective effect against colitis is mediated by the gut microbiota are poorly understood. In the present study, our data demonstrated that modified GQD (MGQD) administration significantly improved the pathological phenotypes and colonic inflammation challenged by DSS in mice, which were specifically manifested as reduced loss of body weight, shortening of colon length, DAI score, histological score and suppressed inflammatory response. 16S rRNA sequencing and targeted metabonomics analysis showed that MQGD altered the diversity and community landscape of the intestinal microbiota and the metabolic profiles. In particular, MQGD significantly boosted the abundance of the intestinal microbiota producing short-chain fatty acids (SCFAs), which are causally associated with promoting the development of Treg cells and suppressing the differentiation of pro-inflammatory Th17 cells. More importantly, transferring fecal microbiota from MGQD-treated or healthy controls exhibited equivalent alleviative effects on colitis mice. However, this protective effect could not be replicated in experiments of mice with depleted intestinal microbes through broad-spectrum antibiotic cocktails (ABX), further supporting the importance of SCFA-producing gut microbiota in the beneficial role of MGQD. In general, MGQD therapy has the potential to remodel the intestinal microbiome and reestablish immune homeostasis to ameliorate DSS-induced colitis.

RevDate: 2021-11-22

Amedei A, Capasso C, Nannini G, et al (2021)

Microbiota, Bacterial Carbonic Anhydrases, and Modulators of Their Activity: Links to Human Diseases?.

Mediators of inflammation, 2021:6926082.

The involvement of the human microbiome is crucial for different host functions such as protection, metabolism, reproduction, and especially immunity. However, both endogenous and exogenous factors can affect the balance of the microbiota, creating a state of dysbiosis, which can start various gastrointestinal or systemic diseases. The challenge of future medicine is to remodel the intestinal microbiota to bring it back to healthy equilibrium (eubiosis) and, thus, counteract its negative role in the diseases' onset. The shaping of the microbiota is currently practiced in different ways ranging from diet (or use of prebiotics, probiotics, and synbiotics) to phage therapy and antibiotics, including microbiota fecal transplantation. Furthermore, because microbiota modulation is a capillary process, and because many microbiota bacteria (both beneficial and pathogenic) have carbonic anhydrases (specifically the four classes α, β, γ, and ι), we believe that the use of CA inhibitors and activators can open up new therapeutic strategies for many diseases associated with microbial dysbiosis, such as the various gastrointestinal disorders and the same colorectal cancer.

RevDate: 2021-11-21

Ciftciler R, AE Ciftciler (2021)

The importance of microbiota in hematology.

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis pii:S1473-0502(21)00320-7 [Epub ahead of print].

Whilst particular infectious bacteria are well-established to be associated with hematological diseases, more recent interest has focused on the entire microbial community of mucosal surfaces. In particular, the link between hematology and the microbiota (defined as the total assemblage of microorganisms in a mucosal environment)/ microbiome (i.e. the entire ecological habitat, including organisms, their genomes and environmental conditions) is becoming more well-known. Dysbiosis, or a change in the microbiome, has been linked to the development of neoplasms, infections, inflammatory illnesses, and immune-mediated disorders, according to growing data. Microbiota may influence distant tumor microenvironment through a variety of methods, including cytokine release control, dendritic cell activation, and T-cell lymphocyte stimulation. There are numerous major implications to study the microbiome in patients with benign and malignant hematologic disorders. In this review, we investigated the structure and function of the microbiome in patients with benign and malignant hematological diseases. Chemotherapy and immunosuppressive agents used in treatment of these benign and malignant hematological diseases may cause or exacerbate dysbiosis and infectious problems. After understanding the importance of microbiota in hematological diseases, we think that use of probiotics and dietary prebiotic substances targeting microbiota modification aiming to improve hematological disease outcomes should be investigated in future studies.

RevDate: 2021-11-19

Han T, Hu X, Li K, et al (2021)

Bifidobacterium infantis Maintains Genome Stability in Ulcerative Colitis via Regulating Anaphase-Promoting Complex Subunit 7.

Frontiers in microbiology, 12:761113.

Probiotics represents a promising intestinal microbiota-targeted therapeutic method for the treatment of ulcerative colitis (UC). Several lines of evidence implicate that Bifidobacterium infantis serves as a probiotic strain with proven efficacy in maintaining the remission of UC. However, the exact mechanisms underlying the beneficial effects of B. infantis on UC progression have yet to be elucidated. Herein, we provide evidence that B. infantis acts as a key predisposing factor for the maintenance of host genome stability. First, we showed that the fecal microbiota transplantation (FMT) of UC-derived feces contributes to more severely DNA damage in dextran sodium sulfate (DSS)-induced mice likely due to mucosa-associated microbiota alterations, as reflected by the rapid appearance of DNA double strand breaks (DSBs), a typical marker of genome instability. Genomic DNA damage analysis of colon tissues derived from healthy controls, patients with UC or dysplasia, and colitis associated cancer (CAC) patients, revealed an enhanced level of DSBs with aggravation in the degree of the intestinal mucosal lesions. To evaluate whether B. infantis modulates the host genome stability, we employed the DSS-induced colitis model and a TNFα-induced intestinal epithelial cell model. Following the administration of C57BL/6 mice with B. infantis via oral gavage, we found that the development of DSS-induced colitis in mice was significantly alleviated, in contrast to the colitis model group. Notably, B. infantis administration decreased DSB levels in both DSS-induced colitis and TNF-treated colonial cell model. Accordingly, our bioinformatic and functional studies demonstrated that B. infantis altered signal pathways involved in ubiquitin-mediated proteolysis, transcriptional misregulation in cancer, and the bacterial invasion of epithelial cells. Mechanistically, B. infantis upregulated anaphase-promoting complex subunit 7 (APC7), which was significantly suppressed in colitis condition, to activate the DNA repair pathway and alter the genome stability, while downregulation of APC7 abolished the efficiency of B. infantis treatment to induce a decrease in the level of DSBs in TNFα-induced colonial cells. Collectively, our results support that B. infantis orchestrates a molecular network involving in APC7 and genome stability, to control UC development at the clinical, biological, and mechanistic levels. Supplying B. infantis and targeting its associated pathway will yield valuable insight into the clinical management of UC patients.

RevDate: 2021-11-19

Vandeputte D, De Commer L, Tito RY, et al (2021)

Temporal variability in quantitative human gut microbiome profiles and implications for clinical research.

Nature communications, 12(1):6740.

While clinical gut microbiota research is ever-expanding, extending reference knowledge of healthy between- and within-subject gut microbiota variation and its drivers remains essential; in particular, temporal variability is under-explored, and a comparison with cross-sectional variation is missing. Here, we perform daily quantitative microbiome profiling on 713 fecal samples from 20 Belgian women over six weeks, combined with extensive anthropometric measurements, blood panels, dietary data, and stool characteristics. We show substantial temporal variation for most major gut genera; we find that for 78% of microbial genera, day-to-day absolute abundance variation is substantially larger within than between individuals, with up to 100-fold shifts over the study period. Diversity, and especially evenness indicators also fluctuate substantially. Relative abundance profiles show similar but less pronounced temporal variation. Stool moisture, and to a lesser extent diet, are the only significant host covariates of temporal microbiota variation, while menstrual cycle parameters did not show significant effects. We find that the dysbiotic Bact2 enterotype shows increased between- and within-subject compositional variability. Our results suggest that to increase diagnostic as well as target discovery power, studies could adopt a repeated measurement design and/or focus analysis on community-wide microbiome descriptors and indices.

RevDate: 2021-11-18

Bernard R, Hourigan SK, MR Nicholson (2021)

Fecal Microbiota Transplantation and Microbial Therapeutics for the Treatment of Clostridioides difficile Infection in Pediatric Patients.

Journal of the Pediatric Infectious Diseases Society, 10(Supplement_3):S58-S63.

Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and has high rates of recurrent disease. As a disease associated with intestinal dysbiosis, gastrointestinal microbiome manipulation and fecal microbiota transplantation (FMT) have evolved as effective, although relatively unregulated therapeutics and not without safety concerns. FMT for the treatment of CDI has been well studied in adults with increasing data reported in children. In this review, we discuss the current body of literature on the use of FMT in children including effectiveness, safety, risk factors for a failed FMT, and the role of FMT in children with comorbidities. We also review emerging microbial therapeutics for the treatment of rCDI.

RevDate: 2021-11-17

Nicholson MR, Alexander E, Ballal S, et al (2021)

Efficacy and Outcomes of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease.

Journal of Crohn's & colitis pii:6425925 [Epub ahead of print].

BACKGROUND: Children with inflammatory bowel disease (IBD) are disproportionally affected by recurrent Clostridioides difficile infection (rCDI). Although fecal microbiota transplantation (FMT) has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in pediatric IBD.

METHODS: We performed a retrospective review of FMT at 20 pediatric centers in the United States (US) from March 2012-March 2020. Children with and without IBD were compared to determine differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared to determine predictors of success. Safety data and IBD-specific outcomes were obtained.

RESULTS: A total of 396 pediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort (76% vs 81%, P=0.17). Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool (P=0.03), were without diarrhea prior to FMT (P=0.03), or had a shorter time from rCDI diagnosis until FMT (P=0.04). Children with a failed FMT were more likely to have clinically active IBD post-FMT (P=0.002) and 19 (13%) patients had an IBD-related hospitalization in the 3 month follow-up.

CONCLUSIONS: Based on the findings from this large US multi-center cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.

RevDate: 2021-11-17

Zhao Z, Ning J, Bao XQ, et al (2021)

Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis.

Microbiome, 9(1):226.

BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in PD pathogenesis, known as the microbiota-gut-brain axis. As an approach to re-establishing a normal microbiota community, fecal microbiota transplantation (FMT) has exerted beneficial effects on PD in recent studies. Here, in this study, we established a chronic rotenone-induced PD mouse model to evaluate the protective effects of FMT treatment on PD and to explore the underlying mechanisms, which also proves the involvement of gut microbiota dysbiosis in PD pathogenesis via the microbiota-gut-brain axis.

RESULTS: We demonstrated that gut microbiota dysbiosis induced by rotenone administration caused gastrointestinal function impairment and poor behavioral performances in the PD mice. Moreover, 16S RNA sequencing identified the increase of bacterial genera Akkermansia and Desulfovibrio in fecal samples of rotenone-induced mice. By contrast, FMT treatment remarkably restored the gut microbial community, thus ameliorating the gastrointestinal dysfunctions and the motor deficits of the PD mice. Further experiments revealed that FMT administration alleviated intestinal inflammation and barrier destruction, thus reducing the levels of systemic inflammation. Subsequently, FMT treatment attenuated blood-brain barrier (BBB) impairment and suppressed neuroinflammation in the substantia nigra (SN), which further decreased the damage of dopaminergic neurons. Additional mechanistic investigation discovered that FMT treatment reduced lipopolysaccharide (LPS) levels in the colon, the serum, and the SN, thereafter suppressing the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products both in the SN and the colon.

CONCLUSIONS: Our current study demonstrates that FMT treatment can correct the gut microbiota dysbiosis and ameliorate the rotenone-induced PD mouse model, in which suppression of the inflammation mediated by the LPS-TLR4 signaling pathway both in the gut and the brain possibly plays a significant role. Further, we prove that rotenone-induced microbiota dysbiosis is involved in the genesis of PD via the microbiota-gut-brain axis. Video abstract.

RevDate: 2021-11-17
CmpDate: 2021-11-17

Fremin BJ, Nicolaou C, AS Bhatt (2021)

Simultaneous ribosome profiling of hundreds of microbes from the human microbiome.

Nature protocols, 16(10):4676-4691.

Ribosome profiling enables sequencing of ribosome-bound fragments of RNA, revealing which transcripts are being translated as well as the position of ribosomes along mRNAs. Although ribosome profiling has been applied to cultured bacterial isolates, its application to uncultured, mixed communities has been challenging. We present MetaRibo-Seq, a protocol that enables the application of ribosome profiling directly to the human fecal microbiome. MetaRibo-Seq is a benchmarked method that includes several modifications to existing ribosome profiling protocols, specifically addressing challenges involving fecal sample storage, purity and input requirements. We also provide a computational workflow to quality control and trim reads, de novo assemble a reference metagenome with metagenomic reads, align MetaRibo-Seq reads to the reference, and assess MetaRibo-Seq library quality (https://github.com/bhattlab/bhattlab_workflows/tree/master/metariboseq). This MetaRibo-Seq protocol enables researchers in standard molecular biology laboratories to study translation in the fecal microbiome in ~5 d.

RevDate: 2021-11-16

Wu J, Qiu M, Zhang C, et al (2021)

Type 3 resistant starch from Canna edulis modulates obesity and obesity-related low-grade systemic inflammation in mice by regulating gut microbiota composition and metabolism.

Food & function [Epub ahead of print].

Obesity is a most prevalent human health problem. Several studies showed that appropriate modulation of gut microbiota could help reshape the metabolic profile of obese individuals, thereby altering the development of obesity. A nutritional strategy for treating obesity includes prebiotics. Type 3 Resistant Starch from Canna edulis (Ce-RS3) is a dietary fiber that exerts potential effects on the intestinal microbial community; however, the metabolic landscape and anti-obesity mechanism remain unclear. In the present study, obese mice were treated with Ce-RS3, and 16S rRNA gene sequencing and metabolomics were used to measure changes in gut microbiota and fecal metabolic profiles, respectively. At the end of the treatment (13 weeks), we observed slow weight gain in the mice, and pathological damage and inflammation were substantially reduced. Ce-RS3 constructs a healthy gut microbiota structure and can enhance intestinal immunity and reduce metabolic inflammation. Ce-RS3 increased the diversity of gut microbiota with enrichment of Bifidobacterium and Roseburia. Ce-RS3 regulated the systemic metabolic dysbiosis in obese mice and adjusted 26 abnormal metabolites in amino acids and lipids metabolism, many of which are related to the microbiome. More importantly, we found that the anti-obesity effect of Ce-RS3 can be transferred by fecal transplantation. The beneficial effects of Ce-RS3 might derive from gut microbiota changes, which might improve obesity and metabolic inflammation by altering host-microbiota interactions with impacts on the metabolome. In conclusion, Ce-RS3 can be used as a prebiotic with potential value for the treatment of obesity.

RevDate: 2021-11-15

Sivaraj S, Copeland JK, Malik A, et al (2021)

Characterization and predictive functional profiles on metagenomic 16S rRNA data of liver transplant recipients: A longitudinal study.

Clinical transplantation [Epub ahead of print].

Long-term survival after Liver Transplantation (LT) is often compromised by infectious and metabolic complications. We aimed to delineate alterations in intestinal microbiome (IM) over time that could contribute to medical complications compromising long-term survival following LT. Fecal samples from LT recipients were collected at 3 months (3M) and 6 months (6M) post-LT. The bacterial DNA was extracted using E.Z.N.A.® Stool DNA Kit and 16S rRNA gene sequencing at V4 hypervariable region was performed. DADA2 and Phyloseq was implemented to analyze the taxonomic composition. Differentially abundant taxa were identified by metagenomeSeq and LEfSe. Piphillin, an Inferred functional metagenomic analysis tool was used to study the bacterial functional content. For comparison, healthy samples were extracted from NCBI and analyzed similarly. The taxonomic & functional profiles of LT recipients were validated with metagenomic sequencing data from animals exposed to immunosuppressants using Venny. Our findings provide a new perspective on longitudinal increase in specific IM communities post-LT along with an increase in bacterial genes associated with metabolic and infectious disease. This article is protected by copyright. All rights reserved.

RevDate: 2021-11-15

Chen CC, CH Chiu (2021)

Current and future applications of fecal microbiota transplantation for children.

Biomedical journal pii:S2319-4170(21)00153-0 [Epub ahead of print].

Fecal microbiota transplantation (FMT) is a new and adequate route to modify the microbial ecosystem in gastrointestinal tract of the hosts. Intestinal microbiota is highly associated with human health and disease. According to the reports of human clinical trials or case series, the application of FMT ranged from Clostridiodes difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome, refractory diarrhea, diabetes mellitus, metabolic syndrome, and even neurologic diseases, including Parkinson disease, and neuropsychiatric disorder (autism spectrum disorder, ASD). Although the current allowed indication of FMT is CDI in Taiwan, more application and development are expectable in the future. There is a relative rare data available for children in application of fecal microbiota transplantation. Thus, we review previous published research inspecting FMT in children, and address particular considerations when conducting FMT in pediatric patients.

RevDate: 2021-11-13

Kim ER, Park JS, Kim JH, et al (2021)

A GLP-1/GLP-2 receptor dual agonist to treat non-alcoholic steatohepatitis: targeting the gut-liver axis and microbiome.

Hepatology (Baltimore, Md.) [Epub ahead of print].

Currently there is no FDA-approved drug to treat nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut-liver axis in their pathogenesis, we investigated the therapeutic effect of a long-acting dual agonist of glucagon-like peptide (GLP)-1 and GLP-2 receptors in mice with NAFLD/NASH. C57BL/6J mice were fed a choline-deficient high fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1-Fc, GLP2-Fc, or GLP1/2-Fc subcutaneously every two days for four weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were utilized to evaluate direct peptide effect. Immunohistochemistry, qPCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well-developed NASH phenotypes. GLP1/2-Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, goblet cells of intestine compared to a vehicle group. Similar effects of GLP1/2-Fc were found in in vitro cell systems. GLP1/2-Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) in order to gain further insight into the mechanism of GLP1/2-Fc-mediated protection. We confirmed that FMT exerted an additive effect on GLP1-Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation and hepatic fibrosis. CONCLUSION: A long-acting dual agonist of GLP-1 and GLP-2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.

RevDate: 2021-11-15

Gao T, Wang Z, Dong Y, et al (2021)

Melatonin-Mediated Colonic Microbiota Metabolite Butyrate Prevents Acute Sleep Deprivation-Induced Colitis in Mice.

International journal of molecular sciences, 22(21): pii:ijms222111894.

Radical cure colitis is a severe public health threat worldwide. Our previous studies have confirmed that melatonin can effectively improve gut microbiota disorder and mucosal injury caused by sleep deprivation (SD). The present study further explored the mechanism whereby exogenous melatonin prevented SD-induced colitis. 16S rRNA high-throughput sequencing and metabolomics analysis were used to explore the correlation between SD-induced colitis and intestinal microbiota and metabolite composition in mice. Fecal microbiota transplantation (FMT) and melatonin or butyrate supplementation tests verified the core role of gut microbiota in melatonin-alleviating SD-induced colitis. Further, in vitro tests studied the modulatory mechanism of metabolite butyrate. The results demonstrated that SD leads to reductions in plasma melatonin levels and colonic Card9 expression and consequent occurrence of colitis and gut microbiota disorder, especially the downregulation of Faecalibacterium and butyrate levels. The FMT from SD-mice to normal mice could restore SD-like colitis, while butyrate supplementation to SD-mice inhibited the occurrence of colitis, but with no change in the plasma melatonin level in both treatments. However, melatonin supplementation reversed all inductions in SD-mice. In intestinal epithelial cells, the inflammatory ameliorative effect of butyrate was blocked with pretreatments of HDAC3 agonist and HIF-1α antagonist but was mimicked by GSK-3β and p-P65 antagonists. Therefore, the administration of MLT may be a better therapy for SD-induced colitis relative to butyrate. A feasible mechanism would involve that melatonin up-regulated the Faecalibacterium population and production of its metabolite butyrate and MCT1 expression and inhibited HDAC3 in the colon, which would allow p-GSK-3β/β-catenin/HIF-1α activation and NF-κB/NLRP3 suppression to up-regulate Card9 expression and suppress inflammation response.

RevDate: 2021-11-15

Chen Z, Wang B, Dong J, et al (2021)

Gut Microbiota-Derived l-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury.

International journal of molecular sciences, 22(21): pii:ijms222111436.

Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived l-Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of l-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. l-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. l-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of l-Histidine, accumulated in peripheral blood and lung tissues following l-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced l-Histidine and ImP are promising radioprotective agents.

RevDate: 2021-11-15

Popov J, Caputi V, Nandeesha N, et al (2021)

Microbiota-Immune Interactions in Ulcerative Colitis and Colitis Associated Cancer and Emerging Microbiota-Based Therapies.

International journal of molecular sciences, 22(21): pii:ijms222111365.

Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn's disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.

RevDate: 2021-11-13

Zhou H, Yuan Y, Wang H, et al (2021)

Gut Microbiota: A Potential Target for Cancer Interventions.

Cancer management and research, 13:8281-8296.

The gut microbiota plays a crucial role in many physiological processes in the human body. Dysbiosis can disrupt the intestinal barrier and alter metabolism and immune responses, leading to the development of diseases. Over the past few decades, evidence has accumulated linking changes in the composition of the gut microbiota to dozens of seemingly unrelated conditions, including cancer. Overall, the gut microbiota mainly affects the occurrence and development of cancer by damaging host DNA, forming and maintaining a pro-inflammatory environment, and affecting host immune responses. In addition, the gut microbiota can also affect the efficacy and toxicity of chemotherapy, radiotherapy, and immunotherapy. Scientists attempt to improve the efficacy and decrease the toxicity of these treatment modalities by fine-tuning the gut microbiota. The aim of this review is to assist researchers and clinicians in developing new strategies for the detection and treatment of tumors by providing the latest information on the intestinal microbiome and cancer, as well as exploring potential application prospects and mechanisms of action.

RevDate: 2021-11-11

Hou K, Zhang S, Wu Z, et al (2021)

Reconstruction of intestinal microecology of Type 2 diabetes by fecal microbiota transplantation: Why and how.

Bosnian journal of basic medical sciences [Epub ahead of print].

Type 2 diabetes (T2D) is a chronic metabolic disease characterized by hyperglycemia due to insulin resistance. Mounting evidence has correlated T2D to alterations in the composition of gut microbiota. Accordingly, targeting the gut microbiota has become an emerging strategy for T2D management. The aim of this article is to get a better insight into the rationale for targeting gut microbiota in T2D treatment. Thus, we herein reviewed the change of gut microbiota composition in T2D, factors shaping gut microbiota, and potential mechanisms behind the contribution of gut microbiota to T2D pathogenesis. At present, it has become possible to use intestinal microorganism capsules, bacteria liquid, and other preparations to carry out fecal microbiota transplantation for the treatment and intervention of T2D with insulin resistance and immune-mediated Type 1 diabetes (T1D).

RevDate: 2021-11-12

Pan P, Atkinson SN, Taylor B, et al (2021)

Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice.

Frontiers in immunology, 12:749002.

Graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). An impaired intestinal epithelial barrier is an important component of GVHD pathogenesis. However, contributing host factors that modulate mucosal barrier integrity during GVHD are poorly defined. We hypothesized that vitamin A and retinoic acid (RA) exert positive impacts on maintaining intestinal barrier function after HSCT, thus preventing or dampening GVHD severity. Unexpectedly, we found that exogenous RA increased intestinal permeability of recipient mice after allogeneic HSCT. Serum bacterial endotoxin levels were significantly higher in GVHD mice fed a vitamin A-high (VAH) diet compared to those fed a vitamin A-normal (VAN) diet, indicating a more compromised intestinal barrier function. Furthermore, VAH mice showed more severe lung GVHD with increased donor T cell infiltration in this tissue and died significantly faster than VAN recipients. 16S rRNA sequencing of fecal samples revealed significant differences in the diversity and composition of gut microbiota between VAN and VAH transplant recipients. Collectively, we show that retinoic acid signaling may negatively impact intestinal barrier function during GVHD. Mild vitamin A supplementation is associated with increased lung GVHD and more profound gut dysbiosis. Micronutrients such as vitamin A could modulate complications of allogeneic HSCT, which may be mediated by shaping gut microbiota.

RevDate: 2021-11-12
CmpDate: 2021-11-12

Quraishi MN, Iqbal TH, AL Hart (2021)

Precision Medicine with FMT for Ulcerative Colitis: Are We There Yet?.

Journal of Crohn's & colitis, 15(4):519-520.

RevDate: 2021-11-10

Baldi S, Mundula T, Nannini G, et al (2021)

Microbiota shaping - the effects of probiotics, prebiotics, and fecal microbiota transplant on cognitive functions: A systematic review.

World journal of gastroenterology, 27(39):6715-6732.

BACKGROUND: Dementia is a chronic progressive neurological disease affecting millions of people worldwide, and represents a relevant economic burden for healthcare systems. Although its pathogenesis is still unknown, recent findings have reported that a dysregulated gut-brain axis communication, a fundamental relationship mediated by several host and microbial molecules, is associated with cognitive disorders. In addition, gut microbiota manipulation reduces neuroinflammation, improving cognitive function by restoring the functional gut-brain axis.

AIM: To better define the effects of probiotics, prebiotics, synbiotics, and fecal microbiota transplant (FMT) on cognitive function.

METHODS: We performed a literature search of human randomized clinical trials to examine the effects of the administration of probiotics, prebiotics, synbiotics, or FMT on cognition outcomes in healthy or sick people of every age, sex, and nationality. We systematically searched Embase, Medline/PubMed, Cochrane Library, central and clinicaltrials.gov databases with a combination of comprehensive terms related to cognition and gut microbiota manipulation. Then we carefully reviewed and synthesized the data by type of study design and setting, characteristics of the studied population, kind of intervention (strain type or mixture type, dosage, and frequency of administration), control treatment, inclusion and exclusion criteria, follow-up duration, and cognitive or memory outcomes.

RESULTS: After examining the titles and abstracts, the initial literature screening identified 995 articles, but we added 23 papers in our systematic review. The analyses of these selected studies highlighted that both probiotic supplementation and FMT improved cognitive function regardless of the type and posology of administration and the adopted cognitive tests and questionnaires. We found that most of the studies conducted in healthy people showed a significant positive effect of the intervention on at least one of the performed cognitive tests. Regarding unhealthy subjects, while FMT and especially probiotic administration had multiple beneficial effects on different cognitive functions, supplementation with prebiotics did not provide any cognitive improvement.

CONCLUSION: Probiotic supplementation and FMT may represent a promising strategy to restore gut eubiosis and enhance the cognitive functions of healthy people and patients with neurological disorders.

RevDate: 2021-11-10
CmpDate: 2021-11-10

Fillon M (2021)

Fecal microbiota transplants may aid melanoma immunotherapy resistance.

CA: a cancer journal for clinicians, 71(4):285-286.

RevDate: 2021-11-10
CmpDate: 2021-11-10

Öhman L, Lasson A, Strömbeck A, et al (2021)

Fecal microbiota dynamics during disease activity and remission in newly diagnosed and established ulcerative colitis.

Scientific reports, 11(1):8641.

Patients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2-6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3-10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.

RevDate: 2021-11-09

Zhang S, Chen Q, Kelly CR, et al (2021)

Donor screening for fecal microbiota transplantation in China: Evaluation of 8,483 candidates.

Gastroenterology pii:S0016-5085(21)03726-4 [Epub ahead of print].

RevDate: 2021-11-09

Urbonas T, Ianiro G, Gedgaudas R, et al (2021)

Fecal Microbiome Transplantation for Recurrent Clostridioides difficile Infection: Treatment Efficacy, Short and Long-term Follow-up Results from Consecutive Case Series.

Journal of gastrointestinal and liver diseases : JGLD [Epub ahead of print].

BACKGROUND AND AIMS: Many studies have shown a high effectiveness of fecal microbiota transplantation (FMT) in treatment of recurrent or refractory Clostridioides difficile infection (CDI). Nevertheless, data on long term outcomes and complications after FMT are still lacking. We aimed to evaluate the efficacy, the peri- procedural safety profile and the long-term efficacy and safety of FMT for recurrent CDI during a median follow up period of 24 months.

METHODS: Our study included 60 consecutive patients that were treated from 2015 to 2019 for recurrent CDI. In all patients FMT was performed through the nasoenteric tube placed during gastroscopy. Fresh donor feces were used for FMT from unrelated donors. Pre-FMT preparation included CDI treatment with oral vancomycin 500 mg q.i.d. for at least five days and proton pump inhibitor (PPI) administration before FMT. Follow up data included information about recurrent CDI episodes, early and late complications, health status at 3, 12 and 24 months after FMT.

RESULTS: FMT was performed for 60 patients (median age 72.5 years) with recurrent CDI. Clinical improvement after the first FMT procedure was observed in 48 patients (80%). Ten of 12 initially non-responding patients had a clinical resolution after a second FMT leading to an increased overall cure rate of 96.7 %. The remaining two patients needed a third FMT with a final overall cure rate of 100%. Nine of 60 patients were under immunosuppressive therapy. Six immunosuppressed patients were in the group of initial responders and the remaining three in the initially non-responder group. We observed a very low rate of adverse events in the short and long-term after FMT. During the first eight weeks after the FMT procedure, the death of three patients occurred, but they were not related to the FMT procedure. Patients were followed up for a median of 20 months, with the range from 12 to 55 months. During the follow-up period no long-term serious adverse events (SAE) were documented.

CONCLUSIONS: Our study confirms excellent efficacy rates of FMT in the treatment of recurrent CDI. In addition, this study shows that it is possible to avoid short term SAE when FMT is administered via a nasoenteric tube by following a very stringent peri-procedural patient follow-up protocol. Our study also demonstrates good safety with a low rate of long-term adverse events after FMT.

RevDate: 2021-11-09

Zhou F, Li YL, Zhang X, et al (2021)

Polyphenols from Fu Brick Tea Reduce Obesity via Modulation of Gut Microbiota and Gut Microbiota-Related Intestinal Oxidative Stress and Barrier Function.

Journal of agricultural and food chemistry [Epub ahead of print].

Fu brick tea (FBT) is a microbial-fermented tea, which is produced by the solid-state fermentation of tea leaves. Previous studies have proved that FBT aqueous extracts could attenuate obesity and gut microbiota dysbiosis. However, the bioactive components in FBT that contribute to these activities remain unclear. In this study, we aimed to investigate the effects of FBT polyphenols (FBTPs) on obesity, gut microbiota, and gut microbiota-related intestinal oxidative stress and barrier function and to further investigate whether the antiobesity effect of FBTPs was dependent on the alteration of gut microbiota. The results showed that FBTP supplementation effectively attenuated obesity in high-fat diet (HFD)-fed rats. FBTP supplementation improved the intestinal oxidative stress and intestinal barrier function, including intestinal inflammation and the integrity of the intestinal barrier. Furthermore, FBTP intervention significantly attenuated HFD-induced gut microbiota dysbiosis, characterized by increased phylogenetic diversity and decreased Firmicutes/Bacteroidetes ratio. Certain core microbes, including Akkermansia muciniphila, Alloprevotella, Bacteroides, and Faecalibaculum, were also found to be improved by FBTPs. Moreover, the antiobesity effect of FBTPs was gut microbiota-dependent, as demonstrated by a fecal microbiota transplantation experiment. Collectively, we concluded that FBTPs reduced obesity by modulating the gut microbiota and gut microbiota-related intestinal oxidative stress and barrier function. Therefore, FBTPs may be used as prebiotic agents to treat obesity and gut microbiota dysbiosis in obese individuals.

RevDate: 2021-11-09

Dai C, WX Liu (2021)

Refractory Immune Checkpoint Inhibitor-induced Colitis Improved by Fecal Microbiota Transplantation: A Case Report.

Inflammatory bowel diseases pii:6424075 [Epub ahead of print].

RevDate: 2021-11-09

Berding K, JF Cryan (2021)

Microbiota-targeted interventions for mental health.

Current opinion in psychiatry pii:00001504-900000000-99004 [Epub ahead of print].

PURPOSE OF REVIEW: The gut microbiota has emerged as a key conduit in mental health and is a promising target for interventions. This review provides an update on recent advances in using microbiota-targeted approaches for the management of mental health.

RECENT FINDINGS: Approaches that have emerged as microbiota-targeted interventions in the management of mental health include probiotics, prebiotics, synbiotics, fecal microbiota transplant as well as diet. Among these approaches, probiotic supplementation has been investigated most prominently, providing promising evidence for its use in improving mood and anxiety. There is also growing interest in the use of multistrain probiotics, whole dietary interventions or combined approaches, with encouraging results emerging from recent studies.

SUMMARY: Although the current literature preliminarily supports targeting the microbiota to manage mental health and use as adjuvant therapies for certain brain disorders, large gaps remain and especially data including clinical cohorts remains scarce. Research studies including larger cohorts, well-characterized clinical populations and defined duration and dosage of the intervention are required to develop evidence-based guidelines for microbiota-targeted strategies.

RevDate: 2021-11-08

van der Vossen EWJ, Bastos D, Stols-Gonçalves D, et al (2021)

Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome.

Gut microbes, 13(1):1993513.

Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the pathophysiology of insulin resistance. Despite these developments, there is still a limited understanding of the multitude of effects associated with FMT on the general physiology of the host, beyond changes in gut microbiome composition. We examined the effect of either allogenic (lean donor) or autologous FMTs on the gut microbiome, plasma metabolome, and epigenomic (DNA methylation) reprogramming in peripheral blood mononuclear cells in individuals with metabolic syndrome measured at baseline (pre-FMT) and after 6 weeks (post-FMT). Insulin sensitivity was determined with a stable isotope-based 2 step hyperinsulinemic clamp and multivariate machine learning methodology was used to uncover discriminative microbes, metabolites, and DNA methylation loci. A larger gut microbiota shift was associated with an allogenic than with autologous FMT. Furthemore, the data results of the the allogenic FMT group data indicates that the introduction of new species can potentially modulate the plasma metabolome and (as a result) the epigenome. Most notably, the introduction of Prevotella ASVs directly correlated with methylation of AFAP1, a gene involved in mitochondrial function, insulin sensitivity, and peripheral insulin resistance (Rd, rate of glucose disappearance). FMT was found to have notable effects on the gut microbiome but also on the host plasma metabolome and the epigenome of immune cells providing new avenues of inquiry in the context of metabolic syndrome treatment for the manipulation of host physiology to achieve improved insulin sensitivity.

RevDate: 2021-11-08

Yang B, Tian H, Ye C, et al (2021)

The Efficacy and Safety of Fecal Microbiota Transplantation Combined With Biofeedback for Mixed Constipation: A Retrospective Cohort Study.

Frontiers in medicine, 8:746990.

This study aims to assess the effectiveness and safety of fecal microbiota transplantation (FMT) combined with biofeedback for patients with mixed constipation. Patients who received biofeedback (biofeedback group, n = 40) and those who received FMT combined with biofeedback (FMT combination group, n = 45) were enrolled. Spontaneous bowel movements (SBMs) frequency, Bristol Stool Form Scale (BSFS), and Patient Assessment of Constipation Symptoms (PAC-SYM) score were analyzed to evaluate the effect of treatment. Gastrointestinal Quality of Life Index (GIQLI) scores of patients were used to assess the quality of life, and the safety of FMT combination therapy was evaluated by the presence of adverse events. The 16S rRNA gene sequencing was performed on the fecal samples of 12 donors, feces of 31 patients before and after receiving FMT combination treatment. Comparing the biofeedback group and the FMT combination group 1 month after the treatment, significant differences were observed in the mean value of SBM frequency, BSFS, and PAC-SYM scores, which were 2.15 ± 1.05 vs. 3.61 ± 0.89 (p = 0.0031), 2.1 ± 0.9 vs. 2.5 ± 1.2 (p = 0.008), and 2.4 ± 0.5 vs. 2.2 ± 0.6 (p = 0.0021), respectively. Meanwhile, FMT combination therapy had long-term beneficial effects according to the data collected at six months and 12 months after the treatment. With respect to the quality of life, GIQLI scores were higher in the FMT combination group (103.6 ± 15.1) compared with that in the biofeedback group (88.7 ± 10.1) one month after administration (p = 0.0042). In addition, there were no significant differences between the two groups in adverse events, including abdominal pain, diarrhea, dizziness, nausea, vomiting, and other side effects. Results of 16S rRNA gene sequencing showing some well-known probiotics had significantly increased after FMT combination treatment compared with pre-FMT samples, such as Prevotella and Bifidobacterium. Findings of this study suggested that FMT combined with biofeedback could be effective and safe for patients with mixed constipation.

RevDate: 2021-11-08

Xiang L, Yu Y, Ding X, et al (2021)

Exclusive Enteral Nutrition Plus Immediate vs. Delayed Washed Microbiota Transplantation in Crohn's Disease With Malnutrition: A Randomized Pilot Study.

Frontiers in medicine, 8:666062.

Background: The potential of washed microbiota transplantation (WMT) in Crohn's disease (CD) has been reported. This study aimed to explore the suitable timing of WMT in patients with CD complicated with malnutrition. Methods: This is a randomized, open-label study. Patients with active CD complicated with malnutrition were included and 1:1 randomized to undergo WMT at day 1 (group WMT-DAY1) or day 8 (group WMT-DAY8). The observation duration was 15 days. Exclusive enteral nutrition (EEN) was administered in both groups. The primary outcome was the improvement in nutritional parameters at day 8 and day 15 in two groups. The secondary outcome was the rate of clinical remission at day 15 in two groups. Results: Totally 19 patients completed the trial. At day 8, the lymphocyte count, albumin and prealbumin increased significantly compared to those at day 1 in group WMT-DAY1 (p = 0.018, p = 0.028, p = 0.028, respectively), while no significant increase in any nutritional parameter was shown in group WMT-DAY8. At day 15, albumin increased significantly compared to that at day 1 in both groups (p < 0.05), while significant increase in prealbumin was only shown in group WMT-DAY1 (p = 0.004) compared to that at day 1. The rate of clinical remission at day 15 in group WMT-DAY1 and group WMT-DAY8 was 87.5% (7/8) and 72.7% (8/11), respectively (p = 0.603). Conclusion: EEN combined with immediate WMT intervention could rapidly improve the nutritional status and induce clinical remission in malnourished patients with CD. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02897661.

RevDate: 2021-11-08

Liu J, Gu L, Zhang M, et al (2021)

The Fecal Microbiota Transplantation: A Remarkable Clinical Therapy for Slow Transit Constipation in Future.

Frontiers in cellular and infection microbiology, 11:732474.

Slow transit constipation is a common condition that would be difficult to treat in clinical practice with a widespread incidence in the population. Pharmacotherapy and surgery are common treatment modalities. However, the clinical effect is limited, and patients still suffer from it. As the researchers strived in this field for decades, the profound relationship between slow transit constipation and fecal microbiota transplantation has comprehensively been sustained. It is very pivotal to maintain intestinal homeostasis, the structure function and metabolic function of symbiotic bacteria, which can inhibit the engraftment of intestinal pathogens. This mini review explains the treatment effects and possible mechanisms of the fecal microbiota transplantation in treating slow transit constipation. Simultaneously, it is found that there is significant improvement in the disease by adjusting the intestinal microbes like fecal microbiota transplantation. Fecal microbiota transplantation has efficient therapeutic effects in slow transit constipation compared with traditional therapies.

RevDate: 2021-11-08

Alexander T, Snowden JA, Burman J, et al (2021)

Intestinal Microbiome in Hematopoietic Stem Cell Transplantation For Autoimmune Diseases: Considerations and Perspectives on Behalf of Autoimmune Diseases Working Party (ADWP) of the EBMT.

Frontiers in oncology, 11:722436.

Over the past decades, hematopoietic stem cell transplantation (HSCT) has been evolving as specific treatment for patients with severe and refractory autoimmune diseases (ADs), where mechanistic studies have provided evidence for a profound immune renewal facilitating the observed beneficial responses. The intestinal microbiome plays an important role in host physiology including shaping the immune repertoire. The relationships between intestinal microbiota composition and outcomes after HSCT for hematologic diseases have been identified, particularly for predicting the mortality from infectious and non-infectious causes. Furthermore, therapeutic manipulations of the gut microbiota, such as fecal microbiota transplant (FMT), have emerged as promising therapeutic approaches for restoring the functional and anatomical integrity of the intestinal microbiota post-transplantation. Although changes in the intestinal microbiome have been linked to various ADs, studies investigating the effect of intestinal dysbiosis on HSCT outcomes for ADs are scarce and require further attention. Herein, we describe some of the landmark microbiome studies in HSCT recipients and patients with chronic ADs, and discuss the challenges and opportunities of microbiome research for diagnostic and therapeutic purposes in the context of HSCT for ADs.

RevDate: 2021-11-08

Liu Y, Wang H, Gui S, et al (2021)

Proteomics analysis of the gut-brain axis in a gut microbiota-dysbiosis model of depression.

Translational psychiatry, 11(1):568.

Major depressive disorder (MDD) is a serious mental illness. Increasing evidence from both animal and human studies suggested that the gut microbiota might be involved in the onset of depression via the gut-brain axis. However, the mechanism in depression remains unclear. To explore the protein changes of the gut-brain axis modulated by gut microbiota, germ-free mice were transplanted with gut microbiota from MDD patients to induce depression-like behaviors. Behavioral tests were performed following fecal microbiota transplantation. A quantitative proteomics approach was used to examine changes in protein expression in the prefrontal cortex (PFC), liver, cecum, and serum. Then differential protein analysis and weighted gene coexpression network analysis were used to identify microbiota-related protein modules. Our results suggested that gut microbiota induced the alteration of protein expression levels in multiple tissues of the gut-brain axis in mice with depression-like phenotype, and these changes of the PFC and liver were model specific compared to chronic stress models. Gene ontology enrichment analysis revealed that the protein changes of the gut-brain axis were involved in a variety of biological functions, including metabolic process and inflammatory response, in which energy metabolism is the core change of the protein network. Our data provide clues for future studies in the gut-brain axis on protein level and deepen the understanding of how gut microbiota cause depression-like behaviors.

RevDate: 2021-11-08

Bajaj JS, Shamsaddini A, Acharya C, et al (2021)

Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis.

Gut microbes, 13(1):1993584.

BACKGROUND & AIMS: Altered gut microbiota is associated with poor outcomes in cirrhosis, including infections and hepatic encephalopathy (HE). However, the role of bacterial virulence factors (VFs) is unclear. Aim: Define association of VFs with cirrhosis severity and infections, their linkage with outcomes, and impact of fecal microbiota transplant (FMT).

METHODS: VF abundances were determined using metagenomic analysis in stools from controls and cirrhosis patients (compensated, HE-only, ascites-only, both and infected). Patients were followed for 90-day hospitalizations and 1-year death. Stool samples collected before/after a placebo-controlled FMT trial were also analyzed. Bacterial species and VFs for all species and selected pathogens (Escherichia, Klebsiella, Pseudomonas, Staphylococcus, Streptococcus, and Enterococcus spp) were compared between groups. Multi-variable analyses were performed for clinical biomarkers and VFs for outcome prediction. Changes in VFs pre/post-FMT and post-FMT/placebo were analyzed. Results: We included 233 subjects (40 controls, 43 compensated, 30 HE-only, 20 ascites-only, 70 both, and 30 infected). Decompensated patients, especially those with infections, had higher VFs coding for siderophores, biofilms, and adhesion factors versus the rest. Biofilm and adhesion VFs from Enterobacteriaceae and Enterococcus spp associated with death and hospitalizations independent of clinical factors regardless of when all VFs or selected pathogens were analyzed. FMT was associated with reduced VF post-FMT versus pre-FMT and post-placebo groups.

CONCLUSIONS: Virulence factors from multiple species focused on adhesion and biofilms increased with decompensation and infections, associated with death and hospitalizations independent of clinical factors, and were attenuated with FMT. Strategies focused on targeting multiple virulence factors could potentially impact outcomes in cirrhosis.

PRESENTATIONS: Portions of this manuscript were an oral presentation in the virtual International Liver Congress 2021.

ABBREVIATIONS: VF: virulence factors, HE: hepatic encephalopathy, FMT: Fecal microbiota transplant, PPI: proton pump inhibitors, LPS: lipopolysaccharides, VFDB: Virulence factor database, OTU: operational taxonomic units, SBP: spontaneous bacterial peritonitis, UTI: urinary tract infections, MRSA: methicillin resistant Staphylococcus aureus, VRE: vancomycin-resistant Enterococcus, MAAsLin2: Microbiome Multivariable Associations with Linear Models, LPS: lipopolysaccharides, AKI: acute kidney injury.

RevDate: 2021-11-05

Li N, Chen H, Cheng Y, et al (2021)

Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study.

Frontiers in cellular and infection microbiology, 11:759435.

Autism spectrum disorder (ASD) is a severe brain development disorder that is characterized by deficits in social communication and restricted, repetitive and stereotyped behaviors. Accumulating evidence has suggested that gut microbiota disorders play important roles in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients. Manipulation of the gut microbiota by fecal microbiota transplantation (FMT) was recently shown to be a promising therapy for the treatment of various diseases. Here, we performed a clinical trial to evaluate the effect of FMT on gastrointestinal (GI) and ASD symptoms and gut microbiota alterations in children with ASD. We found that there was a large difference in baseline characteristics of behavior, GI symptoms, and gut microbiota between children with ASD and typically developing (TD) control children. FMT could improve GI symptoms and ASD symptoms without inducing any severe complications. Similarly, FMT significantly changed the serum levels of neurotransmitters. We further observed that FMT could promote the colonization of donor microbes and shift the bacterial community of children with ASD toward that of TD controls. The abundance of Eubacterium coprostanoligenes pre-FMT was positively correlated with high GSRS scores, whereas a decrease in Eubacterium coprostanoligenes abundance induced by FMT was associated with the FMT response. Our data suggest that FMT might be a promising therapeutic strategy to improve the GI and behavioral symptoms of patients with ASD, possibly due to its ability to alter gut microbiota and highlight a specific microbiota intervention that targets Eubacterium coprostanoligenes that can enhance the FMT response. This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (trial registration number ChiCTR1800014745).

RevDate: 2021-11-05

Genton L, Lazarevic V, Stojanovic O, et al (2021)

Metataxonomic and Metabolic Impact of Fecal Microbiota Transplantation From Patients With Pancreatic Cancer Into Germ-Free Mice: A Pilot Study.

Frontiers in cellular and infection microbiology, 11:752889.

Background: Body weight (BW) loss is prevalent in patients with pancreatic cancer (PC). Gut microbiota affects BW and is known to directly shape the host immune responses and antitumor immunity. This pilot study evaluated the link between gut microbiota, metabolic parameters and inflammatory/immune parameters, through the fecal material transplantation (FMT) of PC patients and healthy volunteers into germ-free (GF) mice.

Methods: We transplanted the feces from five PC patients and five age- and gender-matched healthy volunteers into two GF mice each. Mouse BW and energy intake were measured every 1-5 days, oral glucose on day 21, insulin tolerance on day 26, fecal bacterial taxonomic profile by 16S rRNA gene sequencing on day 5, 10, 15 and 30, and gut-associated lymphoid tissue T cells, plasma cytokines and weights of fat and muscle mass at sacrifice (day 34). Results are presented as mean ± SD. The continuous parameters of mice groups were compared by linear univariate regressions, and their bacterial communities by Principal Coordinates Analysis (PCoA), Bray-Curtis similarity and ANCOM test.

Results: Recipients of feces from PC patients and healthy volunteers had similar BW gain and food intake. Visceral fat was lower in recipients of feces from PC patients than from healthy individuals (0.72 ± 0.17 vs. 0.92 ± 0.14 g; coeff -0.19, 95% CI -0.38, -0.02, p=0.035). The other non-metataxonomic parameters did not differ between groups. In PCoA, microbiota from PC patients clustered apart from those of healthy volunteers and the same pattern was observed in transplanted mice. The proportions of Clostridium bolteae, Clostridium scindens, Clostridium_g24_unclassified and Phascolarctobacterium faecium were higher, while those of Alistipes obesi, Lachnospiraceae PAC000196_s and Coriobacteriaceae_unclassified species were lower in PC patients and in mice transplanted with the feces from these patients.

Conclusion: In this pilot study, FMT from PC patients was associated with a decrease in visceral fat as compared to FMT from healthy individuals. Some of the differences in fecal microbiota between PC and control samples are common to humans and mice. Further research is required to confirm that feces contain elements involved in metabolic and immune alterations.

RevDate: 2021-11-05

Arora T, V Tremaroli (2021)

Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes.

Frontiers in endocrinology, 12:761834.

Metagenomics studies have shown that type 2 diabetes (T2D) is associated with an altered gut microbiota. Whereas different microbiota patterns have been observed in independent human cohorts, reduction of butyrate-producing bacteria has consistently been found in individuals with T2D, as well as in those with prediabetes. Butyrate is produced in the large intestine by microbial fermentations, particularly of dietary fiber, and serves as primary fuel for colonocytes. It also acts as histone deacetylase inhibitor and ligand to G-protein coupled receptors, affecting cellular signaling in target cells, such as enteroendocrine cells. Therefore, butyrate has become an attractive drug target for T2D, and treatment strategies have been devised to increase its intestinal levels, for example by supplementation of butyrate-producing bacteria and dietary fiber, or through fecal microbiota transplant (FMT). In this review, we provide an overview of current literature indicating that these strategies have yielded encouraging results and short-term benefits in humans, but long-term improvements of glycemic control have not been reported so far. Further studies are required to find effective approaches to restore butyrate-producing bacteria and butyrate levels in the human gut, and to investigate their impact on glucose regulation in T2D.

RevDate: 2021-11-04

Waller KMJ, Leong RW, S Paramsothy (2021)

An update on FMT for the treatment of gastrointestinal diseases.

Journal of gastroenterology and hepatology [Epub ahead of print].

Our understanding of the microbiome and its implications for human health and disease continues to develop. Fecal microbiota transplantation (FMT) is now an established treatment for recurrent Clostridioides difficile infection. There is also increasing evidence for the efficacy of FMT in inducing remission for mild-moderate ulcerative colitis. However, for other indications, data for FMT is limited, with randomised controlled trials rare, typically small and often conflicting. Studies are continuing to explore the role of FMT for many other conditions, including Crohn's disease, functional gut disorders, metabolic syndrome, modulating responses to chemotherapy, eradication of multidrug resistant organisms, and the gut-brain axis. In light of safety, logistical and regulatory challenges, there is a move to standardised products including narrow spectrum consortia. However, the mechanisms underpinning FMT remain incompletely understood, including the role of non-bacterial components, which may limit success of novel microbial approaches.

RevDate: 2021-11-04

Suk KT, H Koh (2021)

A New Perspective on Fecal Microbiota Transplantation in Liver Diseases.

Journal of gastroenterology and hepatology [Epub ahead of print].

Chronic liver disease including non-alcoholic fatty liver disease and alcohol-related liver disease is one of the most common diseases worldwide. The gut-liver axis plays an important role in the pathogenesis of liver disease. Small intestinal bacterial overgrowth, dysbiosis, leaky bowel, bacterial translocation, and imbalanced metabolites are related to the progression of chronic liver disease. Recently, novel therapeutic approaches for microbiota-modulation such as personalized diet, probiotics, prebiotics, antibiotics, engineered microbiotas, phage therapy, stomach operation and fecal microbial transplantation (FMT) have been proposed with numerous promising results in the effectiveness and clinical application. Although the evidence is still lacking, FMT, a type of fecal bacteriotherapy, has been known as a candidate for the treatment of liver disease. This review article focuses on the most recent advances in our understanding of FMT in chronic liver disease such as non-alcoholic and alcohol-related liver disease.

RevDate: 2021-11-04

An L, Wirth U, Koch D, et al (2021)

The Role of Gut-Derived Lipopolysaccharides and the Intestinal Barrier in Fatty Liver Diseases.

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract [Epub ahead of print].

BACKGROUND: Hepatosteatosis is the earliest stage in the pathogenesis of nonalcoholic fatty (NAFLD) and alcoholic liver disease (ALD). As NAFLD is affecting 10-24% of the general population and approximately 70% of obese patients, it carries a large economic burden and is becoming a major reason for liver transplantation worldwide. ALD is a major cause of morbidity and mortality causing 50% of liver cirrhosis and 10% of liver cancer related death. Increasing evidence has accumulated that gut-derived factors play a crucial role in the development and progression of chronic liver diseases.

METHODS: A selective literature search was conducted in Medline and PubMed, using the terms "nonalcoholic fatty liver disease," "alcoholic liver disease," "lipopolysaccharide," "gut barrier," and "microbiome."

RESULTS: Gut dysbiosis and gut barrier dysfunction both contribute to chronic liver disease by abnormal regulation of the gut-liver axis. Thereby, gut-derived lipopolysaccharides (LPS) are a key factor in inducing the inflammatory response of liver tissue. The review further underlines that endotoxemia is observed in both NAFLD and ALD patients. LPS plays an important role in conducting liver damage through the LPS-TLR4 signaling pathway. Treatments targeting the gut microbiome and the gut barrier such as fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, and intestinal alkaline phosphatase (IAP) represent potential treatment modalities for NAFLD and ALD.

CONCLUSIONS: The gut-liver axis plays an important role in the development of liver disease. Treatments targeting the gut microbiome and the gut barrier have shown beneficial effects in attenuating liver inflammation and need to be further investigated.

RevDate: 2021-11-04

Zhang W, An Y, Qin X, et al (2021)

Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges.

Frontiers in oncology, 11:739648.

Accumulating evidence from studies in humans and animal models has elucidated that gut microbiota, acting as a complex ecosystem, contributes critically to colorectal cancer (CRC). The potential mechanisms often reported emphasize the vital role of carcinogenic activities of specific pathogens, but in fact, a series of metabolites produced from exogenous dietary substrates or endogenous host compounds occupy a decisive position similarly. Detrimental gut microbiota-derived metabolites such as trimethylamine-N-oxide, secondary bile acids, hydrogen sulfide and N-nitroso compounds could reconstruct the ecological composition and metabolic activity of intestinal microorganisms and formulate a microenvironment that opens susceptibility to carcinogenic stimuli. They are implicated in the occurrence, progression and metastasis of CRC through different mechanisms, including inducing inflammation and DNA damage, activating tumorigenic signaling pathways and regulating tumor immunity. In this review, we mainly summarized the intimate relationship between detrimental gut microbiota-derived metabolites and CRC, and updated the current knowledge about detrimental metabolites in CRC pathogenesis. Then, multiple interventions targeting these metabolites for CRC management were critically reviewed, including diet modulation, probiotics/prebiotics, fecal microbiota transplantation, as well as more precise measures such as engineered bacteria, phage therapy and chemopreventive drugs. A better understanding of the interplay between detrimental microbial metabolites and CRC would hold great promise against CRC.

RevDate: 2021-11-04

Sahitya DSK, Jandiyal A, Jain A, et al (2021)

Prevention and management of carbapenem-resistant Enterobacteriaceae in haematopoietic cell transplantation.

Therapeutic advances in infectious disease, 8:20499361211053480 pii:10.1177_20499361211053480.

Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high morbidity and mortality rates in haematopoietic cell transplantation (HCT) recipients. Factors like mucositis, neutropenia, prolonged hospital stay, and frequent use of prophylactic antimicrobials make HCT recipients especially susceptible to CRE infections. Low culture positivity rates, delay in microbiological diagnosis, and resistance to empirical antimicrobial therapy for febrile neutropenia are responsible for high mortality rates in HCT recipients infected with CRE. In this review we discuss the epidemiology, diagnosis, and management of CRE infections with particular emphasis on patients undergoing HCT. We emphasise the need for preventive strategies like multidisciplinary antimicrobial stewardship, and pre-emptive screening for CRE colonisation in prospective HCT patients as measures to mitigate the adverse impact of CRE on HCT outcomes. Newer diagnostic tests like polymerase chain reaction and matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) assay that enable earlier and better identification of CRE isolates are discussed. Antimicrobial agents available against CRE, including newer agents like ceftazidime-avibactam and meropenem-vaborbactam, have been reviewed. We also discuss the data on promising experimental treatments against CRE: phage therapy and healthy donor faecal microbiota transplant. Finally, this review puts forth recommendations as per existing literature on diagnosis and management of CRE infections in blood and marrow transplant (BMT) unit.

RevDate: 2021-11-03

Davrandi M, Harris S, Smith PJ, et al (2021)

The Relationship Between Mucosal Microbiota, Colitis, and Systemic Inflammation in Chronic Granulomatous Disorder.

Journal of clinical immunology [Epub ahead of print].

PURPOSE: Chronic granulomatous disorder (CGD) is a primary immunodeficiency which is frequently complicated by inflammatory colitis and is associated with systemic inflammation. Herein, we aimed to investigate the role of the microbiome in the pathogenesis of colitis and systemic inflammation.

METHODS: We performed 16S rDNA sequencing on mucosal biopsy samples from each segment of 10 CGD patients' colons and conducted compositional and functional pathway prediction analyses.

RESULTS: The microbiota in samples from colitis patients demonstrated reduced taxonomic alpha-diversity compared to unaffected patients, even in apparently normal bowel segments. Functional pathway richness was similar between the colitic and non-colitic mucosa, although metabolic pathways involved in butyrate biosynthesis or utilization were enriched in patients with colitis and correlated positively with fecal calprotectin levels. One patient with very severe colitis was dominated by Enterococcus spp., while among other patients Bacteroides spp. abundance correlated with colitis severity measured by fecal calprotectin and an endoscopic severity score. In contrast, Blautia abundance is associated with low severity scores and mucosal health. Several taxa and functional pathways correlated with concentrations of inflammatory cytokines in blood but not with colitis severity. Notably, dividing patients into "high" and "low" systemic inflammation groups demonstrated clearer separation than on the basis of colitis status in beta-diversity analyses.

CONCLUSION: The microbiome is abnormal in CGD-associated colitis and altered functional characteristics probably contribute to pathogenesis. Furthermore, the relationship between the mucosal microbiome and systemic inflammation, independent of colitis status, implies that the microbiome in CGD can influence the inflammatory phenotype of the condition.

RevDate: 2021-11-01

Kellermayer R, Wu Q, Nagy-Szakal D, et al (2021)

Fecal Microbiota Transplantation Commonly Failed in Children with Co-Morbidities.

Journal of pediatric gastroenterology and nutrition pii:00005176-900000000-95495 [Epub ahead of print].

OBJECTIVES: Fecal microbiota transplantation (FMT) is arguably the most effective treatment for recurrent Clostridioides difficile infection (rCDI). Clinical reports on pediatric FMT have not systematically evaluated microbiome restoration in patients with co-morbidities. Here we determined whether FMT recipient age and underlying co-morbidity influenced clinical outcomes and microbiome restoration when treated from shared fecal donor sources.

METHODS: Eighteen rCDI patients participating in a single-center, open-label prospective cohort study received fecal preparation from a self-designated (single case) or two universal donors. Twelve age-matched healthy children and 4 pediatric ulcerative colitis (UC) cases from an independent serial FMT trial, but with a shared fecal donor were examined as controls for microbiome restoration using 16S rRNA gene sequencing of longitudinal fecal specimens.

RESULTS: FMT was significantly more effective in rCDI recipients without underlying chronic co-morbidities where fecal microbiome composition in post-transplant responders was restored to levels of healthy children. Microbiome reconstitution was not associated with symptomatic resolution in some rCDI patients who had co-morbidities. Significant elevation in Bacteroidaceae, Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae and Erysipelotrichaceae was consistently observed in pediatric rCDI responders, while Enterobacteriaceae decreased, correlating with augmented complex carbohydrate degradation capacity.

CONCLUSION: Recipient background disease was a significant risk factor influencing FMT outcomes. Special attention should be taken when considering FMT for pediatric rCDI patients with underlying co-morbidities.

RevDate: 2021-11-02

Sung JJY, SH Wong (2021)

What is unknown in using microbiota as a therapeutic?.

Journal of gastroenterology and hepatology [Epub ahead of print].

Fecal microbiota transplantation (FMT) has been used extensively in the treatment of various gastrointestinal and extraintestinal conditions, despite that there are still a lot of missing gaps in our knowledge in the gut microbiota and its behavior. This article describes the unknowns in microbiota biology (undetected microbes, uncertain colonization, unclear mechanisms of action, uncertain indications, unsure long-term efficacy, or side effects). We discuss how these unknowns may affect the therapeutic uses of FMT, and the potentials and caveats of other related microbiota-based therapies. When used as an experimental therapy or last resort in difficult conditions, caution should be taken against inadvertent complications. Clear documentations of post-treatment events should be made mandatory, classified, and graded as in clinical trials. Further robust scientific experiments and properly designed clinical studies are needed.

RevDate: 2021-11-01
CmpDate: 2021-11-01

Taghinezhad-S S, Mohseni AH, X Fu (2021)

Intervention on gut microbiota may change the strategy for management of colorectal cancer.

Journal of gastroenterology and hepatology, 36(6):1508-1517.

Dysbiosis in the gut microbiota composition due to environmental or genetic variations can disrupt the immune system and may promote several diseases such as colorectal cancer (CRC). Gut microbiota can alter the toxicity and efficiency of an extensive range of CRC treatment methods, especially surgery, chemotherapy, radiotherapy, and immunotherapy. The recent scientific evidence suggested that gut microbiota modulation exhibits an essential positive influence on inhibition and treatment of CRC. The literature survey revealed that modulating the gut microbiota composition by probiotics, prebiotics, and diets protects CRC patients from treatment-associated adverse effects. This review summarizes the recent advancements in the association between interventions on gut microbiota and CRC to provide innovative strategies for enhancing the safety and efficiency of CRC therapy.

RevDate: 2021-11-02
CmpDate: 2021-11-02

Olesen SW, Y Gerardin (2021)

Re-Evaluating the Evidence for Faecal Microbiota Transplantation 'Super-Donors' in Inflammatory Bowel Disease.

Journal of Crohn's & colitis, 15(3):453-461.

BACKGROUND: Faecal microbiota transplantation [FMT] is a recommended treatment for recurrent Clostridioides difficile infection, and there is promise that FMT may be effective for conditions such as inflammatory bowel disease [IBD]. Previous FMT clinical trials have considered the possibility of a 'donor effect', that is, that FMT material from different donors has different clinical efficacies.

METHODS: Here we re-evaluate evidence for donor effects in published FMT clinical trials for IBD.

RESULTS: In ten of 12 published studies, no statistically significant donor effect was detected when rigorously re-evaluating the original analyses. One study showed statistically significant separation of microbiota composition of pools of donor stool when stratified by patient outcome. One study reported a significant effect but did not have underlying data available for re-evaluation. When quantifying the uncertainty on the magnitude of the donor effect, confidence intervals were large, including both zero donor effects and very substantial donor effects.

CONCLUSION: Although we found very little evidence for donor effects, the existing data cannot rule out the possibility that donor effects are clinically important. Large clinical trials prospectively designed to detect donor effects are probably needed to determine if donor effects are clinically relevant for IBD.

RevDate: 2021-11-01

Chen T, Wang R, Duan Z, et al (2021)

Akkermansia muciniphila Protects Against Psychological Disorder-Induced Gut Microbiota-Mediated Colonic Mucosal Barrier Damage and Aggravation of Colitis.

Frontiers in cellular and infection microbiology, 11:723856.

Psychological disorders are associated with increased risk of severe inflammatory bowel disease (IBD) by causing gut microbiota dysbiosis and colonic mucosal barrier damage. However, the interaction between chronic restraint stress (CRS), gut microbiota composition, and colonic mucus remains unclear. We demonstrated that mice under CRS conditions exhibited alterations in microbiota composition, disruption of colonic mucus, and aggravation of colitis. In addition, the abundance of Akkermansia muciniphila was significantly decreased in mice under CRS and UC patients with depression, and positively associated with the expression of MUC2. After antibiotic treatment, the recipient mice colonized with CRS microbiota showed barrier defects and severe colitis. Administration of Akkermansia muciniphila was found to restore colonic mucus and modify the gut microbiota. We confirm that CRS-mediated gut microbiota dysbiosis results in colonic mucosal barrier damage and aggravation of colitis. Our results suggest that A. muciniphila is expected to be a potential probiotic to protect and treat colonic mucus that is involved in IBD with psychological disorders.

RevDate: 2021-11-01

Ma S, Wang N, Zhang P, et al (2021)

Fecal microbiota transplantation mitigates bone loss by improving gut microbiome composition and gut barrier function in aged rats.

PeerJ, 9:e12293 pii:12293.

Background: Gut microbiota (GM) dysbiosis is closely related to bone loss and the occurrence of osteoporosis in animals and human. However, little is known about the effect and the mechanisms of fecal microbiota transplantation (FMT) on bone in the treatment of senile osteoporosis.

Methods: Aged female rats were randomly divided into the FMT group and the control group. 3-month-old female rats were used as fecal donors. The rats were sacrificed at 12 and 24 weeks following transplantation and the serum, intestine, bone, and feces were collected for subsequent analyses.

Results: The bone turnover markers of osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), and carboxy-terminal peptide (CTX) decreased significantly at 12 and 24 weeks following FMT (P < 0.05). At 12 weeks following transplantation, histomorphometric parameters including the bone volume (BV), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) of the FMT group were comparable to the control group. However, at 24 weeks following transplantation, these parameters of the FMT group were significantly higher than those of the control group (P < 0.05). Besides, the GM aggregated at 12 and 24 weeks following FMT, and the ecological distance was close between the rats in the FMT group and the donor rats. Alpha diversity, shown by the Shannon index and Simpson index, and the Firmicutes/Bacteroidetes ratio decreased significantly after FMT at 24 weeks. Furthermore, FMT restored the GM composition in aged rats at the phylum and family level, and the intestinal microbiota of the aged rats was similar to that of the donor rats. Correlation network analysis indirectly suggested the causality of FMT on alleviating osteoporosis. FMT improved the intestinal structure and up-regulated the expression of tight junction proteins of occludin, claudin, and ZO-1, which might be associated with the protective effects of FMT on bone.

Conclusions: GM transplanted from young rats alleviated bone loss in aged rats with senile osteoporosis by improving gut microbiome composition and intestinal barrier function. These data might provide a scientific basis for future clinical treatment of osteoporosis through FMT.

RevDate: 2021-11-01

Hong MK, Liu HH, Chen GH, et al (2021)

Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury.

Oxidative medicine and cellular longevity, 2021:3259238.

Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Oridonin (OD), which is the major active ingredient of the traditional Chinese medicine Rabdosia rubescens, reportedly exerts anti-inflammatory and antioxidative effects. Here, we first find that OD protects against APAP-induced hepatotoxicity. The results of hepatic tissue-associated RNA-seq and metabolomics showed that the protective effects of OD were dependent upon urea cycle regulation. And such regulation of OD is gut microbiota partly dependent, as demonstrated by fecal microbiota transplantation (FMT). Furthermore, using 16S rRNA sequencing, we determined that OD significantly enriched intestinal Bacteroides vulgatus, which activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to regulate redox homeostasis against APAP by urea cycle. In conclusion, our study suggests that the Bacteroides vulgatus-urea cycle-Nrf2 axis may be a potential target for reducing APAP-induced liver injury, which is altered by OD.

RevDate: 2021-11-01

Zhong Y, Cao J, Deng Z, et al (2021)

Effect of Fiber and Fecal Microbiota Transplantation Donor on Recipient Mice Gut Microbiota.

Frontiers in microbiology, 12:757372.

Both fecal microbiota transplantation (FMT) and dietary fiber intervention were verified as effective ways to manipulate the gut microbiota, whereas little is known about the influence of the combined methods on gut microbiota. Here, we constructed "non-industrialized" and "industrialized" gut microbiota models to investigate the donor effect of FMT and diet effect in shaping the gut microbiota. Mice were transplanted fecal microbiota from domestic pig and received a diet with low-fiber (D) or high-fiber (DF), whereas the other two groups were transplanted fecal microbiota from wild pig and then received a diet with low-fiber (W) or high-fiber (WF), respectively. Gut microbiota of WF mice showed a lower Shannon and Simpson index (P < 0.05), whereas gut microbiota of W mice showed no significant difference than that of D and DF mice. Random forest models revealed the major differential bacteria genera between four groups, including Anaeroplasma or unclassified_o_Desulfovibrionales, which were influenced by FMT or diet intervention, respectively. Besides, we found a lower out-of-bag rate in the random forest model constructed for dietary fiber (0.086) than that for FMT (0.114). Linear discriminant analysis effective size demonstrated that FMT combined with dietary fiber altered specific gut microbiota, including Alistipes, Clostridium XIVa, Clostridium XI, and Akkermansia, in D, DF, W, and WF mice, respectively. Our results revealed that FMT from different donors coupled with dietary fiber intervention could lead to different patterns of gut microbiota composition, and dietary fiber might play a more critical role in shaping gut microbiota than FMT donor. Strategies based on dietary fiber can influence the effectiveness of FMT in the recipient.

RevDate: 2021-10-29

Niu M, P Chen (2021)

Crosstalk between gut microbiota and sepsis.

Burns & trauma, 9:tkab036 pii:tkab036.

Sepsis is an overwhelming inflammatory response to microbial infection. Sepsis management remains a clinical challenge. The role of the gut microbiome in sepsis has gained some attention. Recent evidence has demonstrated that gut microbiota regulate host physiological homeostasis mediators, including the immune system, gut barrier function and disease susceptibility pathways. Therefore, maintenance or restoration of microbiota and metabolite composition might be a therapeutic or prophylactic target against critical illness. Fecal microbiota transplantation and supplementation of probiotics are microbiota-based treatment methods that are somewhat limited in terms of evidence-based efficacy. This review focuses on the importance of the crosstalk between the gastrointestinal ecosystem and sepsis to highlight novel microbiota-targeted therapies to improve the outcomes of sepsis treatment.

RevDate: 2021-10-29

Zhou J, Hou C, Chen H, et al (2021)

P16 I NK 4a Deletion Ameliorates Damage of Intestinal Epithelial Barrier and Microbial Dysbiosis in a Stress-Induced Premature Senescence Model of Bmi-1 Deficiency.

Frontiers in cell and developmental biology, 9:671564.

This study aimed to determine whether Bmi-1 deficiency leads to intestinal epithelial barrier destruction and microbiota dysfunction, which members of the microbial community alter barrier function with age, and whether p16 INK4a deletion could reverse the damage of intestinal epithelial barrier and microbial dysbiosis. Intestines from Bmi-1-deficient (Bmi-1-/-), Bmi-1 and p16 INK4a double-knockout (Bmi-1-/-p16 INK4a-/-), and wild-type mice were observed for aging and inflammation. Duolink Proximity Ligation Assay, immunoprecipitation, and construction of p16 INK4a overexpressed adenovirus and the overexpressed plasmids of full-length, mutant, or truncated fragments for occludin were used for analyzing the interaction between p16 INK4a and occludin. High-throughput sequencing of V4 region amplicon of 16S ribosomal RNA was conducted using intestinal microbiota. We found Bmi-1 deficiency destructed barrier structure, barrier function, and tight junction (TJ) in intestinal epithelium; decreased the TJ proteins; increased tumor necrosis factor α (TNF-α)-dependent barrier permeability; and up-regulated proinflammatory level of macrophages induced by intestinal microbial dysbiosis. The transplantation of fecal microbiota from wild-type mice ameliorated TJ in intestinal epithelium of Bmi-1-/- and Bmi-1-/-p16 INK4a-/- mice. Harmful bacteria including Desulfovibrio, Helicobacter, and Oscillibacter were at a higher level in Bmi-1-/- mice. More harmful bacteria Desulfovibrio entered the epithelium and promoted macrophages-secreted TNF-α and caused TNF-α-dependent barrier permeability and aging. Accumulated p16 INK4a combined with occludin at the 1st-160th residue in cytoplasm of intestinal epithelium cells from Bmi-1-/- mice, which blocked formation of TJ and the repair of intestinal epithelium barrier. P16 INK4a deletion could maintain barrier function and microbiota balance in Bmi-1-/- mice through strengthening formation of TJ and decreasing macrophages-secreted TNF-α induced by Desulfovibrio entering the intestinal epithelium. Thus, Bmi-1 maintained intestinal TJ, epithelial barrier function, and microbiota balance through preventing senescence characterized by p16 INK4a accumulation. The clearance of p16 INK4a -positive cells in aging intestinal epithelium would be a new method for maintaining barrier function and microbiota balance. The residues 1-160 of occludin could be a novel therapeutic target for identifying small molecular antagonistic peptides to prevent the combination of p16 INK4a with occludin for protecting TJ.

RevDate: 2021-10-29

Lauriero G, Abbad L, Vacca M, et al (2021)

Fecal Microbiota Transplantation Modulates Renal Phenotype in the Humanized Mouse Model of IgA Nephropathy.

Frontiers in immunology, 12:694787.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. Several observations suggest that gut microbiota could be implicated in IgAN pathophysiology. Aiming at exploring whether microbiota modulation is able to influence disease outcome, we performed fecal microbiota transplantation (FMT) from healthy controls (HC-sbjs), non-progressor (NP-pts) and progressor (P-pts) IgAN patients to antibiotic-treated humanized IgAN mice (α1KI-CD89Tg), by oral gavage. FMT was able to modulate renal phenotype and inflammation. On one hand, the microbiota from P-pts was able to induce an increase of serum BAFF and galactose deficient-IgA1 levels and a decrease of CD89 cell surface expression on blood CD11b+ cells which was associated with soluble CD89 and IgA1 mesangial deposits. On the other hand, the microbiota from HC-sbjs was able to induce a reduction of albuminuria immediately after gavage, an increased cell surface expression of CD89 on blood CD11b+ cells and a decreased expression of KC chemokine in kidney. Higher serum BAFF levels were found in mice subjected to FMT from IgAN patients. The main bacterial phyla composition and volatile organic compounds profile significantly differed in mouse gut microbiota. Microbiota modulation by FMT influences IgAN phenotype opening new avenues for therapeutic approaches in IgAN.

RevDate: 2021-10-29

Lythgoe MP, Ghani R, Mullish BH, et al (2021)

The potential of fecal microbiota transplantation in oncology.

Trends in microbiology pii:S0966-842X(21)00243-2 [Epub ahead of print].

Immune checkpoint inhibitors (ICPIs) are efficacious treatments for several cancers. However, most patients fail to demonstrate durable complete responses. The gut microbiome composition influences the ICPI response. Two recent proof-of-concept studies have demonstrated the utility of fecal microbiota transplantation to transform ICPI responsiveness in refractory patients, providing intriguing evidence for the future of microbiota modulation within oncology.

RevDate: 2021-10-29
CmpDate: 2021-10-29

Hirten RP, BE Sands (2021)

New Therapeutics for Ulcerative Colitis.

Annual review of medicine, 72:199-213.

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon with a variable course. Despite advances in treatment, only approximately 40% of patients achieve clinical remission at the end of a year, prompting the exploration of new treatment modalities. This review explores novel therapeutic approaches to UC, including promising drugs in various stages of development, efforts to maximize the efficacy of currently available treatment options, and non-medication-based modalities. Treatment approaches which show promise in impacting the future of UC management are highlighted.

RevDate: 2021-10-28

Ianiro G, Bibbò S, Porcari S, et al (2021)

Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: experience of a large-volume European FMT center.

Gut microbes, 13(1):1994834.

Inflammatory bowel disease (IBD) is a risk factor for C. difficile infection (CDI), which, in turn, complicates the clinical course of IBD. Fecal microbiota transplantation (FMT) is safe and effective in patients with IBD and recurrent CDI (rCDI). In our study, patients with IBD and rCDI received FMT by colonoscopy and were followed-up for 8 weeks. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Eighteen patients with IBD were enrolled. Eight patients received sequential FMT either for pseudomembranous colitis or failure of single fecal infusion. At 8-week follow-up the C. difficile toxin was negative in 17 patients, and most (83%) experienced also improvement of IBD disease activity. Overall, we did not observe any serious adverse event.FMT appears to be highly effective and safe in patients with IBD and rCDI and is likely not only to eradicate CDI but also to improve disease activity of IBD.

RevDate: 2021-10-28

Xie J, Li LF, Dai TY, et al (2021)

Short-chain fatty acids produced by Ruminococcaceae mediates α-Linolenic acid promote intestinal stem cells proliferation.

Molecular nutrition & food research [Epub ahead of print].

SCOPE: The proliferation and differentiation of intestinal stem cells (ISCs) are the basis of intestinal renewal and regeneration, and gut microbiota plays an important role in it. Dietary nutrition has the effect of regulating the activity of ISCs, however, the regulation effect of α-linolenic acid (ALA) has seldom been reported.

METHODS AND RESULTS: After intervening mice with different doses of ALA for 30 days, we found that ALA (0.5 g/kg) promoted small intestinal and villus growth by activating the Wnt/β-catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increased the abundance of the Ruminococcaceae and Prevotellaceae, and promoted the produce of short-chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrated that ALA on the proliferation of ISCs are gut microbiota dependent, among them the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate showed a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigated 5-fluorouracil-induced intestinal mucosal damage by promoting ISCs proliferation.

CONCLUSION: These results indicate that SCFAs produced by Ruminococcaceae mediates ALA promote ISCs proliferation by activating Wnt/β-catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis. This article is protected by copyright. All rights reserved.

RevDate: 2021-10-28

Lin D, Hu B, Li P, et al (2021)

Roles of the intestinal microbiota and microbial metabolites in acute GVHD.

Experimental hematology & oncology, 10(1):49.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most curative strategies for the treatment of many hematologic malignancies and diseases. However, acute graft-versus-host disease (GVHD) limits the success of allo-HSCT. The prevention and treatment of acute GVHD is the key issue for improving the efficacy of allo-HSCT and has become a research hotspot. The intestine is the primary organ targeted by acute GVHD, and the intestinal microbiota is critical for maintaining the homeostasis of the intestinal microenvironment and the immune response. Many studies have demonstrated the close association between the intestinal microbiota and the pathogenesis of acute GVHD. Furthermore, dysbiosis of the microbiota, which manifests as alterations in the diversity and composition of the intestinal microbiota, and alterations of microbial metabolites are pronounced in acute GVHD and associated with poor patient prognosis. The microbiota interacts with the host directly via microbial surface antigens or microbiota-derived metabolites to regulate intestinal homeostasis and the immune response. Therefore, intervention strategies targeting the intestinal microbiota, including antibiotics, prebiotics, probiotics, postbiotics and fecal microbiota transplantation (FMT), are potential new treatment options for acute GVHD. In this review, we discuss the alterations and roles of the intestinal microbiota and its metabolites in acute GVHD, as well as interventions targeting microbiota for the prevention and treatment of acute GVHD.

RevDate: 2021-10-28
CmpDate: 2021-10-28

Palma Albornoz SP, Fraga-Silva TFC, Gembre AF, et al (2021)

Obesity-Induced Dysbiosis Exacerbates IFN-γ Production and Pulmonary Inflammation in the Mycobacterium tuberculosis Infection.

Cells, 10(7):.

The microbiota of the gut-lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4+IFN-γ+IL-17- cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut-lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology.

RevDate: 2021-10-27

Jan N, Hays RA, Oakland DN, et al (2021)

Fecal Microbiota Transplantation Increases Colonic IL-25 and Dampens Tissue Inflammation in Patients with Recurrent Clostridioides difficile.

mSphere, 6(5):e0066921.

Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility, and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of interleukin 25 (IL-25) and that FMT protected in part by restoring IL-25 signaling. Here, we conducted a prospective study in humans to test if FMT induced IL-25 expression in the colons of patients with recurrent CDI (rCDI). Colonic biopsy specimens and blood were collected at the time of FMT and 60 days later. Colon biopsy specimens were analyzed for IL-25 protein levels, total tissue transcriptome, and epithelium-associated microbiota before and after FMT, and peripheral immune cells were immunophenotyped. FMT increased alpha diversity of the colonic microbiota and levels of IL-25 in colonic tissue. In addition, FMT increased expression of homeostatic genes and repressed inflammatory genes. Finally, circulating Th17 cells were decreased post-FMT. The increase in levels of the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity. IMPORTANCE Fecal microbiota transplantation (FMT) is an effective treatment for C. difficile infection for most patients; however, introducing a complex mixture of microbes also has had unintended consequences for some patients. Attempts to create a standardized probiotic therapeutic that recapitulates the efficacy of FMT have been unsuccessful to date. We sought to understand what immune markers are changed in patients undergoing FMT to treat recurrent C. difficile infection and identified an immune signaling molecule, IL-25, that was restored by FMT. This finding indicates that adjunctive therapy with IL-25 could be useful in treating C. difficile infection.

RevDate: 2021-10-27
CmpDate: 2021-10-27

de Stefano MC, Mazzanti B, Vespasiano F, et al (2021)

The Italian National Faecal Microbiota Transplantation Program: a coordinated effort against Clostridioides difficile infection.

Annali dell'Istituto superiore di sanita, 57(3):239-243.

Clostridioides (previously Clostridium) difficile infection (CDI) is a common cause of antibiotic-associated diarrhea, whose symptoms range from mild diarrhea to life-threatening pseudomembranous colitis. CDI is characterized by significant recurrence rate following initial resolution and recurrent C. difficile infection (rCDI) represents an onerous burden for the healthcare systems. Conventional antibiotic-based approaches are generally used for the treatment of rCDI but the effective therapy remains elusive. Recently, the faecal microbiota transplantation (FMT) has emerged as an alternative therapeutic strategy against rCDI, with high treatment success rate. In 2018, the Italian National FMT Program was launched, with the aim to provide high quality standards in FMT application to adults with rCDI not responding to antibiotic therapy. Here, we sketch out the key characteristics and the progress of the Italian National FMT Program during the COVID-19 pandemic.

RevDate: 2021-10-27
CmpDate: 2021-10-27

Verbeke F, B De Spiegeleer (2021)

Faecal microbiota transplants: Why do we not consider them as Advanced Therapy Medicinal Products?.

United European gastroenterology journal, 9(4):519-520.

RevDate: 2021-10-27
CmpDate: 2021-10-27

Khanna S (2021)

Microbiota restoration for recurrent Clostridioides difficile: Getting one step closer every day!.

Journal of internal medicine, 290(2):294-309.

Clostridioides difficile infection (CDI) is an urgent health threat being the most common healthcare-associated infection, and its management is a clinical conundrum. Over 450 000 infections are seen in the United States with similar incidence seen in the rest of the developed world. The majority of infections seen are mild-moderate with fulminant disease and mortality being rare complications seen in the elderly and in those with comorbidities. The most common complication of CDI is recurrent infection with rates as high as 60% after three or more infections. A dilemma in the management of primary and recurrent CDI is testing due to the high sensitivity of the nucleic acid amplification tests such as the polymerase chain reaction, which leads to clinical false positives if patients are not chosen carefully (with symptoms) before testing. A newer testing regimen involving a 2-step strategy is emerging using glutamate dehydrogenase as a screening strategy followed by enzyme immunoassay for the C. difficile toxin. Microbiota restoration therapies are the cornerstone of management of recurrent CDI to prevent future recurrences. The most common modality of microbiota restoration is faecal microbiota transplantation, which has been tainted with heterogeneity and adverse events such as serious infectious transmission. The success rates for recurrence prevention from microbiota restoration therapies are over 90% compared with less than 50% of recurrence prevention with courses of antibiotics. This has led to development and emergence of standardized microbiota restoration therapies in capsule and enema forms. Capsule-based therapies include CP101 (positive phase II results), RBX7455 (positive phase I results), SER-109 (positive phase III results) and VE303 (ongoing phase II trial). Enema-based therapy includes RBX2660 (positive phase III data). This review summarizes the principles of management and diagnosis of CDI and focuses on emerging and existing data on faecal microbiota transplantation and standardized microbiota restoration therapies.

RevDate: 2021-10-26

Mehmood K, Moin A, Hussain T, et al (2021)

Can manipulation of gut microbiota really be transformed into an intervention strategy for cardiovascular disease management?.

Folia microbiologica [Epub ahead of print].

Recent advancement in manipulation techniques of gut microbiota either ex vivo or in situ has broadened its plausible applicability for treating various diseases including cardiovascular disease. Several reports suggested that altering gut microbiota composition is an effective way to deal with issues associated with managing cardiovascular diseases. However, actual translation of gut microbiota manipulation-based techniques into cardiovascular-therapeutic approach is still questionable. This review summarized the evidence on challenges, opportunities, recent development, and future prospects of gut microbiota manipulation for targeting cardiovascular diseases. Initially, issues associated with current cardiovascular diseases treatment strategy, association of gut microbiota with cardiovascular disease, and its influence on cardiovascular drugs were discussed, followed by applicability of gut microbiota manipulation as a cardiovascular disease intervention strategy along with its challenges and future prospects. Despite the fact that the gut microbiota is rugged, interventions like probiotics, prebiotics, synbiotics, fecal microbiota transplantation, fecal virome transplantation, antibiotics, diet changes, and exercises could manipulate it. Advanced techniques like administration of engineered bacteriophages and bacteria could also be employed. Intensive exploration revealed that if sufficiently controlled approach and proper monitoring were applied, gut microbiota could provide a compelling answer for cardiovascular therapy.

RevDate: 2021-10-26

Li N, Dai Z, Wang Z, et al (2021)

Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease.

Respiratory research, 22(1):274.

BACKGROUND: Dysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood.

METHODS: We carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity. Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28 days to induce pulmonary changes. Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes.

RESULTS: We observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids. After 28 days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation. Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20 weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed.

CONCLUSION: These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.

RevDate: 2021-10-25

Alagiakrishnan K, T Halverson (2021)

Microbial Therapeutics in Neurocognitive and Psychiatric Disorders.

Journal of clinical medicine research, 13(9):439-459.

Microbial therapeutics, which include gut biotics and fecal transplantation, are interventions designed to improve the gut microbiome. Gut biotics can be considered as the administration of direct microbial populations. The delivery of this can be done through live microbial flora, certain food like fiber, microbial products (metabolites and elements) obtained through the fermentation of food products, or as genetically engineered substances, that may have therapeutic benefit on different health disorders. Dietary intervention and pharmacological supplements with gut biotics aim at correcting disruption of the gut microbiota by repopulating with beneficial microorganism leading to decrease in gut permeability, inflammation, and alteration in metabolic activities, through a variety of mechanisms of action. Our understanding of the pharmacokinetics of microbial therapeutics has improved with in vitro models, sampling techniques in the gut, and tools for the reliable identification of gut biotics. Evidence from human studies points out that prebiotics, probiotics and synbiotics have the potential for treating and preventing mental health disorders, whereas with paraprobiotics, proteobiotics and postbiotics, the research is limited at this point. Some animal studies point out that gut biotics can be used with conventional treatments for a synergistic effect on mental health disorders. If future research shows that there is a possibility of synergistic effect of psychotropic medications with gut biotics, then a gut biotic or nutritional prescription can be given along with psychotropics. Even though the overall safety of gut biotics seems to be good, caution is needed to watch for any known and unknown side effects as well as the need for risk benefit analysis with certain vulnerable populations. Future research is needed before wide spread use of natural and genetically engineered gut biotics. Regulatory framework for gut biotics needs to be optimized. Holistic understanding of gut dysbiosis, along with life style factors, by health care providers is necessary for the better management of these conditions. In conclusion, microbial therapeutics are a new psychotherapeutic approach which offer some hope in certain conditions like dementia and depression. Future of microbial therapeutics will be driven by well-done randomized controlled trials and longitudinal research, as well as by replication studies in human subjects.

RevDate: 2021-10-25

Fu X, Chen T, Cai J, et al (2021)

The Microbiome-Gut-Brain Axis, a Potential Therapeutic Target for Substance-Related Disorders.

Frontiers in microbiology, 12:738401.

Substance addiction is a complex worldwide public health problem. It endangers both personal life and social stability, causing great loss on economy. Substance-related disorder is considered to be a complicated chronic brain disorder. It resulted from interactions among pharmacological properties of addictive substances, individual susceptibility, and social-environmental factors. Unfortunately, there is still no ideal treatment for this disorder. Recent lines of evidence suggest that gut microbiome may play an important role in the pathogenesis of neuropsychiatric disorders, including substance-related disorders. This review summarizes the research on the relationship between gut microbiome and substance-related disorders, including different types of substance, different individual susceptibility, and the occurrence and development of substance-induced mental disorders. We also discuss the potentiation of gut microbiome in the treatment of substance-related disorders, especially in the treatment of substance-induced mental disorders and manipulation on individuals' responsiveness to addictive substances.

RevDate: 2021-10-25

Zhang X, Li N, Chen Q, et al (2021)

Fecal Microbiota Transplantation Modulates the Gut Flora Favoring Patients With Functional Constipation.

Frontiers in microbiology, 12:700718.

Intestinal dysmotility is common in many diseases and is correlated with gut microbiota dysbiosis and systemic inflammation. Functional constipation (FC) is the most typical manifestation of intestinal hypomotility and reduces patients' quality of life. Some studies have reported that fecal micriobiota transplantation (FMT) may be an effective and safe therapy for FC as it corrects intestinal dysbiosis. This study was conducted to evaluate how FMT remodels the gut microbiome and to determine a possible correlation between certain microbes and clinical symptoms in constipated individuals. Data were retrospectively collected on 18 patients who underwent FMT between January 1, 2019 and June 30, 2020. The fecal bacterial genome was detected by sequencing the V3-V4 hypervariable regions of the 16S rDNA gene. Fecal short chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry, and serum inflammatory factor concentrations were detected via enzyme-linked immunosorbent assay. Comparing the changes in fecal microbiome compositions before and after FMT revealed a significant augmentation in the alpha diversity and increased abundances of some flora such as Clostridiales, Fusicatenibacter, and Paraprevotella. This was consistent with the patients experiencing relief from their clinical symptoms. Abundances of other flora, including Lachnoanaerobaculum, were decreased, which might correlate with the severity of patients' constipation. Although no differences were found in SCFA production, the butyric acid concentration was correlated with both bacterial alterations and clinical symptoms. Serum IL-8 levels were significantly lower after FMT than at baseline, but IL-4, IL-6, IL-10, and IL-12p70 levels were not noticeably changed. This study showed how FMT regulates the intestinal microenvironment and affects systemic inflammation in constipated patients, providing direction for further research on the mechanisms of FMT. It also revealed potential microbial targets for precise intervention, which may bring new breakthroughs in treating constipation.

RevDate: 2021-10-25
CmpDate: 2021-10-25

Fehily SR, Basnayake C, Wright EK, et al (2021)

The gut microbiota and gut disease.

Internal medicine journal, 51(10):1594-1604.

The gut microbiota has a key role in the maintenance of good health, and in the pathogenesis of gastrointestinal diseases. These conditions include the inflammatory bowel diseases, colorectal cancer, coeliac disease and metabolic liver disease. Although the nature of the microbial disturbance in these conditions has not been fully characterised, this has not prevented the development of microbially based therapies. Microbial-changing therapies may address newly recognised pathophysiological contributors of disease and have the potential to replace or supplement standard therapies. Antibiotics play a role in initial Clostridiodes difficile disease and some specific inflammatory disorders. Probiotics have a more limited proven role. Faecal microbiota transplantation is of proven therapeutic benefit in recurrent C. difficile disease and ulcerative colitis. We review the current literature for microbiota-targeted therapies in gut disorders.

RevDate: 2021-10-22

van Prehn J, Reigadas E, Vogelzang EH, et al (2021)

European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases pii:S1198-743X(21)00568-1 [Epub ahead of print].

SCOPE: In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as fecal microbiota transplantation (FMT) and toxin-binding monoclonal antibodies, prompted the ESCMID study group on C. difficile (ESGCD) to update the 2014 treatment guidance document for CDI in adults.

METHODS AND QUESTIONS: Key questions on CDI treatment were formulated by the guideline committee and included: what is the best treatment for initial, severe, severe-complicated, refractory, recurrent and multiple recurrent CDI; what is the best treatment when no oral therapy is possible; can prognostic factors identify patients at risk for severe and recurrent CDI; and is there a place for CDI prophylaxis? Outcome measures for treatment strategy were: clinical cure, recurrence, and sustained cure. For studies on surgical interventions and severe-complicated CDI the outcome was mortality. Appraisal of available literature and drafting of recommendations was performed by the guideline drafting group. The total body of evidence for the recommendations on CDI treatment consists of the literature described in the previous guidelines, supplemented with a systematic literature search on randomized clinical trials and observational studies from 2012 and onwards. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The guideline committee was invited to comment on the recommendations. The guideline draft was sent to external experts and a patients' representative for review. Full ESCMID endorsement was obtained after a public consultation procedure.

RECOMMENDATIONS: Important changes compared with previous guideline include but are not limited to: (1) metronidazole is no longer recommended for treatment of CDI when fidaxomicin or vancomycin are available, (2) fidaxomicin is the preferred agent for treatment of initial CDI and the first recurrence of CDI when available and feasible, (3) FMT or bezlotoxumab in addition to Standard of Care antibiotics (SoC) are preferred for treatment of a second or further recurrence of CDI, (4) bezlotoxumab in addition to SoC is recommended for the first recurrence of CDI when fidaxomicin was used to manage the initial CDI episode, and (5) bezlotoxumab is considered as an ancillary treatment to vancomycin for a CDI episode with high risk of recurrence when fidaxomicin is not available. Contrary to the previous guideline, in the current guideline emphasis is placed on risk for recurrence as a factor that determines treatment strategy for the individual patient, rather than the disease severity.

RevDate: 2021-10-23

Zheng Y, Ding Y, Xu M, et al (2021)

Gut Microbiota Contributes to Host Defense Against Klebsiella pneumoniae-Induced Liver Abscess.

Journal of inflammation research, 14:5215-5225.

Purpose: Klebsiella pneumoniae-induced liver abscess (KLA) is a type of pyogenic liver abscess (PLA), which is a distinct invasive syndrome that has been increasingly reported worldwide over the past two decades. The intestinal microbiota is increasingly recognized as an important modulator that can promote and maintain host immune homeostasis. However, its precise role in liver abscess is unknown. We aimed to investigate the function of the gut microbiota in the host defense against K. pneumoniae infection.

Methods: We constructed C57BL/6J mice with KLA and analyzed the diversity and richness of the intestinal microflora by 16S rRNA sequencing. Next, to create a microbiota-depleted (MD) mouse model, we administered multiple broad-spectrum antibiotics and validated the model using 16S rRNA sequencing. At 48 h after K. pneumoniae infection, we assessed the general health condition, liver injury, bacterial loads, and inflammatory factor levels in MD+KLA mice. Additionally, fecal microbiota transplantation (FMT) was conducted in another group of MD+KLA mice prior to K. pneumoniae infection, and we assessed whether the transplantation changed the outcomes.

Results: The diversity of the intestinal flora was significantly changed in KLA mice compared to control mice, with a decrease in beneficial bacteria and an increase in harmful bacteria. The MD+KLA mice exhibited impaired antimicrobial capacity, reduced survival, increased inflammation and liver damage at 48 h after K. pneumoniae infection compared to the KLA mice. However, FMT normalized the inflammatory cytokine levels, reduced liver damage, and increased survival.

Conclusion: This study identified the gut microbiota as a protective factor against K. pneumoniae infection. The role of FMT in KLA should be investigated in future clinical studies.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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E-mail: RJR8222@gmail.com

Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

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Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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