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Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.

ABSTRACT: The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of . Conclusion: Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.

SUBMITTER: Witjes JJ

PROVIDER: S-EPMC7603524 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.

Witjes Julia J JJ Smits Loek P LP Pekmez Ceyda T CT Prodan Andrei A Meijnikman Abraham S AS Troelstra Marian A MA Bouter Kristien E C KEC Herrema Hilde H Levin Evgeni E Holleboom Adriaan G AG Winkelmeijer Maaike M Beuers Ulrich H UH van Lienden Krijn K Aron-Wisnewky Judith J Mannisto Ville V Bergman Jacques J JJ Runge Jurgen H JH Nederveen Aart J AJ Dragsted Lars O LO Konstanti Prokopis P Zoetendal Erwin G EG de Vos Willem W Verheij Joanne J Groen Albert K AK Nieuwdorp Max M

Hepatology communications 20201007 11

The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. W ...[more]

PMID: 33163830

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Project description:UnlabelledClostridium difficile infection is one of the most common health care-associated infections, and up to 40% of patients suffer from recurrence of disease following standard antibiotic therapy. Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection. It is hypothesized that FMT aids in recovery of a microbiota capable of colonization resistance to C. difficile. However, it is not fully understood how this occurs. Here we investigated changes in the fecal microbiota structure following FMT in patients with recurrent C. difficile infection, and imputed a hypothetical functional profile based on the 16S rRNA profile using a predictive metagenomic tool. Increased relative abundance of Bacteroidetes and decreased abundance of Proteobacteria were observed following FMT. The fecal microbiota of recipients following transplantation was more diverse and more similar to the donor profile than the microbiota prior to transplantation. Additionally, we observed differences in the imputed metagenomic profile. In particular, amino acid transport systems were overrepresented in samples collected prior to transplantation. These results suggest that functional changes accompany microbial structural changes following this therapy. Further identification of the specific community members and functions that promote colonization resistance may aid in the development of improved treatment methods for C. difficile infection.ImportanceWithin the last decade, Clostridium difficile infection has surpassed other bacterial infections to become the leading cause of nosocomial infections. Antibiotic use, which disrupts the gut microbiota and its capability in providing colonization resistance against C. difficile, is a known risk factor in C. difficile infection. In particular, recurrent C. difficile remains difficult to treat with standard antibiotic therapy. Fecal microbiota transplantation (FMT) has provided a successful treatment method for some patients with recurrent C. difficile infection, but its mechanism and long-term effects remain unknown. Our results provide insight into the structural and potential metabolic changes that occur following FMT, which may aid in the development of new treatment methods for C. difficile infection.

Project description:Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria. Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT. Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group. Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.

Dataset Information

Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.

Publications

Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.

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