Donor fecal microbiota transplantation alters gut microbiota and metabolites in obese individuals with steatohepatitis

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Documents

  • Julia J Witjes
  • Loek P Smits
  • Ceyda Tugba Pekmez
  • Andrei Prodan
  • Abraham S Meijnikman
  • Marian A Troelstra
  • Kristien E C Bouter
  • Hilde Herrema
  • Evgeni Levin
  • Adriaan G Holleboom
  • Maaike Winkelmeijer
  • Ulrich H Beuers
  • Krijn van Lienden
  • Judith Aron-Wisnewky
  • Ville Mannisto
  • Jacques J Bergman
  • Jurgen H Runge
  • Aart J Nederveen
  • Prokopis Konstanti
  • Erwin G Zoetendal
  • Willem de Vos
  • Joanne Verheij
  • Albert K Groen
  • Max Nieuwdorp

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.

Original languageEnglish
JournalHepatology Communications
Volume4
Issue number11
Pages (from-to)1578-1590
Number of pages13
DOIs
Publication statusPublished - 2020

Bibliographical note

© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.

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