Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway

Gut Microbes. 2019;10(2):142-148. doi: 10.1080/19490976.2018.1506667. Epub 2018 Sep 5.

Abstract

The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.

Keywords: Microbiota; bile acid metabolism; fecal microbiota transplantation (FMT); fibroblast growth factor (FGF)19; recurrent infection (rCDI).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bile Acids and Salts / metabolism*
  • Clostridioides difficile / genetics
  • Clostridium Infections / metabolism
  • Clostridium Infections / therapy*
  • Fecal Microbiota Transplantation*
  • Feces / chemistry
  • Feces / microbiology
  • Female
  • Fibroblast Growth Factors / metabolism*
  • Gastrointestinal Microbiome / genetics
  • Humans
  • Male
  • Middle Aged
  • Proteome / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Recurrence
  • Signal Transduction*
  • Treatment Outcome
  • Weight Gain

Substances

  • Bile Acids and Salts
  • FGF19 protein, human
  • Proteome
  • Receptors, Cytoplasmic and Nuclear
  • fibroblast growth factor 21
  • farnesoid X-activated receptor
  • Fibroblast Growth Factors