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

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 ph...

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Bibliographic Details
Main Authors: Monaghan, Tanya M., Mullish, Benjamin H., Patterson, Jordan, Wong, Gane K.S., Marchesi, Julian R., Xu, Huiping, Tahseen, Jilani, Kao, Dina
Format: Article
Published: Taylor & Francis 2018
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Online Access:https://eprints.nottingham.ac.uk/53079/
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Summary: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.