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 |
| |
| Authors: | Tanya Monaghan Benjamin H Mullish Jordan Patterson Gane KS Wong Julian R Marchesi Huiping Xu |
| |
| Affiliation: | 1. NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK;2. Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK;3. Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada;4. BGI-Shenzhen, Shenzhen, China;5. Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada;6. School of Biosciences, Cardiff University, Cardiff, UK;7. Department of Biostatistics, Indiana University School of Medicine, Bloomington, Indiana, USA |
| |
| 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 fecal microbiota transplantation (FMT) recurrent Clostridium difficile infection (rCDI) bile acid metabolism fibroblast growth factor (FGF)19 |
|
|
