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

Monaghan, Tanya M.; Mullish, Benjamin H.; Patterson, Jordan; Wong, Gane K.S.; Marchesi, Julian R.; Xu, Huiping; Tahseen, Jilani; Kao, Dina

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.

Citation

Monaghan, T. M., Mullish, B. H., Patterson, J., Wong, G. K., Marchesi, J. R., Xu, H., Tahseen, J., & Kao, D. (2018). 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. Gut Microbes, https://doi.org/10.1080/19490976.2018.1506667

• Journal Article Type: Article
• Acceptance Date: Jul 25, 2018
• Online Publication Date: Sep 5, 2018
• Publication Date: Sep 5, 2018
• Deposit Date: Jul 23, 2018
• Publicly Available Date: Sep 6, 2019
• Journal: Gut Microbes
• Print ISSN: 1949-0976
• Electronic ISSN: 1949-0984
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1080/19490976.2018.1506667
• Keywords: microbiota; fecal microbiota transplantation (FMT); recurrent Clostridium difficile infection; (rCDI); bile acid metabolism; fibroblast growth factor (FGF)19
• Public URL: https://nottingham-repository.worktribe.com/output/947614
• Additional Information: This is an Accepted Manuscript of an article published by Taylor & Francis in Gut microbes on 05/09/2018, available online: https://www.tandfonline.com/doi/full/10.1080/19490976.2018.1506667
• Contract Date: Jul 23, 2018