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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

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 Thumbnail


Authors

TANYA MONAGHAN Tanya.Monaghan@nottingham.ac.uk
Clinical Associate Professor in Luminal Gastroenterology

Benjamin H. Mullish

Jordan Patterson

Gane K.S. Wong

Julian R. Marchesi

Huiping Xu

Jilani Tahseen

Dina Kao



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., …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

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