A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome

Ling Zhao, Wei Yang, Yang Chen, Fengjie Huang, Lin Lu, Chengyuan Lin, Tao Huang, Ziwan Ning, Lixiang Zhai, Lidan ZHONG, Waiching Lam, Zhen Yang, Xuan Zhang, Chungwah Cheng, Lijuan Han, Qinwei Qiu, Xiaoxiao Shang, Runyue Huang, Haitao XIAO, Zhenxing RenDongfeng Chen, Silong Sun, Hani El-Nezami, Zongwei CAI, Aiping LYU, Xiaodong Fang, Wei JIA, Zhaoxiang BIAN*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.

Original languageEnglish
Pages (from-to)438-450
Number of pages13
JournalJournal of Clinical Investigation
Volume130
Issue number1
DOIs
Publication statusPublished - 2 Jan 2020

Scopus Subject Areas

  • Medicine(all)

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