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Cited by 202Gut microbiota and healthGastrointestinal motility and disordersInflammatory Bowel Disease

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

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Zhao, Ling, Yang, Wei, Chen, Yang, Huang, Fengjie, Lu, Lin, Lin, Chengyuan, Huang, Tao, Ning, Ziwan +20 more·2019·Journal of Clinical Investigation
DOI 10.1172/jci130976PMC PMC6934182

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Abstract

ABSTRACT Objective 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 remains unclear. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. Design Metabolomic and metagenomic analyses were performed of specimens from 290 IBS-D patients and 89 healthy volunteers. By transplanting human microbiota and manipulating specific microbiome species in mice, the effects of microbiota on host BA metabolism were assessed at metabolic, genetic and protein levels. Effects of individual and mixed BAs on enterohepatic feedback pathways were also tested in vitro and in vivo . Results Total fecal BAs were excessively excreted in 24.5% of IBS-D patients. Their fecal metagenomes showed increased abundances of Clostridia and BA-transforming genes ( hdhA and bais ). The increases of Clostridia bacteria (e.g. C. scindens ) were positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), while being negatively correlated with serum fibroblast growth factor 19 (FGF19). Both Clostridia -rich human microbiota and C. scindens enhanced levels of serum C4 and hepatic conjugated BAs in mice recipients and reduced ileal FGF19 expression. Inhibition of Clostridium species by vancomycin yielded opposite findings. Clostridia -derived BAs (e.g. conjugated and free ursodeoxycholic acid) significantly suppressed intestinal FGF19 expression. Conclusion The Clostridia -rich microbiota contributes to excessive BA excretion in IBS-D patients. This study provided the basis for more precise clinical diagnosis and management for IBS-D.

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  • In PI-IBS neuronal signalling remained sensitised 2 years after the infection.

    “For example, in PI-IBS neuronal signalling remained sensitised 2 years after the infection. 53”

    From Irritable bowel syndrome (2020) · cites this paper as [53]

    The Introduction discusses bile acids and visceral hypersensitivity in IBS-D, while the Results examine bile-acid excretion; neither addresses neuronal signalling in post-infectious IBS. Searches for PI-IBS, neuronal sensitisation, and a two-year period after infection found no supporting passage in our copy. Page numbers were not provided. (LLM, conf=0.76)

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Authors
Zhao, L., Yang, W., Chen, Y., Huang, F., Lu, L., Lin, C., Huang, T., Ning, Z., Zhai, L., Zhong, L. L. D., Lam, W., Yang, Z., Zhang, X., Cheng, C., Han, L., Qiu, Q., Shang, X., Huang, R., Xiao, H., Ren, Z., Chen, D., Sun, S., El-Nezami, H., Cai, Z., Lu, A., Fang, X., Jia, W., & Bian, Z.
Affiliations
  • Hong Kong Baptist University (HK)
  • Guangdong Provincial Hospital of Chinese Medicine (CN)
  • Shanghai Jiao Tong University (CN)
  • Shenzhen University (CN)
  • Guangzhou University of Chinese Medicine (CN)
  • BGI Genomics (CN)
  • University of Hong Kong (HK)
Corresponding author
  • Fang, Xiaodong
  • Jia, Wei
  • Bian, Zhaoxiang
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2019-12-09
Volume
130
Issue
1
Pages
438-450
ISSN
  • 0021-9738 (ISSN-L)
  • 1558-8238
DOI
10.1172/jci130976
PMC
PMC6934182
OpenAlex
W2993103758
Cited by
202
References
12
Citations by year
2026: 39 · 2025: 29 · 2024: 29 · 2023: 36 · 2022: 34 · 2021: 19 · 2020: 15 · 2019: 1
FWCI
5.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Investigation (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • the Innovation and Technology Fund, HKSAR (ITS-148-14FP)
  • Guangdong-Hong Kong Technology Cooperation Funding Scheme (2016A050503039)
  • Guangzhou Science and Technology Program Key Projects (201604020005)
  • Shenzhen Science and Technology Innovation Committee Grant (JCYJ20160331190123578, JCYJ20170413170320959)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Keywords
diarrhea-predominant irritable bowel syndrome, bile acids, Clostridia, Clostridium scindens, gut dysbiosis, bile acid metabolism, 7α-hydroxy-4-cholesten-3-one, FGF19, bile acid conjugates, vancomycin, fecal microbiota transplantation, gut microbiota
MeSH terms
Gastrointestinal Microbiome, Adolescent, Adult, Aged, Bile Acids and Salts, Clostridium, Diarrhea, Female, Humans, Male, Middle Aged, Irritable Bowel Syndrome

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