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

TitleA Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome
Authors
Issue Date14-Jan-2020
PublisherAmerican Society for Clinical Investigation
Citation
Journal of Clinical Investigation, 2020, v. 130, n. 1, p. 438-450 How to Cite?
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.


Persistent Identifierhttp://hdl.handle.net/10722/337199
ISSN
2023 Impact Factor: 13.3
2023 SCImago Journal Rankings: 4.833
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhao, L-
dc.contributor.authorYang, W-
dc.contributor.authorChen, Y-
dc.contributor.authorHuang, FJ-
dc.contributor.authorLu, L-
dc.contributor.authorLin, CY-
dc.contributor.authorHuang, T-
dc.contributor.authorNing, ZW-
dc.contributor.authorZhai, LX-
dc.contributor.authorZhong, LLD-
dc.contributor.authorLam, WC-
dc.contributor.authorYang, Z-
dc.contributor.authorZhang, X-
dc.contributor.authorCheng, C-
dc.contributor.authorHan, LJ-
dc.contributor.authorQiu, QW-
dc.contributor.authorShang, XX-
dc.contributor.authorHuang, RY-
dc.contributor.authorXiao, HT-
dc.contributor.authorRen, ZX-
dc.contributor.authorChen, DF-
dc.contributor.authorSun, SL-
dc.contributor.authorEl-Nezami, H-
dc.contributor.authorCai, ZW-
dc.contributor.authorLu, AP-
dc.contributor.authorFang, XD-
dc.contributor.authorJia, W-
dc.contributor.authorBian, ZX-
dc.date.accessioned2024-03-11T10:18:51Z-
dc.date.available2024-03-11T10:18:51Z-
dc.date.issued2020-01-14-
dc.identifier.citationJournal of Clinical Investigation, 2020, v. 130, n. 1, p. 438-450-
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/10722/337199-
dc.description.abstract<p>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.</p>-
dc.languageeng-
dc.publisherAmerican Society for Clinical Investigation-
dc.relation.ispartofJournal of Clinical Investigation-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleA Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome-
dc.typeArticle-
dc.identifier.doi10.1172/JCI130976-
dc.identifier.scopuseid_2-s2.0-85077401822-
dc.identifier.volume130-
dc.identifier.issue1-
dc.identifier.spage438-
dc.identifier.epage450-
dc.identifier.eissn1558-8238-
dc.identifier.isiWOS:000505205000043-
dc.identifier.issnl0021-9738-

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