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A selective gut bacterial bile salt hydrolase alters host metabolism
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The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-β-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.
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“B. Dorei possesses high BSH activity in vitro (Yao et al., 2018)”
From Bacteroides dorei BDX-01 alleviates DSS-induced experimental colitis in mice by regulating intestinal bile salt hydrolase activity and the FXR-NLRP3 signaling pathway (2023) · cites this paper as Yao et al., 2018
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Metadata
- Authors
- Yao, L., Seaton, S. C., Ndousse-Fetter, S., Adhikari, A. A., DiBenedetto, N., Mina, A. I., Banks, A. S., Bry, L., & Devlin, A. S.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Devlin, A Sloan
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-07-17
- Volume
- 7
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6078496
- OpenAlex
- W2884910880
- Cited by
- 274
- References
- 90
- Citations by year
- 2026: 28 · 2025: 33 · 2024: 41 · 2023: 28 · 2022: 45 · 2021: 41 · 2020: 32 · 2019: 23 · 2018: 3
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (P30DK034854)
- Wellington Postdoctoral Fellowship
- Massachusetts Institute of Technology (Center for Microbiome Informatics and Therapeutics – Innovation Award)
- Karin Grunebaum Cancer Research Foundation (Junior Faculty Award)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- bile salt hydrolase, Bacteroides thetaiotaomicron, gut microbiota, host metabolism, bile acids, obesity, metabolic syndrome, gnotobiotic mice, respiratory exchange ratio, circadian rhythm, immune gene expression, microbial metabolites
- MeSH terms
- Bacteroides thetaiotaomicron, Host Microbial Interactions, Amidohydrolases, Animals, Body Weight, Circadian Rhythm, Germ-Free Life, Immunity, Intestines, Liver, Metabolism, Respiration, Taurocholic Acid, Gene Expression Profiling, Gastrointestinal Tract, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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