A biosynthetic pathway for a prominent class of microbiota-derived bile acids
Open accessAbstract
The gut bile acid pool is millimolar in concentration, varies widely in composition among individuals and is linked to metabolic disease and cancer. Although these molecules are derived almost exclusively from the microbiota, remarkably little is known about which bacterial species and genes are responsible for their biosynthesis. Here we report a biosynthetic pathway for the second most abundant class in the gut, 3β-hydroxy(iso)-bile acids, whose levels exceed 300 μM in some humans and are absent in others. We show, for the first time, that iso-bile acids are produced by Ruminococcus gnavus, a far more abundant commensal than previously known producers, and that the iso-bile acid pathway detoxifies deoxycholic acid and thus favors the growth of the keystone genus Bacteroides. By revealing the biosynthetic genes for an abundant class of bile acids, our work sets the stage for predicting and rationally altering the composition of the bile acid pool.
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Previous research highlighted the involvement of R. gnavus in bile acid metabolism, particularly the production of iso-bile acids, which were elevated in Japanese centenarians.
“Previous research also highlighted the involvement of R. gnavus in bile acid metabolism, 44 particularly the production of iso-bile acids, which were elevated in Japanese centenarians. 45”
From Global genetic diversity of human gut microbiome species is related to geographic location and host health (2025) · cites this paper as [44]
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- Authors
- Devlin, A. S., & Fischbach, M. A.
- Affiliations
- QB3 (US)
- Corresponding author
- Fischbach, Michael A
- Venue
- Nature Chemical Biology
- Published
- 2015-07-20
- Volume
- 11
- Issue
- 9
- Pages
- 685-690
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC4543561
- OpenAlex
- W958079127
- Cited by
- 448
- References
- 48
- Citations by year
- 2026: 47 · 2025: 47 · 2024: 50 · 2023: 50 · 2022: 71 · 2021: 40 · 2020: 36 · 2019: 31 · 2018: 32 · 2017: 19 · 2016: 21 · 2015: 3 · 2014: 1
- FWCI
- 10.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (1dp2od007290-01)
- National Institute of General Medical Sciences (P50GM081879, GM081879)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- bile acid synthesis, deoxycholic acid, Ruminococcus gnavus, Bacteroides, gut microbiota, bile acid detoxification, biosynthetic enzymes
- MeSH terms
- Bacterial Proteins, Bacteroides, Bile Acids and Salts, Escherichia coli, Humans, Kinetics, Microbial Sensitivity Tests, NAD, NADP, Recombinant Proteins, Stereoisomerism, Symbiosis, Gene Expression, 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific), Ruminococcus, Microbiota
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