Lactobacillus bile salt hydrolase substrate specificity governs bacterial fitness and host colonization
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Significance: The transformation of bile acids (BAs) by the gut microbiota is increasingly recognized as an important factor shaping host health. The prerequisite step of BA metabolism is carried out by bile salt hydrolases (BSHs), which are encoded by select gut and probiotic bacteria. Despite their prevalence, the utility of harboring a bsh is unclear. Here, we investigate the role of BSHs encoded by Lactobacillus acidophilus and Lactobacillus gasseri . We show that BA type and BSH substrate preferences affect in vitro and in vivo growth of both species. These findings contribute to a mechanistic understanding of bacterial survival in various BA-rich niches and inform future efforts to leverage BSHs as a therapeutic tool for manipulating the gut microbiota.
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Certain deconjugated bile salts can exert more toxic effects on bacterial cells than their conjugated counterparts.
“a recent study revealed that, contrary to the earlier assumptions, certain deconjugated BSs can exert more toxic effects on bacterial cells than their conjugated counterparts [73].”
From Bile Salt Hydrolase Activity in the Food-Derived Strain Levilactobacillus brevis M3R3: Genomic and Functional Characterization (2026) · cites this paper as [73]
Exposure to bile does not necessarily induce bsh gene expression in BSH-active lactobacilli strains.
“This result is also consistent with previous works indicating that exposure to bile does not necessarily induce bsh gene expression in BSH-active lactobacilli strains [73, 86].”
From Bile Salt Hydrolase Activity in the Food-Derived Strain Levilactobacillus brevis M3R3: Genomic and Functional Characterization (2026) · cites this paper as [73]
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Functional and Phylogenetic Diversity of BSH and PVA Enzymes
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“Consistently, a recent study revealed that, contrary to the earlier assumptions, certain deconjugated BSs can exert more toxic effects on bacterial cells than their conjugated counterparts [73].”
- Authors
- Foley, M. H., O’Flaherty, S., Allen, G., Rivera, A. J., Stewart, A. K., Barrangou, R., & Theriot, C. M.
- Affiliations
- North Carolina State University (US)
- Corresponding author
- Barrangou, Rodolphe
- Theriot, Casey M.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2021-02
- Volume
- 118
- Issue
- 6
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC8017965
- OpenAlex
- W3128625686
- Cited by
- 205
- References
- 90
- Citations by year
- 2026: 49 · 2025: 38 · 2024: 29 · 2023: 40 · 2022: 32 · 2021: 17
- FWCI
- 9.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Office of Extramural Research, National Institutes of Health (T32DK07737, P30DK034987)
- DuPont (BSH)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- bile salt hydrolase, Lactobacillus acidophilus, Lactobacillus gasseri, bile acid metabolism, substrate specificity, bacterial fitness, host colonization, gut microbiota, probiotics
- MeSH terms
- Gastrointestinal Microbiome, Amidohydrolases, Humans, Lactobacillus, Substrate Specificity, Ecosystem, Probiotics, Host-Pathogen Interactions, Genetic Fitness
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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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