Probiotics and the BSH-related cholesterol lowering mechanism: a Jekyll and Hyde scenario
Abstract
Probiotic microorganisms have been documented over the past two decades to play a role in cholesterol-lowering properties via various clinical trials. Several mechanisms have also been proposed and the ability of these microorganisms to deconjugate bile via production of bile salt hydrolase (BSH) has been widely associated with their cholesterol lowering potentials in prevention of hypercholesterolemia. Deconjugated bile salts are more hydrophobic than their conjugated counterparts, thus are less reabsorbed through the intestines resulting in higher excretion into the feces. Replacement of new bile salts from cholesterol as a precursor subsequently leads to decreased serum cholesterol levels. However, some controversies have risen attributed to the activities of deconjugated bile acids that repress the synthesis of bile acids from cholesterol. Deconjugated bile acids have higher binding affinity towards some orphan nuclear receptors namely the farsenoid X receptor (FXR), leading to a suppressed transcription of the enzyme cholesterol 7-alpha hydroxylase (7AH), which is responsible in bile acid synthesis from cholesterol. This notion was further corroborated by our current docking data, which indicated that deconjugated bile acids have higher propensities to bind with the FXR receptor as compared to conjugated bile acids. Bile acids-activated FXR also induces transcription of the IBABP gene, leading to enhanced recycling of bile acids from the intestine back to the liver, which subsequently reduces the need for new bile formation from cholesterol. Possible detrimental effects due to increased deconjugation of bile salts such as malabsorption of lipids, colon carcinogenesis, gallstones formation and altered gut microbial populations, which contribute to other varying gut diseases, were also included in this review. Our current findings and review substantiate the need to look beyond BSH deconjugation as a single factor/mechanism in strain selection for hypercholesterolemia, and/or as a sole mean to justify a cholesterol-lowering property of probiotic strains.
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BSH activity has been implicated in the regulation of host cholesterol levels, contributing to a potential cholesterol-lowering effect.
“Among its metabolic benefits, BSH activity has been implicated in the regulation of host cholesterol levels, contributing to its potential cholesterol-lowering effect [11–13].”
From Bile Salt Hydrolase Activity in the Food-Derived Strain Levilactobacillus brevis M3R3: Genomic and Functional Characterization (2026) · cites this paper as [12]
In probiotics with typical BSH activity, the cholesterol-lowering process is likely related to the deconjugation of conjugated BAs.
“In the case of probiotics with typical BSH activity, the process is likely related to the deconjugation of conjugated BAs.32,33”
From <i>Lactiplantibacillus plantarum</i> strains KABP011, KABP012, and KABP013 modulate bile acids and cholesterol metabolism in humans (2024) · cites this paper as [33]
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“32,33 However, the precise mechanisms at play needed to be proved in humans where the relationship between probiotics, BA metabolism, and LDL profile was poorly addressed.”
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- Authors
- Choi, S.-B., Lew, L.-C., Yeo, S.-K., Nair Parvathy, S., & Liong, M.-T.
- Affiliations
- Universiti Sains Malaysia (MY)
- Taylor's University (MY)
- Corresponding author
- Liong, Min-Tze
- Venue
- Critical Reviews in Biotechnology
- Publisher
- Informa UK Limited
- Published
- 2014-02-27
- Volume
- 35
- Issue
- 3
- Pages
- 392-401
- ISSN
- 0738-8551 (ISSN-L)
- 1549-7801
- OpenAlex
- W2024812562
- Cited by
- 119
- References
- 52
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 14 · 2023: 13 · 2022: 13 · 2021: 12 · 2020: 8 · 2019: 8 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 3 · 2014: 5
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Critical Reviews in Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- probiotics, bile salt hydrolase, cholesterol lowering, bile acid deconjugation, hypercholesterolemia, farnesoid X receptor, CYP7A1, molecular docking, fat malabsorption, gallstones, gut microbiota, probiotic strain selection
- MeSH terms
- Amidohydrolases, Animals, Cholesterol, Humans, Probiotics, Mice, Microbiota
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