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Mechanism of Growth Inhibition by Free Bile Acids in Lactobacilli and Bifidobacteria
Open accessAbstract
The effects of the free bile acids (FBAs) cholic acid (CA), deoxycholic acid (DCA), and chenodeoxycholic acid on the bioenergetics and growth of lactobacilli and bifidobacteria were investigated. It was found that these FBAs reduced the internal pH levels of these bacteria with rapid and stepwise kinetics and, at certain concentrations, dissipated DeltapH. The bile acid concentrations that dissipated DeltapH corresponded with the MICs for the selected bacteria. Unlike acetate, propionate, and butyrate, FBAs dissipated the transmembrane electrical potential (DeltaPsi). In Bifidobacterium breve JCM 1192, the synthetic proton conductor pentachlorophenol (PCP) dissipated DeltapH with a slow and continuous kinetics at a much lower concentration than FBAs did, suggesting the difference in mode of action between FBAs and true proton conductors. Membrane damage assessed by the fluorescence method and a viability decrease were also observed upon exposure to CA or DCA at the MIC but not to PCP or a short-chain fatty acid mixture. Loss of potassium ion was observed at CA concentrations more than 2 mM (0.4x MIC), while leakage of other cellular components increased at CA concentrations more than 4 mM (0.8 x MIC). Additionally, in experiments with membrane phospholipid vesicles extracted from Lactobacillus salivarius subsp. salicinius JCM 1044, CA and DCA at the MIC collapsed the DeltapH with concomitant leakage of intravesicular fluorescent pH probe, while they did not show proton conductance at a lower concentration range (e.g., 0.2x MIC). Taking these observations together, we conclude that FBAs at the MIC disturb membrane integrity and that this effect can lead to leakage of proton (membrane DeltapH and DeltaPsi dissipation), potassium ion, and other cellular components and eventually cell death.
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“Some BAs serve as substrates for gut microbes, while others exhibit antimicrobial properties, actively shaping the GM at the highest taxonomic levels (318).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [318]
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Metadata
- Authors
- Kurdi, P., Kawanishi, K., Mizutani, K., & Yokota, A.
- Affiliations
- Hokkaido University (JP)
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2006-03
- Volume
- 188
- Issue
- 5
- Pages
- 1979-1986
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC1426545
- OpenAlex
- W2079166934
- Cited by
- 364
- References
- 19
- Citations by year
- 2026: 15 · 2025: 27 · 2024: 33 · 2023: 40 · 2022: 37 · 2021: 25 · 2020: 34 · 2019: 17 · 2018: 28 · 2017: 30 · 2016: 12 · 2015: 10 · 2014: 10 · 2013: 10 · 2012: 14
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Bacteriology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (submittedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- free bile acids, cholic acid, deoxycholic acid, chenodeoxycholic acid, lactobacilli, Bifidobacterium, Bifidobacterium breve, Lactobacillus salivarius, growth inhibition, membrane potential dissipation, internal pH, pentachlorophenol, membrane integrity, potassium leakage, cell death, short-chain fatty acids, minimum inhibitory concentration
- MeSH terms
- Bifidobacterium, Bile Acids and Salts, Cell Membrane, Chenodeoxycholic Acid, Deoxycholic Acid, Hydrogen-Ion Concentration, Lactobacillus, Membrane Potentials, Microbial Sensitivity Tests, Cholic Acid
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