Bile salt biotransformations by human intestinal bacteria

Ridlon, Jason M.; Kang, Dae-Joong; Hylemon, Phillip B.

doi:10.1194/jlr.r500013-jlr200

Cited by 2,829Gut microbiota and healthSteroid Chemistry and BiochemistryDrug Transport and Resistance Mechanisms

Bile salt biotransformations by human intestinal bacteria

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Ridlon, Jason M., Kang, Dae-Joong, Hylemon, Phillip B.·2006·Journal of Lipid Research

DOI 10.1194/jlr.r500013-jlr200

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Abstract

Secondary bile acids, produced solely by intestinal bacteria, can accumulate to high levels in the enterohepatic circulation of some individuals and may contribute to the pathogenesis of colon cancer, gallstones, and other gastrointestinal (GI) diseases. Bile salt hydrolysis and hydroxy group dehydrogenation reactions are carried out by a broad spectrum of intestinal anaerobic bacteria, whereas bile acid 7-dehydroxylation appears restricted to a limited number of intestinal anaerobes representing a small fraction of the total colonic flora. Microbial enzymes modifying bile salts differ between species with respect to pH optima, enzyme kinetics, substrate specificity, cellular location, and possibly physiological function. Crystallization, site-directed mutagenesis, and comparisons of protein secondary structure have provided insight into the mechanisms of several bile acid-biotransforming enzymatic reactions. Molecular cloning of genes encoding bile salt-modifying enzymes has facilitated the understanding of the genetic organization of these pathways and is a means of developing probes for the detection of bile salt-modifying bacteria. The potential exists for altering the bile acid pool by targeting key enzymes in the 7alpha/beta-dehydroxylation pathway through the development of pharmaceuticals or sequestering bile acids biologically in probiotic bacteria, which may result in their effective removal from the host after excretion.

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BSHs deconjugate primary conjugated bile acids such as TCA and GCA to generate cholic acid (CA).
“Primary conjugated BAs synthesized in the liver, such as the tauro- and glycoconjugates of cholic acid (TCA, GCA), are deconjugated by BSHs to generate cholic acid (CA)”
From Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut (2023) · cites this paper as [11]
The vanguard deconjugation reaction acts as a gatekeeper for subsequent BA transformations that turn primary BAs into secondary BAs.
“This vanguard reaction acts as a ‘gatekeeper’ for subsequent BA transformations that turn primary BAs into secondary BAs”
From Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut (2023) · cites this paper as [11]
There is an intensive bidirectional interaction between bile acids and intestinal microbiota.
“There is an intensive bidirectional interaction between BAs and intestinal microbiota.51”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [51]
Primary bile acids are converted to secondary bile acids by the local microbiota, partly in the small intestine and predominantly in the colon, beginning with deconjugation and followed by dehydroxylation.
“Primary bile acids are converted to secondary bile acids by the local microbiota, partly in the small intestine and predominantly in the colon. This involves multiple steps and typically begins with the initial deconjugation of glycine or taurine, followed by dehydroxylation (Ridlon et al., 2006).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Ridlon et al., 2006
Bile acid activity of commensal bacteria is involved in a complex interplay with host hepatic enzymes, and together they promote digestion and absorption of dietary lipids.
“Bile acid activity of commensal bacteria is involved in a complex interplay with host hepatic enzymes, and together they promote digestion and absorption of dietary lipids.42”
From The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids (2015) · cites this paper as [42]

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Diet rapidly and reproducibly alters the human gut microbiome
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“BSH genes have been detected in the main bacterial genera of the gut microbiota [32] and the enzyme has been purified from Bacteroides fragilis, B. vulgatus, Clostridium perfringens, Listeria monocytogenes and several species of Lactobacillus and Bifidobacterium.”
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Authors: Ridlon, J. M., Kang, D.-J., & Hylemon, P. B.
Affiliations: Virginia Commonwealth University (US)
ORCID: Ridlon, Jason M.
Hylemon, Phillip B.
Venue: Journal of Lipid Research
Publisher: Elsevier BV
Published: 2006-02
Volume: 47
Issue: 2
Pages: 241-259
ISSN: 0022-2275 (ISSN-L)
DOI: 10.1194/jlr.r500013-jlr200
OpenAlex: W2071273298
Cited by: 2,829
References: 178
Citations by year: 2026: 202 · 2025: 220 · 2024: 211 · 2023: 245 · 2022: 263 · 2021: 252 · 2020: 238 · 2019: 200 · 2018: 191 · 2017: 161 · 2016: 130 · 2015: 119 · 2014: 87 · 2013: 91 · 2012: 51
FWCI: 1.11
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 5326 d)
Locations: Journal of Lipid Research (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (P01DK038030, P01 DK 38030)
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: secondary bile acids, enterohepatic circulation, enzyme kinetics, enzyme structure, gene cloning, probiotics, bile acid sequestration, colon cancer, gallstones
MeSH terms: Amidohydrolases, Amino Acid Sequence, Bacteria, Bile Acids and Salts, Biotransformation, Cholic Acids, Colonic Neoplasms, Humans, Hydrogen Sulfide, Hydroxysteroid Dehydrogenases, Intestinal Mucosa, Intestines, Models, Molecular, Molecular Sequence Data, Taurine, Molecular Structure, Sequence Homology, Amino Acid

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Bile salt biotransformations by human intestinal bacteria

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