Cited by 1,098Gut microbiota and healthSteroid Chemistry and BiochemistryDrug Transport and Resistance Mechanisms

Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome

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Jones, Brian V., Begley, Máire, Hill, Colin, Gahan, Cormac G. M., Marchesi, Julian R.·2008·Proceedings of the National Academy of Sciences

Abstract

Bile salt hydrolases (BSHs) catalyze the “gateway” reaction in a wider pathway of bile acid modification by the gut microbiota. Because bile acids function as signaling molecules regulating their own biosynthesis, lipid absorption, cholesterol homeostasis, and local mucosal defenses in the intestine, microbial BSH activity has the potential to greatly influence host physiology. However, the function, distribution, and abundance of BSH enzymes in the gut community are unknown. Here, we show that BSH activity is a conserved microbial adaptation to the human gut environment with a high level of redundancy in this ecosystem. Through metagenomic analyses we identified functional BSH in all major bacterial divisions and archaeal species in the gut and demonstrate that BSH is enriched in the human gut microbiome. Phylogenetic analysis illustrates that selective pressure in the form of conjugated bile acid has driven the evolution of members of the Ntn_CGH-like family of proteins toward BSH activity in gut-associated species. Furthermore, we demonstrate that BSH mediates bile tolerance in vitro and enhances survival in the murine gut in vivo . Overall, we demonstrate the use of function-driven metagenomics to identify functional anchors in complex microbial communities, and dissect the gut microbiome according to activities relevant to survival in the mammalian gastrointestinal tract.

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Crossref · 10.1073/pnas.0804437105

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38 of 38 references verified0 citation errors · 0 not checkable

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  • All major gut-associated bacterial divisions, including Lactobacillus, Bifidobacterium and Bacteroidetes taxa, express bile salt hydrolase (BSH) enzymes which allow de-conjugation of bile acids from taurine and glycine.

    “Strikingly, all major gut-associated bacterial divisions, including Lactobacillus, Bifidobacterium and Bacteroidetes taxa, were shown to express bile salt hydrolase (BSH) enzymes which allow de-conjugation of bile acids from taurine and glycine (Begley et al., 2006;Jones et al., 2008).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Jones et al., 2008

  • Host substrates, such as mucin and bile salts, can be metabolized by the gut microbiota.

    “Host substrates, such as mucin and bile salts, can also be metabolized by the gut microbiota [18, 19].”

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Authors
Jones, B. V., Begley, M., Hill, C., Gahan, C. G. M., & Marchesi, J. R.
Affiliations
  • University College Cork (IE)
  • Teagasc - The Irish Agriculture and Food Development Authority (IE)
  • *Alimentary Pharmabiotic Centre and Department of Microbiology, and
Venue
Proceedings of the National Academy of Sciences
Published
2008-09-09
Volume
105
Issue
36
Pages
13580-13585
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2035779227
Cited by
1,098
References
38
Citations by year
2026: 78 · 2025: 95 · 2024: 101 · 2023: 92 · 2022: 114 · 2021: 102 · 2020: 74 · 2019: 76 · 2018: 61 · 2017: 41 · 2016: 38 · 2015: 41 · 2014: 54 · 2013: 43 · 2012: 25
FWCI
8.65
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • University of Brighton Repository (University of Brighton) (submittedVersion)
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 salt hydrolase, human gut microbiome, bile acid metabolism, functional metagenomics, bile tolerance, selection pressure, bile acid conjugates, archaea, bacterial diversity, host-microbe interactions
MeSH terms
Amidohydrolases, Amino Acid Sequence, Humans, Phylogeny, Evolution, Molecular, Methanobrevibacter, Gastrointestinal Tract, Metagenome

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