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

Brian V Jones, Máire Begley, Colin Hill, Cormac G M Gahan, Julian R Marchesi

Research output: Contribution to journalArticle

412 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13580-5
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number36
Early online date29 Aug 2008
DOIs
Publication statusPublished - 9 Sep 2008

Keywords

  • Amidohydrolases/genetics
  • Amino Acid Sequence
  • Evolution, Molecular
  • Gastrointestinal Tract/enzymology
  • Humans
  • Metagenome/genetics
  • Methanobrevibacter/enzymology
  • Phylogeny

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