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<p>Conjugated bile acids (BAs) are multi-functional detergents in the gastrointestinal (GI) tract produced by the liver enzyme bile acid-CoA:amino acid N-acyltransferase (BAAT) and by the microbiome from the acyltransferase activity of bile salt hydrolase (BSH). Humans with inflammatory bowel disease (IBD) have an enrichment in both host and microbially conjugated BAs (MCBAs), but their impacts on GI inflammation are not well understood. We investigated the role of host-conjugated BAs in a mouse model of colitis using a <i>BAAT</i> knockout background. <i>Baat</i><sup><i>−/−</i></sup> KO mice have severe phenotypes in the colitis model that were rescued by supplementation with taurocholate (TCA). Gene expression and histology showed that this rescue was due to an improved epithelial barrier integrity and goblet cell function. However, metabolomics also showed that TCA supplementation resulted in extensive metabolism to secondary BAs. We therefore investigated the BSH activity of diverse gut bacteria on a panel of conjugated BAs and found broad hydrolytic capacity depending on the bacterium and the amino acid conjugate. The complexity of this microbial BA hydrolysis led to the exploration of <i>bsh</i> genes in metagenomic data from human IBD patients. Certain <i>bsh</i> sequences were enriched in people with Crohn’s disease particularly that from <i>Ruminococcus gnavus</i>. This study shows that both host and microbially conjugated BAs may provide benefits to those with IBD, but this is dictated by a delicate balance between BA conjugation/deconjugation based on the <i>bsh</i> genes present.</p>

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Balance between bile acid conjugation and hydrolysis activity can alter outcomes of gut inflammation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月11日

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  • Yousi Fu,
  • Douglas V. Guzior,
  • Maxwell Okros,
  • Christopher Bridges,
  • Sabrina L. Rosset,
  • Cely T. González,
  • Christian Martin,
  • Hansani Karunarathne,
  • Victoria E. Watson,
  • Robert A. Quinn

摘要

Conjugated bile acids (BAs) are multi-functional detergents in the gastrointestinal (GI) tract produced by the liver enzyme bile acid-CoA:amino acid N-acyltransferase (BAAT) and by the microbiome from the acyltransferase activity of bile salt hydrolase (BSH). Humans with inflammatory bowel disease (IBD) have an enrichment in both host and microbially conjugated BAs (MCBAs), but their impacts on GI inflammation are not well understood. We investigated the role of host-conjugated BAs in a mouse model of colitis using a BAAT knockout background. Baat−/− KO mice have severe phenotypes in the colitis model that were rescued by supplementation with taurocholate (TCA). Gene expression and histology showed that this rescue was due to an improved epithelial barrier integrity and goblet cell function. However, metabolomics also showed that TCA supplementation resulted in extensive metabolism to secondary BAs. We therefore investigated the BSH activity of diverse gut bacteria on a panel of conjugated BAs and found broad hydrolytic capacity depending on the bacterium and the amino acid conjugate. The complexity of this microbial BA hydrolysis led to the exploration of bsh genes in metagenomic data from human IBD patients. Certain bsh sequences were enriched in people with Crohn’s disease particularly that from Ruminococcus gnavus. This study shows that both host and microbially conjugated BAs may provide benefits to those with IBD, but this is dictated by a delicate balance between BA conjugation/deconjugation based on the bsh genes present.