A selective gut bacterial bile salt hydrolase alters host metabolism

Elife. 2018 Jul 17;7:e37182. doi: 10.7554/eLife.37182.

Abstract

The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-β-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.

Keywords: bacteroides thetaiotaomicron; bile salt hydrolase; biochemistry; chemical biology; human microbiome; infectious disease; metabolism; microbiology; mouse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / genetics
  • Amidohydrolases / metabolism*
  • Animals
  • Bacteroides thetaiotaomicron / enzymology*
  • Bacteroides thetaiotaomicron / genetics
  • Bacteroides thetaiotaomicron / isolation & purification
  • Body Weight
  • Circadian Rhythm
  • Gastrointestinal Tract / microbiology*
  • Gene Expression Profiling
  • Germ-Free Life
  • Host Microbial Interactions*
  • Immunity
  • Intestines / physiology
  • Liver / physiology
  • Metabolism
  • Mice
  • Respiration
  • Taurocholic Acid / analogs & derivatives*
  • Taurocholic Acid / metabolism

Substances

  • tauromuricholic acid
  • Taurocholic Acid
  • Amidohydrolases
  • choloylglycine hydrolase