Simple Analysis of Primary and Secondary Bile Salt Hydrolysis in Mouse and Human Gut Microbiome Samples by Using Fluorogenic Substrates

Chembiochem. 2020 Dec 11;21(24):3539-3543. doi: 10.1002/cbic.202000370. Epub 2020 Oct 7.

Abstract

Animals produce bile to act as an antibacterial agent and to maximize the absorption of lipophilic nutrients in the gut. The physical properties of bile are largely dictated by amphipathic bile salt molecules, which also participate in signaling pathways by modulating physiological processes upon binding host receptors. Upon excretion of bile salts from the gall bladder into the intestine, the gut microbiota can create metabolites with modified signaling capabilities. The category and magnitude of bile salt metabolism can have positive or negative effects on the host. A key modification is bile salt hydrolysis, which is a prerequisite for all additional microbial transformations. We have synthesized five different fluorogenic bile salts for simple and continuous reporting of hydrolysis in both murine and human fecal samples. Our data demonstrate that most gut microbiomes have the highest capacity for hydrolysis of host-produced primary bile salts, but some microbially modified secondary bile salts also display significant turnover.

Keywords: bile; chemical biology; fluorescence; gut microbiome; metabolism.

Publication types

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

MeSH terms

  • Animals
  • Bile Acids and Salts / chemical synthesis
  • Bile Acids and Salts / chemistry
  • Bile Acids and Salts / metabolism*
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism*
  • Gastrointestinal Microbiome
  • Humans
  • Hydrolysis
  • Mice
  • Molecular Conformation

Substances

  • Bile Acids and Salts
  • Fluorescent Dyes