Continuum of Host-Gut Microbial Co-metabolism: Host CYP3A4/3A7 are Responsible for Tertiary Oxidations of Deoxycholate Species.

ABSTRACT: The gut microbiota modifies endogenous primary bile acids (BAs) to produce exogenous secondary BAs, which may be further metabolized by cytochrome P450 enzymes (P450s). Our primary aim was to examine how the host adapts to the stress of microbe-derived secondary BAs by P450-mediated oxidative modifications on the steroid nucleus. Five unconjugated tri-hydroxyl BAs that were structurally and/or biologically associated with deoxycholate (DCA) were determined in human biologic samples by liquid chromatography-tandem mass spectrometry in combination with enzyme-digestion techniques. They were identified as DCA-19-ol, DCA-6β-ol, DCA-5β-ol, DCA-6α-ol, DCA-1β-ol, and DCA-4β-ol based on matching in-laboratory synthesized standards. Metabolic inhibition assays in

SUBMITTER: Zhang J 

PROVIDER: S-EPMC6378331 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature