Microbial Metabolites Orchestrate a Distinct Multi-Tiered Regulatory Network in the Intestinal Epithelium That Directs P-Glycoprotein Expression.

ABSTRACT: P-glycoprotein (P-gp) is a key component of the intestinal epithelium playing a pivotal role in removal of toxins and efflux of endocannabinoids to prevent excessive inflammation and sustain homeostasis. Recent studies revealed butyrate and secondary bile acids, produced by the intestinal microbiome, potentiate the induction of functional P-gp expression. We now aim to determine the molecular mechanism by which this functional microbiome output regulates P-gp. RNA sequencing of intestinal epithelial cells responding to butyrate and secondary bile acids in combination discovered a unique transcriptional program involving multiple pathways that converge on P-gp induction. Using shRNA knockdown and CRISPR/Cas9 knockout cell lines, as well as mouse models, we confirmed the RNA sequencing findi

SUBMITTER: Foley SE 

PROVIDER: S-EPMC9426490 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature