Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization

• DOI: 10.3390/ijms21072614
• Publication Date: 2020-04-09T18:42:03Z
• Authors: Barbora Vyhlídalová; Kristýna Krasulová; Petra Pečinková; Adéla Marcalíková; Radim Vrzal; Lenka Zemánková; Jan Vančo; Zdeněk Trávníček; Jan Vondráček; Martina Karasová; Sridhar Mani; Zdeněk Dvořák
• Keywords: Skatole; Acetamide

We examined the effects of gut microbial catabolites tryptophan on aryl hydrocarbon receptor (AhR). Using a reporter gene assay, we show that all studied are low-potency agonists human AhR. The efficacy differed substantially, comprising with no or low (i3-propionate, i3-acetate, i3-lactate, i3-aldehyde), medium (i3-ethanol, i3-acrylate, skatole, tryptamine), and high (indole, i3-acetamide, i3-pyruvate) efficacies. displayed ligand-selective antagonist activities by i3-pyruvate, i3-aldehyde, indole, tryptamine. Ligand binding assay identified affinity (skatole, i3-acetamide) very (i3-acrylate, i3-ethanol, indole) ligands murine Indole, tryptamine, i3-acetamide induced CYP1A1 mRNA in intestinal LS180 HT-29 cells, but not AhR-knockout variant. observed similar induction pattern primary hepatocytes. most AhR-active elicited nuclear translocation AhR, followed formation AhR-ARNT heterodimer enhanced AhR to promoter. Collectively, comprehensively characterized interactions which may expand current understanding their potential roles health disease.