Forskning

August 19, 2021

R S Chapkin et al, 2021. Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon

R S Chapkin et al, 2021. Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon, Molecular Nutrition and Food Research, published online.

ABSTRACT:

Scope: This study investigates the mechanism of action and functional effects of coffee extracts in colonic cells, on intestinal stem cell growth and inhibition of DSS-induced intestinal barrier damage in mice.

Methods and results: Aqueous coffee extracts induced Ah receptor (AhR) -responsive CYP1A1, CYP1B1 and UGT1A1 gene expression in colon-derived Caco2 and YAMC cells. Tissue-specific AhR knockout (AhR^f/f x Lgr5-GFP-CreERT2 x Villin-Cre), wild-type (Lgr5-CreERT2 x Villin-Cre) mice were sources of stem cell enriched organoids and both coffee extracts and norharman, an AhR-active component of these extracts inhibited stem cell growth. Coffee extracts also inhibited DSS-induced damage to intestinal barrier function and DSS-induced mucosal inflammatory genes such as IL-6 and TGF-β1 in wild-type (AhR^+/+ ) but not AhR^-/- mice. In contrast, coffee did not exhibit protective effects in intestinal-specific AhR knockout mice. Coffee extracts also enhanced overall formation of AhR-active microbial metabolites.

Conclusions: In colon-derived cells and in the mouse intestine, coffee induced several AhR-dependent responses including gene expression, inhibition of intestinal stem cell-enriched organoid growth and inhibition of DSS-induced intestinal barrier damage. We conclude that the anti-inflammatory effects of coffee in the intestine are due, in part, to activation of AhR signaling. This article is protected by copyright. All rights reserved.