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Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon.

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 (AhRf/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.