Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon. Academic Article uri icon


  • 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 dextran sodium sulfate (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 are 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 inhibit DSS-induced damage to intestinal barrier function and DSS-induced mucosal inflammatory genes such as IL-6 and TGF-1 in wild-type (AhR+/+ ) but not AhR-/- mice. In contrast, coffee does 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.

published proceedings

  • Mol Nutr Food Res

altmetric score

  • 0.5

author list (cited authors)

  • Chapkin, R. S., Davidson, L. A., Park, H., Jin, U., Fan, Y., Cheng, Y., ... Safe, S.

citation count

  • 2

complete list of authors

  • Chapkin, Robert S||Davidson, Laurie A||Park, Hyejin||Jin, Un-Ho||Fan, Yang-Yi||Cheng, Yating||Hensel, Martha E||Landrock, Kerstin K||Allred, Clinton||Menon, Rani||Klemashevich, Cory||Jayaraman, Arul||Safe, Stephen

publication date

  • October 2021