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Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon
Author(s) -
Chapkin Robert S.,
Davidson Laurie A.,
Park Hyejin,
Jin UnHo,
Fan YangYi,
Cheng Yating,
Hensel Martha E.,
Landrock Kerstin K.,
Allred Clinton,
Me Rani,
Klemashevich Cory,
Jayaraman Arul,
Safe Stephen
Publication year - 2021
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202100539
Subject(s) - aryl hydrocarbon receptor , lgr5 , stem cell , barrier function , chemistry , villin , organoid , receptor , microbiology and biotechnology , biology , biochemistry , cancer stem cell , gene , transcription factor , actin
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 (AhR f/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‐β1 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.