Targeting the Aryl Hydrocarbon Receptor in Stem Cells to Improve the Use of Food as Medicine

Purpose of Review: Intestinal stem cells, the most rapidly proliferating adult stem cells, are exquisitely sensitive to extrinsic dietary factors. Uncontrolled regulation of intestinal stem cells is closely linked to colon tumorigenesis. This review focuses on how dietary- and microbial-derived cues regulate intestinal stem cell functionality and colon tumorigenesis in mouse models by targeting the aryl hydrocarbon receptor (AhR). Recent Findings: AhR, a ligand-activated transcription factor, can integrate environmental, dietary, and microbial cues to modulate intestinal stem cell proliferation, differentiation, and their microenvironment, affecting colon cancer risk. Modulation of AhR activity is associated with many chronic diseases, including inflammatory bowel diseases where AhR expression is protective. Summary: AhR signaling controls the maintenance and differentiation of intestinal stem cells, influences local niche factors, and plays a protective role in colon tumorigenesis. Mounting evidence suggests that extrinsic nutritional/dietary cues which modulate AhR signaling may be a promising approach to colon cancer chemoprevention.