Commensal bacteria regulate vitamin A metabolism in the gut and limit pathogen burden via IL-22 modulation

Vitamin A is a key food-derived nutrient that has sweeping effects on immunity, yet, we barely understand how vitamin A uptake, metabolism and storage are regulated in the gut. Here we show that commensal bacteria play a central role in modulating vitamin A metabolism by downregulating a key metabolic gene, retinol dehydrogenase 7 (rdh7), in the intestinal epithelium. Deletion of rdh7 in intestinal epithelium resulted in lower levels of vitamin A metabolite retinoic acid (RA) coupled with reduction in RA dependent signaling in immune cells. Specifically, intestinal epithelium intrinsic RA synthesis regulated IL-22 expression as well as numbers of IL-22 producing cells. IL-22 associated antimicrobial response in the gut were also shown to be affected. Together, our findings reveal a novel role of commensal bacteria in modulating vitamin A dependent immunity and maintaining immune homeostasis.