Ancient Nuclear Receptor VDR With New Functions: Microbiome and Inflammation

The biological functions of 1α,25-dihydroxyvitamin D3 are regulated by nuclear receptor vitamin D receptor (VDR). The expression level of VDR is high in intestine. VDR is an essential regulator of intestinal cell proliferation, barrier function, and immunity. Vitamin D/VDR plays a protective role in inflammatory bowel diseases (IBDs), both ulcerative colitis and Crohn's disease. Emerging evidence demonstrates low VDR expression and dysfunction of vitamin D/VDR signaling in patients with IBD. Here, we summarize the progress made in vitamin D/VDR signaling in genetic regulation, immunity, and the microbiome in IBD. We cover the mechanisms of intestinal VDR in regulating inflammation through inhibiting the NF-ĸB pathway and activating autophagy. Recent studies suggest that the association of VDR single nucleotide polymorphisms with immune and intestinal pathology may be sex dependent. We emphasize the tissue specificity of VDR and its sex- and time-dependent effects. Furthermore, we discuss potential clinical application and future direction of vitamin D/VDR in preventing and treating IBD.