Vitamin D, vitamin D receptor gene polymorphisms, and inflammatory bowel disease outcomes: From molecular mechanisms to clinical application

Figure 1 Vitamin D metabolism. Endogenous vitamin D synthesis occurs in cutaneous keratinocytes under ultraviolet B rays exposure, which converts 7-dehydrocholesterol into previtamin D₃. Dietary contribution is relatively limited, derived mainly from fatty fish, dairy products, eggs, and sun-exposed mushrooms, with the absorption of vitamin D₂/D₃ occurring in the jejunum and ileum. Following synthesis or ingestion, cholecalciferol undergoes hepatic hydroxylation, generating 25-hydroxyvitamin D, and subsequently in the kidneys, producing 1,25-dihydroxyvitamin D (or calcitriol), its biologically active form. Calcitriol binds to the vitamin D receptor, which heterodimerizes with the retinoid X receptor. This complex associates with the vitamin D response element and translocates into the cell nucleus, where it regulates the expression of multiple genes involved in calcium and phosphorus metabolism, as well as in the modulation of innate and adaptive immunity. This figure was created by the authors using BioRender (Supplementary material). UVB: Ultraviolet B rays; 25(OH)D: 25-hydroxyvitamin D; 1,25(OH)₂D: 1,25-dihydroxyvitamin D; VDRE: Vitamin D response element.