Vitamin D and Microbiome Molecular Interaction in Inflammatory Bowel Disease Pathogenesis

Studies of systemic autoimmune diseases point to characteristic microbial patterns in various diseases, including inflammatory bowel disease (IBD). Autoimmune diseases, and IBD in particular, show a predisposition to vitamin D deficiency, leading to alterations in the microbiome and disruption of intestinal epithelial barrier integrity. This review examines the role of the gut microbiome in IBD and discusses how vitamin D-vitamin D receptor (VDR)-associated molecular signaling pathways contribute to the development and progression of IBD through their effects on gut barrier function, the microbial community, and immune system function. The present data demonstrate that vitamin D promotes the proper function of the innate immune system by acting as an immunomodulator, exerting anti-inflammatory effects, and critically contributing to the maintenance of gut barrier integrity and modulation of the gut microbiota, mechanisms that may influence the IBD development and pro-gression. VDR regulates the biological effects of vitamin D and is related to environmental, genetic, immunologic, and microbial aspects of IBD. Vitamin D influences the distribution of the fecal micro-biota, with high vitamin D levels associated with increased levels of beneficial bacterial species and lower levels of pathogenic bacteria. Understanding the cellular functions of vitamin D-VDR signaling in intestinal epithelial cells may pave the way for the development of new treatment strategies for the therapeutic armamentarium of IBD in the near future. (Am J Pathol 2023, 193: 656-668; https:// doi.org/10.1016/j.ajpath.2023.02.004)