The endocrine vitamin D system in the gut

Abstract

The active vitamin D metabolite 1α,25-dihydroxyvitamin D (1,25(OH)D) has important regulatory actions in the gut through endocrine and probably also intracrine, autocrine and paracrine mechanisms. By activating the vitamin D receptor (VDR), which is expressed at a high level in the small intestine and colon, 1,25(OH)D regulates numerous genes that control gut physiology and homeostasis. 1,25(OH)D is a major responsible for epithelial barrier function and calcium and phosphate absorption, and the host's defense against pathogens and the inflammatory response by several types of secretory and immune cells. Moreover, recent data suggest that 1,25(OH)D has a regulatory effect on the gut microbiota and stromal fibroblasts. Many studies have linked vitamin D deficiency to inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and to an increased risk of colorectal cancer, and the possible use of VDR agonists to prevent or treat these diseases is receiving increasing interest.

Vitamin D differentially regulates colon stem cells in patient‐derived normal and tumor organoids

“…The pro‐differentiation effect of calcitriol on tumor organoid cells is in line, albeit less apparent, with that observed in colon carcinoma cell lines grown on plastic dishes . Notably, VDR agonists have been proposed to promote terminal differentiation of normal upper crypt absorptive enterocytes , which however is not observed in cells of normal colon organoids. This discrepancy may rely on differences in the microenvironment (location and other signals) and the distinct phenotype of these two cell populations (top crypt enterocytes/bottom crypt stem cells) in human tissue and organoid culture, respectively.…”

Cellular and molecular mechanisms of vitamin D in food allergy

“…Intestinal dysbiosis increases susceptibility to pathogens and toxins and triggers inflammatory responses, and it is proposed that this cascade can lead to food allergies . Studies in mice have shown a link between vitamin D deficiency, or VDR suppression, and alterations to gut microbe composition . Clostridium and Bacteroides were depleted in faeces in one study of VDR deficient mice, whereas Lactobacillus was enriched .…”

The Role of Vitamin D in the Immune System as a Pro-survival Molecule

“…154,155 Vitamin D should play a regulatory role in gut immunology, which has been recently reviewed. 57,[156][157][158] Its activity on hypersensitive reactions, and more commonly on allergy, may come from the evidence-somewhat controversialthat vitamin D deficiency, particularly in a pediatric population, would be associated with challengeproven food allergy in the first year of life. [159][160][161] This evidence was contradicted by more recent reports, however.…”