VitaminD: A Critical Regulator of Intestinal Physiology

Abstract

Calcium is required for the functioning of numerous biological processes and is essential for skeletal health. The major source of new calcium is from the diet. The central role of vitamin D in the maintenance of calcium homeostasis is to increase the absorption of ingested calcium from the intestine. The critical importance of vitamin D in this process is noted in the causal link between vitamin D deficiency and rickets as well as in studies using genetically modified mice including mice deficient in the vitamin D receptor (Vdr null mice) or in the cytochrome P-450 enzyme, 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1) that converts 25-hydroxyvitamin D3 to the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (Cyp27b1 null mice). When these mice are fed diets with high calcium and lactose rickets is prevented. The studies in the mouse models provide supporting evidence indicating that the major physiological function of 1,25(OH)2D3/VDR is intestinal calcium absorption. This review summarizes what is known about mechanisms involved in vitamin D regulated intestinal calcium absorption. Recent studies suggest that vitamin D does not affect a single entity but that a complex network of calcium regulating components is involved in the process of 1,25(OH)2D3 mediated active intestinal calcium absorption. In addition, numerous 1,25(OH)2D3 actions in the intestine have been described independent of calcium absorption. Although the translatability to humans requires further definition, an overview is presented related to compelling evidence from the laboratory of 1,25(OH)2D3 intestinal effects which include regulation of adhesion molecules to enhance barrier function, regulation of intestinal stem cell function, cellular homeostasis of other divalent cations, regulation of drug metabolizing enzymes and anti-inflammatory effects.

Genomic analysis of 1,25-dihydroxyvitamin D3 action in mouse intestine reveals compartment and segment-specific gene regulatory effects

“…DESeq2 was then used to generate FPKM values per kilobase of gene length per million mapped fragments in each tissue sample with comparison of vitamin D–deficient replicates with 3 x D treated replicates. Two kinds of data were outputted from DESeq2: ( 1 ) a results table for reporting mean of normalized counts for all samples and through comparison of the treated condition versus untreated condition, log2 fold change, standard error, Wald statistic, Wald test p -value, and Benjamini-Hochberg adjusted p -value and ( 2 ) an FPKM table output of fragment counts normalized per kilobase of feature length per million mapped fragments.…”

“…Vitamin D is an important nutrient with critical regulatory actions on intestinal physiology and function ( 1 ). Vitamin D is metabolized to become 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), a hormone that activates the vitamin D receptor (VDR) to mediate the transcription of target genes.…”

“…In addition to maintenance of calcium homeostasis, many other beneficial intestinal effects of 1,25(OH) 2 D 3 have been described including anti-inflammatory effects, maintenance of intestinal barrier function, and protection against colitis and colon cancer, suggesting the existence of multiple, diverse 1,25(OH) 2 D 3 functions across the length of the intestine ( 1 ). In addition to functional differences that exist along the proximal-to-distal axis, the proximal segments of the intestine have epithelial cells organized along a crypt–villus axis.…”

Calcifediol (25OH Vitamin D3) Deficiency: A Risk Factor from Early to Old Age

“…The action of vitamin D-calcifediol-1,25(OH) 2 D on the intestine is mainly the stimulation of calcium transport by regulating a number of genes such as TRPV6 at the mucosal membrane, intracellular calcium binding proteins (such as calbindin 9k), or serosal calcium transporters. In addition, the VDR endocrine system regulates tight junction genes (such as claudins) thereby mediating paracellular calcium transport [ 19 , 20 ].…”

Vitamin D3 Metabolic Enzymes in Plateau Zokor (Myospalax baileyi) and Plateau Pika (Ochotona curzoniae): Expression and Response to Hypoxia

“…Vitamin D 3 is a fat-soluble secosteroid that has a fundamental role in the maintenance of calcium and phosphate homeostasis [ 1 , 2 , 3 , 4 , 5 ]. Vitamin D 3 has a variety of pleiotropic functions in many extra-skeletal targets [ 2 ].…”