Vitamin D in Inflammatory Bowel Diseases. Mechanisms of Action and Therapeutic Implications

Abstract

(1) Background: Vitamin D is an immunoregulatory factor influencing intestinal homeostasis. Recent evidence supports a central role of this micronutrient in the course of Inflammatory Bowel Diseases (IBD). This narrative review aims to provide a general overview of the possible biological mechanisms of action of vitamin D and its therapeutic implications in IBD. (2) Methods: A systematic electronic search of the English literature up to October 2021 was performed using Medline and the Cochrane Library. Only papers written in English that analyzed the role of vitamin D in IBD were included. (3) Results: In vitro and animal studies reported that vitamin D signaling improves epithelial barrier integrity regulating the expression of several junctional proteins, defensins, and mucins, modulates the inflammatory response, and affects gut microbiome composition. Recent studies also suggest that vitamin D deficiency is highly prevalent among IBD patients and that low serum levels correlate with disease activity and, less clearly, with disease course. (4) Conclusions: An increasing body of evidence suggests some role of vitamin D in the pathophysiology of IBD, nonetheless the underlying mechanisms have been so far only partially elucidated. A strong correlation with disease activity has been reported but its implication in the treatment is still undefined. Thus, studies focused on this issue, the definition of vitamin D levels responsible for clinical effects, and the potential role of vitamin D as a therapeutic agent are strongly encouraged.

Keywords: Crohn’s disease; IBD; inflammation; micronutrient; ulcerative colitis.

Figure 1

Vitamin D is synthesized in the skin in response to ultraviolet light or provided by the diet. It is first converted to 25-hydroxyvitamin D3 by hydroxylation occurring in the liver and then further converted into its active metabolite, 1,25-dihydroxyvitamin D3, in the kidney. Ca = calcium; P = phosphate; CYP2R1 = Cytochrome P450 Family 2 Subfamily R Member 1; CYP27B1= Cytochrome P450 Family 27 Subfamily B Member 1; 25(OH) vitamin D = 25-hydroxyvitamin D; 1,25 (OH) Vitamin D = 1,25-dihydroxyvitamin D.

Figure 2

Vitamin D signaling affects the expression of several genes, regulates the immune system, and modulates the inflammatory response. It helps maintain epithelial integrity, through the regulation of tight junctions and adherens junctions’ components, as well as the release of antimicrobial peptides like the defensins. A role in the integrity of the mucus layer, as well as the composition of the gut microbiome, has been advocated. Th = T helper cells; NKT = natural killer T cells; Tregs = regulatory T cells; sIgA = secretory immunoglobulin A; VDR = vitamin D receptor.

Figure 3

Vitamin D exerts its biological effects on the intestine in IBD maintaining mucosal barrier integrity, modulating the immune system and the composition of the gut microbiota. Emerging evidence suggests that vitamin D deficiency may unfavorably affect response to biological therapy, being associated with an increased risk of both primary non-response and secondary loss of response to the drugs. Furthermore, vitamin D deficiency may worsen corticosteroid-related osteopenia/osteoporosis and increase the risk of immunomodulator-related infections.