The Role of Vitamin D in Inflammatory Bowel Disease: Mechanism to Management

Abstract

Vitamin D has been linked to human health benefits that extend far beyond its established actions on calcium homeostasis and bone metabolism. One of the most well studied facets of extra-skeletal vitamin D is its activity as an immuno-modulator, in particular its potent anti-inflammatory effects. As a consequence, vitamin D deficiency has been associated with inflammatory diseases including inflammatory bowel disease (IBD). Low serum levels of the major circulating form of vitamin D, 25-hydroxyvitamin D (25-OH-D) are significantly more prevalent in patients with IBD, particularly in the winter and spring months when UV-induced synthesis of vitamin D is lower. Dietary malabsorption of vitamin D may also contribute to low serum 25(OH)D in IBD. The benefits of supplementation with vitamin D for IBD patients are still unclear, and improved vitamin D status may help to prevent the onset of IBD as well as ameliorating disease severity. Beneficial effects of vitamin D in IBD are supported by pre-clinical studies, notably with mouse models, where the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)2D) has been shown to regulate gastrointestinal microbiota function, and promote anti-inflammatory, tolerogenic immune responses. The current narrative review aims to summarise the different strands of data linking vitamin D and IBD, whilst also outlining the possible beneficial effects of vitamin D supplementation in managing IBD in humans.

Keywords: Crohn’s disease; IBD; deficiency; supplementation; ulcerative colitis; vitamin D.

Figure 1

Vitamin D and barrier function in the gastrointestinal tract. Schematic representation of the expression of the vitamin D receptor (VDR) and vitamin D-activating enzyme (CYP27B1) in human colonic epithelial cells, antigen presenting cells such as dendritic cells (DC), and T cells. Immune responses to vitamin D occur either via systemic 1,25-dihydroxyvitamin D (1,25-(OH)2D) or local conversion of 25-hydroxyvitamin D (25-OH-D) to 1,25-(OH)2D. Possible target mechanisms include: 1) interface with microbiota (induction of antibacterials such as angiogenin, cathelcidin (LL37), defensins or intracellular pathogen recognition proteins such as nucleotide-binding oligomerisation domain containing 2 (NOD2)); 2) T cell homing to sites of inflammation; 3) suppression of inflammatory Th17 and Th1 cells and induction of tolerogenic Treg and Th2 cells; 4) enhanced expression of epithelial membrane junction proteins