Gastrointestinal Health, Vitamin D, and VDR - May 2026

Immunomodulation by Vitamins: Mechanistic insights and clinical translation

Front. Nutr., 17 May 2026. Sec. Nutritional Immunology https://doi.org/10.3389/fnut.2026.1807154

Samuel G. Sonsalla 1, Jennifer Armbruster-Lee 2,3,4, Amali E. Samarasinghe 1,4*

Since its discovery as an antirachitic agent, vitamin D has been recognized for its importance to health, most namely bone health, prompting food fortification practices that are still in place today. The two forms of vitamin D, ergocalciferol (D2) and cholecalciferol (D3), are obtained through the diet or synthesized in the skin via ultraviolet-B radiation. Vitamin D is activated by enzymes mainly found in hepatic and renal tissues, to exert downstream effects via the nuclear vitamin D receptor (VDR). VDR is expressed nearly in all tissues, allowing activated vitamin D to have pleiotropic functions. This review focuses on the gastrointestinal tract, with high VDR content and known associations between vitamin D deficiency and disease states. For example, VDR expression within esophageal submucosal glands may influence fibrosis in eosinophilic esophagitis, while in the stomach VDR is associated with malignancy and Heliocobacter pylori infection. Intestinal diseases like inflammatory bowel disease, intestinal failure, and irritable bowel syndrome have also been linked to vitamin D deficiency and VDR expression. Although there are studies focused on the impact of genetic polymorphisms in VDR and vitamin D supplementation on intestinal diseases, they remain largely inconclusive at this time. Interest in the gut-lung axis has further prompted the investigation of vitamin D in respiratory conditions like chronic pulmonary obstructive disease, asthma, and Mycobacterium tuberculosis infection. While it is clear that vitamin D is important to both the gut and the lungs, there is still a need for further research on the overall role of this important vitamin.

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