Vitamin D and intestinal homeostasis: Barrier, microbiota, and immune modulation
Hana. M.A.Fakhoury The Journal of Steroid Biochemistry and Molecular Biology Volume 200, June 2020, 105663
Highlights
• Vitamin D plays a pivotal role in maintaining intestinal homeostasis.
• Vitamin D limits microbiota entrance into the interstitium.
• Should bacteria invade the lamina propria, immune cells clear the affected site.
• Vitamin D subdues the immune response, thereby restoring homeostasis.
• Significant limitations preclude universal acceptance of vitamin D for IBD therapy.
Vitamin D plays a pivotal role in intestinal homeostasis. Vitamin D can impact the function of virtually every cell in the gut by binding to its intracellular receptor (VDR) and subsequently transcribing relevant genes. In the lumen, the mucus layer and the underlying epithelium serve to keep resident microbiota at bay. Vitamin D ensures an appropriate level of antimicrobial peptides in the mucus and maintains epithelial integrity by reinforcing intercellular junctions. Should bacteria penetrate the epithelial layer and enter the interstitium, immune sentinel cells (e.g. macrophages, dendritic cells, and innate lymphoid cells) elicit inflammation and trigger the adaptive immune response by activating Th1/Th17 cells. Vitamin D/VDR signaling in these cells ensures clearance of the bacteria.
Subsequently, vitamin D also quiets the adaptive immune system by suppressing the Th1/Th17 cells and favoring Treg cells. The importance of vitamin D/VDR signaling in intestinal homeostasis is evidenced by the development of a chronic inflammatory state (e.g. IBD) when this signaling system is disrupted.