Vitamin D necessary for mucosal barrier function

Vitamin D is necessary for far more than calcium homeostasis. It has long been known to be essential for immune system balance through its crucial role in the production of regulatory T cells (Treg) and the anti-inflammatory cytokine IL-10 (interleukin-10) that prevent an overzealous immune system from unleashing autoimmune inflammation. There is evidence that vitamin D is required to sustain barrier system (gastrointestinal, respiratory, blood-brain) integrity, degradation of which is a prime contributor to loss of immune tolerance. A review published in Current Opinion in Gastroenterology discusses the role of vitamin D and the vitamin D receptor in mucosal immune function.

"There is now an increasing amount of evidence to show that 1,25(OH)₂D₃, the most active metabolite of Vitamin D, regulates the immune response and possesses anti-inflammatory activity...Vitamin D deficiency is a critical factor in the pathology of at least 17 varieties of cancer as well as autoimmune diseases, diabetes, osteoarthritis, periodontal disease, and more. These data suggest that Vitamin D functions in a wide variety of diseases."

The vitamin D receptor (VDR) stabilizes the barrier epithelium

The VDR is active in many functions throughout the body including immune system balance and regulation of inflammation.

"VDR is a nuclear receptor that mediates most known functions of 1,25(OH)₂D₃. Active VDR affects transcription of at least 913 genes and impacts processes ranging from calcium metabolism to the expression of key antimicrobial peptides...It has also been shown that VDR stabilizes cell tight junction structures in the intestinal epithelial cells; hence, proper functioning of VDR is needed to control intestinal homeostasis."

This function is fundamental to a wide range of disorders...

"In summary, the regulation of T cells, B cells, macrophages, dendritic cells, and epithelial cells by 1,25(OH)₂D₃ and VDR provides a link between Vitamin D and many autoimmune diseases, including IBD, juvenile diabetes mellitus, multiple sclerosis, asthma, and rheumatoid arthritis...Manipulating the level of 1,25(OH)₂D₃ in the body and restoring the function of VDR may represent a new approach to treating autoimmune diseases. 1,25(OH)₂D₃ has potent immunomodulatory properties that have promoted its potential use in the prevention and treatment of infectious disease and autoimmune conditions."

Vitamin D deficiency promotes barrier dysfunction and intestinal inflammation

The authors of a study published in The Journal of Infectious Diseases illuminate the role of vitamin D in protection of the intestinal barrier in the presence of infection. The authors state:

"Vitamin D, an important modulator of the immune system, has been shown to protect mucosal barrier homeostasis. This study investigates the effects of vitamin D deficiency on infection-induced changes in intestinal epithelial barrier function in vitro and on Citrobacter rodentium–induced colitis in mice. "

Their metrics for intestinal barrier integrity included histological analysis, intestinal permeability assay, measurement of inflammatory cytokine levels, and microbiome analysis. The importance of vitamin D is clearly apparent:

"1,25(OH)₂D₃ altered E. coli O157:H7–induced reductions in transepithelial electrical resistance, decreased permeability, and preserved barrier integrity. Vitamin D–deficient mice challenged with C. rodentium demonstrated increased colonic hyperplasia and epithelial barrier dysfunction. Vitamin D deficiency resulted in an altered composition of the fecal microbiome both in the absence and presence of C. rodentium infection."

It's known that even a bout with food-borne illness can cause loss of immune tolerance for the normal commensal gut microbiota (see Acute gastrointestinal infection can turn on autoimmune disorders). The authors' conclusion suggests how suboptimal vitamin D could contribute to this complication:

"This study demonstrates that vitamin D is an important mediator of intestinal epithelial defenses against infectious agents. Vitamin D deficiency predisposes to more-severe intestinal injury in an infectious model of colitis."

Clinical Note

Considering the fundamental importance of barrier system integrity in autoimmune disorders, optimizing vitamin D and VDR function should always be included in case management.