Vitamin A and vitamin D regulate the microbial complexity, barrier function, and the mucosal immune responses to ensure intestinal homeostasis

Abstract

Diet is an important regulator of the gastrointestinal microbiota. Vitamin A and vitamin D deficiencies result in less diverse, dysbiotic microbial communities and increased susceptibility to infection or injury of the gastrointestinal tract. The vitamin A and vitamin D receptors are nuclear receptors expressed by the host, but not the microbiota. Vitamin A- and vitamin D-mediated regulation of the intestinal epithelium and mucosal immune cells underlies the effects of these nutrients on the microbiota. Vitamin A and vitamin D regulate the expression of tight junction proteins on intestinal epithelial cells that are critical for barrier function in the gut. Other shared functions of vitamin A and vitamin D include the support of innate lymphoid cells that produce IL-22, suppression of IFN-γ and IL-17 by T cells, and induction of regulatory T cells in the mucosal tissues. There are some unique functions of vitamin A and D; for example, vitamin A induces gut homing receptors on T cells, while vitamin D suppresses gut homing receptors on T cells. Together, vitamin A- and vitamin D-mediated regulation of the intestinal epithelium and mucosal immune system shape the microbial communities in the gut to maintain homeostasis.

Keywords: Vitamin A; gastrointestinal tract; microbiota; mucosal immune system; nutrition; vitamin D.

Figure 1.. The mechanisms underlying the role of vitamin A and vitamin D in the regulation of GI homeostasis and the microbiota.

Deficiency in either vitamin A or vitamin D results in dysbiosis of the microbiota and increased susceptibility to injury in the GI tract. The effects of vitamin A and vitamin D on the microbiota are as a result of the regulation of gut epithelial and immune cells. Vitamin A or D deficient animals have less diverse microbial communities and increased presence of potentially pathogenic Proteobacteria phylum members. Both vitamin A and vitamin D are important to induce ZO-1, Occludin and Claudin tight junction proteins important for the integrity of the barrier. Deficiency in either vitamin A or vitamin D results in leaky guts. In addition to gut epithelial cells, the mucosal immune system is a target of vitamin A and vitamin D. The development of ILC3 cells that produce IL-22, CD8αα and T reg cells that produce IL-10 also requires vitamin A and vitamin D. Furthermore, vitamin A and vitamin D inhibit the functions of Th1 and Th17 cells in the gut. T cell homing is regulated by vitamin A but not vitamin D. Deficiency in either vitamin A or vitamin D results in impaired barrier function, increased IL-17 and IFN-γ, reduced Treg, ILC3, IL-10 and IL-22 and dysbiosis of the microbiota. The shared effects of vitamin A and vitamin D on the host epithelial and immune cells indirectly affects the community of microbes found in the gut.