Fig. 2.

Vitamin D in modulating intestinal innate immunity to determine gut microbiota. While the large intestine harbors massive number of microbes, the small intestine has a minimal level of the microbiome, indicating the existence of a gating system at the distal region of the ileum, which restrains the translocalization of gut microbes into the small intestine. The vitamin D receptor is highly expressed at the end of small intestine, and vitamin D signaling can upregulate the Paneth cell defensins that restrain bacterial growth in the small intestine. Moreover, vitamin D signaling also upregulates the tight junctions of intestinal epithelial cells and mucin expression in the Goblet cells for innate immune homeostasis. Conversely, vitamin D deficiency, which is often associated with Type 2 diabetes and nonalcoholic fatty liver disease, may lead to gut dysbiosis and endotoxemia for systemic inflammation, insulin resistance, and metabolic disorders.