Vitamin D signaling maintains intestinal innate immunity and gut microbiota: potential intervention for metabolic syndrome and NAFLD

Abstract

A lack of sunlight exposure, residence in the northern latitudes, and dietary vitamin D insufficiency are coprevalent with metabolic syndrome (MetS), Type 2 diabetes (T2D), and nonalcoholic fatty liver diseases (NAFLD), implying a potential causality and underlying mechanism. Whether vitamin D supplementation or treatment can improve these disorders is controversial, in part, because of the absence of large-scale trials. Experimental investigations, on the other hand, have uncovered novel biological functions of vitamin D in development, tumor suppression, and immune regulation, far beyond its original role as a vitamin that maintained calcium homeostasis. While the large intestine harbors massive numbers of microbes, the small intestine has a minimal quantity of bacteria, indicating the existence of a gating system located in the distal region of the small intestine that may restrain bacterial translocation to the small intestine. Vitamin D receptor (VDR) was found to be highly expressed at the distal region of small intestine, where the vitamin D signaling promotes innate immunity, including the expression of α-defensins by Paneth cells, and maintains the intestinal tight junctions. Thus, a new hypothesis is emerging, indicating that vitamin D deficiency may impair the intestinal innate immunity, including downregulation of Paneth cell defensins, leading to bacterial translocation, endotoxemia, systemic inflammation, insulin resistance, and hepatic steatosis. Here, we review the studies for vitamin D for innate immunity and metabolic homeostasis, and we outline the clinical trials of vitamin D for mitigating MetS, T2D, and NAFLD.

Influences of Vitamin D Levels and Vitamin D-Binding Protein Polymorphisms on Nonalcoholic Fatty Liver Disease Risk in a Chinese Population

“…The physiological functions of VDBP are diverse. Specifically, VDBP is the primary plasma transporter for VD and its metabolites, and may promote Mets, type-2 diabetes, and NAFLD occurrence by affecting plasma levels of VD [46]; VDBP is a transport of fatty acids and may be related with lipid metabolism [47]; VDBP plays a role in inflammatory process by activating macrophage and C5a-mediated chemotaxis [48]. All the functions suggested that VDBP may have the potential effects on the pathogenesis of NAFLD.…”

Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity

“…One area of intense interest in the field is the association between altered gut microbiota and their metabolites and NAFLD [47]. Indeed, vitamin D status may influence the severity of NAFLD through its effects on intestinal innate immunity and gut microbial composition [48]. There is also some indirect support for a potential role of vitamin D-regulated AMPs in attenuating NAFLD.…”

The role of vitamin A and vitamin D in the modulation of the immune response with focus on innate lymphoid cells

“…Such processes are important for intracellular bacteria killing [ 43 ]. Evidence from animal studies demonstrates that lacking vitamin D impairs gut innate immunity, leading to gut dysbiosis and systemic inflammation [ 44 ]. In addition, vitamin D 3 improves protective effects of other cells participating in the innate immune system as first-barrier defenses, such as keratinocytes, epithelial, intestinal, lung and corneal cells, and placenta trophoblasts [ 45 ].…”