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

Yilan Zeng, Mei Luo, Liwei Pan, Yuan Chen, Siqi Guo, Dongxia Luo, Li Zhu, Yong Liu, Lisha Pan, Siya Xu, Ruofei Zhang, Chunyan Zhang, Pengfei Wu, Liangpeng Ge, Mazen Noureddin, Stephen J. Pandol, Yuan Ping Han

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)G542-G553
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number3
StatePublished - 2020


  • Metabolic syndrome
  • Microbiota
  • Non-alcoholic fatty liver diseases
  • Small intestine
  • Vitamin D

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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