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Vitamin D Receptor, Dysbiosis and Intestinal Microbiome Function

nurseThe microbiome modulates numerous aspects of human physiology and is a crucial factor in the development of various human diseases. Vitamin D deficiency and downregulation of the vitamin D receptor (VDR) are also associated with the pathogenesis of diseases such as inflammatory bowel disease, cancers, obesity, diabetes and asthma(1). VDR is a nuclear receptor that regulates the expression of antimicrobial peptides and autophagy regulator ATG16L1. The Paneth cell is a unique intestinal epithelial cell that can sense the gut microbiome and secrete anti-microbial peptides, thereby playing critical roles in the maintenance of homeostasis at the intestinal microbial interface(2). These roles in regulating innate immunity and intestinal microbial ecology are dependent on a functional autophagy pathway through ATG16L1, a regulator for autophagy and a risk gene for inflammatory bowel disease (IBD)(1,2). Researchers demonstrated that a low VDR level in the intestine is associated with abnormal Paneth cells, impaired autophagy function, and imbalance bacterial profile (dysbiosis), accompanied by a reduction of ATG16L1. They determined that VDR transcriptionally regulates ATG16L1 as a VDR target gene. Interestingly, administration of butyrate increases intestinal VDR expression and suppresses inflammation in a colitis model(2). Research indicates that VDR may be a determinant of IBD risk through its actions on ATG16L1, and these findings and insights can be leveraged to define therapeutic targets for restoring Paneth cells and autophagy through VDR in chronic inflammation, and may have applicability for infectious disease and autoimmune diseases where the host is in contact with bacteria.

1. Jin D, et al. Lack of Vitamin D Receptor Causes Dysbiosis and Changes the Functions of the Murine Intestinal Microbiome. Clin Ther. 2015 May 1;37(5):996-1009.e7. doi: 10.1016/j.clinthera.2015.04.004
2. Sun J. VDR/vitamin D receptor regulates autophagic activity trough ATG16L1. Autophagy. 2015 July 28: 1057-1058

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