Figure 1: VDR regulates the liver-gut axis: In the liver, after VDR is activated by 1,25(OH)2D or LCA, it then heterodimerizes with FXR/RXR and binds to VDR responsive element (VDRE) region of DNA. Active VDR directly increases CYP3A4 transcription, which in turn degrades LCA. VDR activation also induces negative regulation of CYP7A1, which decreases bile acid synthesis. Thus, VDR acts as a bile acid sensor. In the intestine, VDR regulates the intestinal barrier functions by regulating epithelial tight junction proteins and blocking inflammation and bacterial infection. Thus, VDR plays a major role in linking the signaling pathways that moderate the liver-gut axis. Dysregulation of this axis might lead to increased gut permeability, bacterial translocation, and obesity.