Role of pregnane X-receptor in regulating bacterial translocation in chronic liver diseases

Abstract

Bacterial translocation (BT) has been impeccably implicated as a driving factor in the pathogenesis of a spectrum of chronic liver diseases (CLD). Scientific evidence accumulated over the last four decades has implied that the disease pathologies in CLD and BT are connected as a loop in the gut-liver axis and exacerbate each other. Pregnane X receptor (PXR) is a ligand-activated transcription factor and nuclear receptor that is expressed ubiquitously along the gut-liver-axis. PXR has been intricately associated with the regulation of various mechanisms attributed in causing BT. The importance of PXR as the mechanistic linker molecule in the gut-liver axis and its role in regulating bacterial interactions with the host in CLD has not been explored. PubMed was used to perform an extensive literature search using the keywords PXR and bacterial translocation, PXR and chronic liver disease including cirrhosis. In an adequate expression state, PXR acts as a sensor for bile acid dysregulation and bacterial derived metabolites, and in response shapes the immune profile beneficial to the host. Activation of PXR could be therapeutic in CLD as it counter-regulates endotoxin mediated inflammation and maintains the integrity of intestinal epithelium. This review mainly focuses PXR function and its regulation in BT in the context of chronic liver diseases.

Keywords: Pregnane X receptor, Bacterial translocation, Chronic liver disease, Intestinal permeability, Inflammation, Tight junctions

Core tip: Translocation of bacteria at pathological levels is a major driving factor in the progression of chronic liver diseases (CLD). However, it remains to be known whether it is the CLD condition that triggers leaky gut, or if translocation of bacteria plays an etiological role in the pathogenesis of CLD. Dysregulation of homeostasis in the gut-liver axis is considered as a crucial element that underlies the pathogenesis of BT. The nuclear receptor, pregnane X receptor (PXR) is widely expressed in gut and liver axis and is implicated in maintenance of equilibrium in the gut-liver axis. This review will summarize the various studies that have highlighted the importance of PXR as the mechanistic linker molecule in the gut-liver axis and its role in regulating bacterial translocation in the pathogenesis of cirrhosis.