Review
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 18, 2017; 9(32): 1210-1226
Published online Nov 18, 2017. doi: 10.4254/wjh.v9.i32.1210
Role of pregnane X-receptor in regulating bacterial translocation in chronic liver diseases
Sundhar Mohandas, Balasubramaniyan Vairappan
Sundhar Mohandas, Balasubramaniyan Vairappan, Liver Diseases Research Lab, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantari Nagar, Pondicherry 605006, India
Author contributions: Both authors equally contributed to this review with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: None declared.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Balasubramaniyan Vairappan, Assistant Professor, Liver Diseases Research Lab, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Puducherry 605006, India. balamaniyan@gmail.com
Telephone: +91-960-0461977
Received: August 21, 2017
Peer-review started: August 22, 2017
First decision: September 19, 2017
Revised: September 21, 2017
Accepted: October 30, 2017
Article in press: October 30, 2017
Published online: November 18, 2017
Processing time: 86 Days and 17.1 Hours
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.