Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Nov 15, 2015; 6(4): 99-109
Published online Nov 15, 2015. doi: 10.4291/wjgp.v6.i4.99
Starring role of toll-like receptor-4 activation in the gut-liver axis
Simone Carotti, Michele Pier Luca Guarino, Umberto Vespasiani-Gentilucci, Sergio Morini
Simone Carotti, Sergio Morini, Laboratory of Microscopic and Ultrastructural Anatomy, School of Medicine, University Campus Bio-Medico of Rome, 00128 Rome, Italy
Michele Pier Luca Guarino, Gastroenterology Unit, School of Medicine, University Campus Bio-Medico of Rome, 00128 Rome, Italy
Umberto Vespasiani-Gentilucci, Clinical Medicine and Hepatology Unit, School of Medicine, University Campus Bio-Medico of Rome, 00128 Rome, Italy
Author contributions: Carotti S, Guarino MPL and Vespasiani-Gentilucci U contributed to the literature review and wrote the paper; Morini S contributed to the study conception, made revisions and helped with writing.
Conflict-of-interest statement: The author has no conflict of interests.
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: Sergio Morini, MD, Laboratory of Microscopic and Ultrastructural Anatomy, School of Medicine, University Campus Bio-Medico of Rome, Via Alvaro Del Portillo, 21, 00128 Rome, Italy. s.morini@unicampus.it
Telephone: +39-06-225419170 Fax: +39-06-22541456
Received: May 28, 2015
Peer-review started: May 28, 2015
First decision: July 10, 2015
Revised: July 21, 2015
Accepted: October 16, 2015
Article in press: October 19, 2015
Published online: November 15, 2015
Abstract

Since the introduction of the term “gut-liver axis”, many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extra-intestinal diseases alter microbiota composition and lead to dysbiosis, which aggravates impaired intestinal barrier function via increased lipopolysaccharide translocation. The subsequent increased passage of gut-derived product from the intestinal lumen to the organ wall and bloodstream affects gut motility and liver biology. The activation of the toll-like receptor 4 (TLR-4) likely plays a key role in both cases. This review analyzed the most recent literature on the gut-liver axis, with a particular focus on the role of TLR-4 activation. Findings that linked liver disease with dysbiosis are evaluated, and links between dysbiosis and alterations of intestinal permeability and motility are discussed. We also examine the mechanisms of translocated gut bacteria and/or the bacterial product activation of liver inflammation and fibrogenesis via activity on different hepatic cell types.

Keywords: Gut microbiota, Dysbiosis, Toll-like receptor 4, Gut motility, Lipopolysaccharide tolerance, Non-alcoholic fatty liver disease, Chronic hepatitis, Intestinal barrier function, Liver fibrosis

Core tip: Liver disease is associated with significant changes in intestinal microbiota, but whether liver disease modifies the complement of gut bacteria or dysbiosis causes liver disease is not clearly understood. This review outlines current knowledge on the gut-liver axis, with a particular focus on the role of toll-like receptor 4 activation in functional gastrointestinal disorders, liver inflammation and fibrosis.