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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2019; 25(33): 4814-4834
Published online Sep 7, 2019. doi: 10.3748/wjg.v25.i33.4814
Intestinal permeability in the pathogenesis of liver damage: From non-alcoholic fatty liver disease to liver transplantation
Alberto Nicoletti, Francesca Romana Ponziani, Marco Biolato, Venanzio Valenza, Giuseppe Marrone, Gabriele Sganga, Antonio Gasbarrini, Luca Miele, Antonio Grieco
Alberto Nicoletti, Francesca Romana Ponziani, Marco Biolato, Venanzio Valenza, Giuseppe Marrone, Gabriele Sganga, Antonio Gasbarrini, Luca Miele, Antonio Grieco, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
Alberto Nicoletti, Francesca Romana Ponziani, Marco Biolato, Venanzio Valenza, Giuseppe Marrone, Gabriele Sganga, Antonio Gasbarrini, Luca Miele, Antonio Grieco, Università Cattolica del Sacro Cuore, Rome 00168, Italy
Author contributions: Grieco A was the guarantor and designed the review. Nicoletti A, Ponziani FR, Biolato M and Marrone G revised literature and wrote the initial manuscript. Nicoletti A conceived and draw the figures. Valenza V, Gasbarrini A, Sganga G and Miele L critically revised the article for important intellectual content.
Conflict-of-interest statement: Nothing to declare.
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/
Corresponding author: Antonio Grieco, MD, Associate Professor, Director of Liver Transplant Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Institute of Internal Medicine, Largo Agostino Gemelli No. 8, Rome 00168, Italy. antonio.grieco@unicatt.it
Telephone: +39-6-30155451 Fax: +39-6-35502775
Received: May 21, 2019
Peer-review started: May 21, 2019
First decision: June 9, 2019
Revised: July 4, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: September 7, 2019
Processing time: 109 Days and 13.8 Hours
Abstract

The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis. The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis. In this mutual relationship, the liver acts as a second firewall towards potentially harmful substances translocated from the gut, and is, in turn, is implicated in the regulation of the barrier. Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage. In particular, in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment, diet and gut dysbiosis as the primary pathogenic trigger. In advanced liver disease, intestinal permeability is enhanced by portal hypertension. The clinical consequence is an increased bacterial translocation that further worsens liver damage. Furthermore, this pathogenic mechanism is implicated in most of liver cirrhosis complications, such as spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis, hepatic encephalopathy, and hepatocellular carcinoma. After liver transplantation, the decrease in portal pressure should determine beneficial effects on the gut-liver axis, although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking. How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area, which deserves further attention.

Keywords: Bacterial translocation; Gut microbiota; Gut-liver axis; Liver disease; Cirrhosis; Mediterranean diet; Personalized medicine

Core tip: The integrity of the gut-liver axis is crucial for the maintenance of the homestasis of the organism. The disruption of the intestinal barrier and consequent increased intestinal permeability has been recently associated with the development of liver damage. This review summarizes present evidence on the relevance of the derangement of the gut-liver axis in the pathogenesis of liver damage and non-alcoholic fatty liver disease, the development of the complications of liver cirrhosis and its modifications after liver transplantation.