Rochoń J, Kalinowski P, Szymanek-Majchrzak K, Grąt M. Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease. World J Gastroenterol 2024; 30(23): 2964-2980 [DOI: 10.3748/wjg.v30.i23.2964]
Corresponding Author of This Article
Piotr Kalinowski, MD, PhD, Associate Professor, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha 1a st., Warsaw 02-097, Poland. piotr.kalinowski@wum.edu.pl
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
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/
World J Gastroenterol. Jun 21, 2024; 30(23): 2964-2980 Published online Jun 21, 2024. doi: 10.3748/wjg.v30.i23.2964
Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease
Jakub Rochoń, Piotr Kalinowski, Ksenia Szymanek-Majchrzak, Michał Grąt
Jakub Rochoń, Piotr Kalinowski, Michał Grąt, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw 02-097, Poland
Ksenia Szymanek-Majchrzak, Department of Medical Microbiology, Medical University of Warsaw, Warsaw 02-004, Poland
Author contributions: Rochoń J and Kalinowski P reviewed the literature and drafted the original manuscript; Rochoń J and Szymanek-Majchrzak K designed the figures; Rochoń J, Kalinowski P, Szymanek-Majchrzak K and Grąt M critically revised the manuscript for important intellectual content. All of the authors contributed to the study conception and design. All authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest related to this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Piotr Kalinowski, MD, PhD, Associate Professor, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha 1a st., Warsaw 02-097, Poland. piotr.kalinowski@wum.edu.pl
Received: February 29, 2024 Revised: May 8, 2024 Accepted: May 24, 2024 Published online: June 21, 2024 Processing time: 112 Days and 8 Hours
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a hepatic manifestation of the metabolic syndrome. It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries. MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma. Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis. The mechanisms involved in maintaining gut-liver axis homeostasis are complex. One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gut-liver axis functionality. An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis. Moreover, alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of drugs developed for the treatment of type 2 diabetes mellitus. They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis. The mechanisms reported to be involved in this effect include an improved regulation of glycemia, reduced lipid synthesis, β-oxidation of free fatty acids, and induction of autophagy in hepatic cells. Recently, multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment. A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD. This review presents the current understanding of the role of the gut-liver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.
Core Tip: Dysbiosis of gut microbiota leading to gut-liver axis disruption is a significant contributor to the development of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the precise role of enteric bacteria in the pathogenesis of MAFLD remains unclear. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may modulate MAFLD progression mechanisms to alleviate dysfunction, partly by modifying gut microbiota. The association between MAFLD pathogenesis and gut microbiota dysbiosis needs to be understood, as well as how GLP-1 RAs can regulate these impaired mechanisms and improve patient outcomes.
