Rusman RD, Akil F, Parewangi ML, Daud NA, Bachtiar R, Kusuma SH, Rifai A. Gut microbiota and metabolic-associated steatosis liver disease: Unveiling mechanisms and opportunities for therapeutic intervention. World J Exp Med 2025; 15(4): 107316 [DOI: 10.5493/wjem.v15.i4.107316]
Corresponding Author of This Article
Resha Dermawansyah Rusman, MD, Division of Gastroenterology-Hepatology, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10, Makassar 90245, Sulawesi Selatan, Indonesia. reshadermawan@unhas.ac.id
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Minireviews
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 Exp Med. Dec 20, 2025; 15(4): 107316 Published online Dec 20, 2025. doi: 10.5493/wjem.v15.i4.107316
Gut microbiota and metabolic-associated steatosis liver disease: Unveiling mechanisms and opportunities for therapeutic intervention
Resha Dermawansyah Rusman, Fardah Akil, Muhammad Luthfi Parewangi, Nu'man AS Daud, Rini Bachtiar, Susanto Hendra Kusuma, Amelia Rifai
Resha Dermawansyah Rusman, Fardah Akil, Muhammad Luthfi Parewangi, Nu'man AS Daud, Rini Bachtiar, Susanto Hendra Kusuma, Amelia Rifai, Division of Gastroenterology-Hepatology, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Makassar 90245, Sulawesi Selatan, Indonesia
Author contributions: Rusman RD conceived and designed the study, collected the data, performed the analysis, and drafted the manuscript; Akil F and Parewangi ML supervised the study and provided critical revisions and intellectual input; Daud NAS and Bachtiar R contributed to data interpretation and literature review; Kusuma SH and Rifai A assisted in manuscript editing and final approval of the version to be published; All authors read and approved the final manuscript.
Conflict-of-interest statement: All authors have no conflicts of interest to declare.
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: Resha Dermawansyah Rusman, MD, Division of Gastroenterology-Hepatology, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Jl. Perintis Kemerdekaan Km. 10, Makassar 90245, Sulawesi Selatan, Indonesia. reshadermawan@unhas.ac.id
Received: May 30, 2025 Revised: July 3, 2025 Accepted: September 18, 2025 Published online: December 20, 2025 Processing time: 204 Days and 2.8 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease, closely linked with metabolic syndrome. Recent evidence spotlights the gut–liver axis as a major player in MASLD pathogenesis. Dysbiosis of gut microbiota alters the intestinal barrier and enhances endotoxemia, hepatic inflammation, insulin resistance and fibrosis. Microbial metabolites including short-chain fatty acids, bile acids and ethanol impact host metabolism and immunity, and their dysregulation contributes to disease progression. This review summarises the mechanistic associations between dysbiosis and MASLD involving altered microbial composition, leaky gut, toll-like receptor signalling and immune dysregulation. It also reviews microbially targeted therapeutic strategies, such as probiotics, prebiotics, synbiotics, faecal microbiota transplantation, diet changes, and postbiotic metabolites. Although these interventions may have clinical potential, the heterogeneity of outcomes highlights the interindividual nature of the microbiome and warrant personalized interventions. Developments in multi-omics and precision medicine provide possibilities to discover microbial biomarkers and customize therapeutic approach. Resolving methodological heterogeneity and providing a clear definition of MASLD-related dysbiosis are key for translating microbiome science into the clinic. In conclusion, modulation of gut microbiota is an emerging strategy for the adjunctive treatment of MASLD alongside lifestyle and pharmacologic therapies.
Core Tip: Metabolic-associated steatotic liver disease (MASLD) has developed into a worldwide health dilemma closely related to metabolic diseases such as obesity and type 2 diabetes mellitus. Mounting evidence highlights the importance of the gut microbiota in the pathogenesis of MASLD, as gut dysbiosis induced by increased gut permeability, endotoxemia and the action of microbial metabolites have been demonstrated to lead to hepatic steatosis, inflammation and fibrosis. Therapeutic potential of modulating gut microbiota with probiotics, prebiotics, synbiotics and microbiota-derived interventions is an emerging approach. Herein, we cover the gut–liver axis in MASLD drawing on insights from mechanistic pathways to microbiota-based therapeutic strategies that may transform MASLD management.
