Zhang CY, Liu S, Sui YX, Yang M. Roles of short-chain fatty acids in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis. World J Hepatol 2025; 17(11): 113756 [DOI: 10.4254/wjh.v17.i11.113756]
Corresponding Author of This Article
Ming Yang, PhD, Assistant Professor, Department of Surgery, University of Connecticut, School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, United States. minyang@uchc.edu
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Gastroenterology & Hepatology
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Review
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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/
Nov 27, 2025 (publication date) through Dec 4, 2025
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World Journal of Hepatology
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1948-5182
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Zhang CY, Liu S, Sui YX, Yang M. Roles of short-chain fatty acids in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis. World J Hepatol 2025; 17(11): 113756 [DOI: 10.4254/wjh.v17.i11.113756]
World J Hepatol. Nov 27, 2025; 17(11): 113756 Published online Nov 27, 2025. doi: 10.4254/wjh.v17.i11.113756
Roles of short-chain fatty acids in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis
Chun-Ye Zhang, Shuai Liu, Yu-Xiang Sui, Ming Yang
Chun-Ye Zhang, Bond Life Sciences Center, University of Missouri, Columbia, MO 65212, United States
Shuai Liu, The First Affiliated Hospital, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
Yu-Xiang Sui, School of Life Science, Shanxi Normal University, Linfen 041004, Shanxi Province, China
Ming Yang, Department of Surgery, University of Connecticut, School of Medicine, Farmington, CT 06030, United States
Author contributions: Zhang CY, Liu S, Sui Y, and Yang M designed, wrote, revised, and finalized the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for 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: Ming Yang, PhD, Assistant Professor, Department of Surgery, University of Connecticut, School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, United States. minyang@uchc.edu
Received: September 2, 2025 Revised: October 25, 2025 Accepted: October 30, 2025 Published online: November 27, 2025 Processing time: 86 Days and 5.8 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, affecting more than 30% of adults and 7%-14% of youths globally. MASLD and its advanced form of metabolic dysfunction-associated steatohepatitis (MASH) can progress to liver cirrhosis and hepatocellular carcinoma. Despite its growing burden, effective therapies for MASLD and MASH remain limited. Accumulating evidence indicates that short-chain fatty acids (SCFAs) modulate the activation of hepatic innate and adaptive immune cells, influencing liver inflammation and fibrosis. Moreover, SCFAs modulate liver lipid and glucose metabolism and insulin sensitivity, affecting MASLD progression. This review summarizes the cellular and molecular mechanisms through which SCFAs impact liver inflammation, fibrosis, and energy metabolism. Several key molecular signaling pathways are discussed. Clinical trials aiming to modulate SCFA production through different treatments are reviewed. Collectively, emerging evidence supports that targeting SCFA-mediated function represents a promising therapeutic strategy for MASLD and MASH.
Core Tip: Short-chain fatty acids (SCFAs) produced by gut microbial fermentation of indigestible fiber play important roles in regulating liver inflammation, fibrosis, and energy metabolism. The common SCFAs in the gut and liver are acetate, butyrate, and propionate. Strategies that enhance SCFA production, such as probiotic or dietary fiber supplementation, bariatric surgery, ketohexokinase inhibition, or fecal microbiota transplantation, offer promising methods for preventing metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis.
