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World J Hepatol. Mar 27, 2025; 17(3): 103854
Published online Mar 27, 2025. doi: 10.4254/wjh.v17.i3.103854
Gut microbiota differences, metabolite changes, and disease intervention during metabolic - dysfunction - related fatty liver progression
Jian-Zhong Shu, Yu-Han Huang, Xiao-Hong He, Feng-Ying Liu, Qian-Qian Liang, Xue-Tong Yong, Yong-Fang Xie
Jian-Zhong Shu, Department of Encephalopathy, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400015, China
Jian-Zhong Shu, Yu-Han Huang, Xiao-Hong He, Feng-Ying Liu, Qian-Qian Liang, Xue-Tong Yong, Yong-Fang Xie, School of Life Health Information Science and Engineering, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
Jian-Zhong Shu, College of Integrated Traditional Chinese and Western Medicine, Chongqing University of Traditional Chinese Medicine, Chongqing 402760, China
Yong-Fang Xie, Institute of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
Co-first authors: Jian-Zhong Shu and Yu-Han Huang.
Author contributions: Shu JZ and Huang YH contribute equally to this study as co-first authors; Shu JZ, Huang YH, He XH, Liu FY, Liang QQ, Yong XT and Xie YF designed the research study; Shu JZ, Huang YH, Liu FY, Liang QQ and Yong XT performed the literature collection and screening and drafted the original manuscript; Huang YH, He XH, Liu FY, Liang QQ and Yong XT reviewed and edited the manuscript and contributed to the visualization; He XH and Xie YF were responsible for the project administration and funding acquisition; He XH, Huang YH and Xie YF provided conceptualization.
Supported by Natural Science Foundation of Chongqing, No. cstc2021jcyj-msxmx0848; Chongqing Bishan Scientific Research Project, No. BSKJ2022006; National Natural Science Foundation of China, No. 81773954; National College Students Innovation and Entrepreneurship Program, No. 202310617015.
Conflict-of-interest statement: All the authors solemnly declare that there are no conflicts of interest in aspects such as finance, personal relationships, and intellectual property rights that might affect the fairness, objectivity, and interpretation of the research results.
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: Yong-Fang Xie, PhD, Professor, School of Life Health Information Science and Engineering, Chongqing University of Posts and Telecommunications, No. 2 Chongwen Road, Nanshan Street, Nan'an District, Chongqing 400065, China. xieyf@cqupt.edu.cn
Received: December 12, 2024
Revised: January 17, 2025
Accepted: February 12, 2025
Published online: March 27, 2025
Processing time: 113 Days and 1.6 Hours
Abstract

In the current era, metabolic dysfunction-associated steatotic liver disease (MASLD) has gradually developed into a major type of chronic liver disease that is widespread globally. Numerous studies have shown that the gut microbiota plays a crucial and indispensable role in the progression of MASLD. Currently, the gut microbiota has become one of the important entry points for the research of this disease. Therefore, the aim of this review is to elaborate on the further associations between the gut microbiota and MASLD, including the changes and differences in the microbiota between the healthy liver and the diseased liver. Meanwhile, considering that metabolic dysfunction-associated fatty liver and metabolic dysfunction-associated steatohepatitis are abnormal pathological states in the development of the disease and that the liver exhibits different degrees of fibrosis (such as mild fibrosis and severe fibrosis) during the disease progression, we also conduct a comparison of the microbiota in these states and use them as markers of disease progression. It reveals the changes in the production and action mechanisms of short-chain fatty acids and bile acids brought about by changes in the gut microbiota, and the impact of lipopolysaccharide from Gram-negative bacteria on the disease. In addition, the regulation of the gut microbiota in disease and the production and inhibition of related disease factors by the use of probiotics (including new-generation probiotics) will be explored, which will help to monitor the disease progression of patients with different gut microbiota compositions in the future and carry out personalized targeted therapies for the gut microbiota. This will achieve important progress in preventing and combating this disease.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Gut microbiota; Short-chain fatty acids; Bile acids; Lipopolysaccharides; Probiotics

Core Tip: This review elaborates in detail on the comparison of the gut microbiota between metabolic dysfunction-associated steatotic liver disease patients and healthy individuals, between metabolic dysfunction-associated fatty liver and metabolic dysfunction-associated steatohepatitis, as well as between the stages of mild fibrosis and significant fibrosis. It reveals the changes in the production and action mechanisms of short-chain fatty acids, bile acids, and lipopolysaccharides brought about by the changes in the gut microbiota. In addition, it also explores the regulation of the gut microbiota in the disease by using probiotics and the production and inhibition of related disease factors.