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REVIEW article

Front. Immunol.

Sec. Nutritional Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1682755

This article is part of the Research TopicThe Role of Bioactive Compounds and Nutrients in Intestinal Mucosal Immunity, Liver and Vascular InflammationView all 4 articles

Molecular Mechanisms and Clinical Applications of Gut Microbiota-Derived Bioactive Compounds in Metabolic Dysfunction-Associated Fatty Liver Disease

Provisionally accepted
Chengyun  MaChengyun Ma1Jing  WangJing Wang1Xuanli  SongXuanli Song2Xue  WangXue Wang3Shuai  ZongShuai Zong1*
  • 1Shandong Provincial Hospital, Jinan, China
  • 2Jinan Municipal Center for Disease Control and Prevention, Jinan, China
  • 3Qilu Hospital of Shandong University, Jinan, China

The final, formatted version of the article will be published soon.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) has emerged as a leading cause of chronic liver disease worldwide. Its pathogenesis is closely associated with gut microbiota dysbiosis and metabolic disturbances. In recent years, numerous studies have demonstrated that bioactive compounds produced by gut microbial metabolism—such as short-chain fatty acids, secondary bile acids, tryptophan derivatives, and bacterial extracellular vesicles—play critical roles in the development and progression of MAFLD by modulating hepatic lipid metabolism, inflammatory responses, and epigenetic regulation. The characteristic expression patterns of these gut microbiota-derived bioactive compounds provide novel options for differential diagnosis of the disease. Moreover, elucidation of the underlying pathological mechanisms has paved novel avenues for MAFLD treatment. Strategies including dietary interventions, prebiotics, probiotics, and other microbiota-targeted therapies are considered potential approaches to modulate MAFLD progression. This review systematically summarizes the molecular mechanisms underlying the development of MAFLD influenced by gut microbiota-derived bioactive compounds. It also explores the feasibility of utilizing specific gut microbial metabolite profiles for MAFLD diagnosis and highlights potential therapeutic strategies targeting microbiota-host metabolic interactions, including the use of engineered bacteria to produce specific metabolites, probiotic/prebiotic interventions, and the clinical prospects of fecal microbiota transplantation.

Keywords: Metabolic dysfunction-associated fatty liver disease, Gut Microbiota-Derived Bioactive Compound, microbiota-host crosstalk, Pathogenesis, clinical application

Received: 09 Aug 2025; Accepted: 29 Sep 2025.

Copyright: © 2025 Ma, Wang, Song, Wang and Zong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Shuai Zong, zongzong_1115@163.com

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