Role of Gut Microbiota-derived Metabolites in the Pathogenesis and Progression of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD): A Systematic Review

Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked with significant comorbidities and mortality. Evidence suggests that gut microbiota-derived metabolites play a vital role in the initiation and progression of MASLD. This systematic review aimed to evaluate the role of these metabolites in the pathogenesis and progression of MASLD, including steatosis, steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC).

Methods

This systematic review followed the Preferred Reporting of Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A systematic literature search was conducted across PubMed/Medline, Embase, Web of Science, and Scopus from inception to December 2025. Eligible studies included observational, interventional, animal, and in vitro mechanistic studies. Human observational studies were evaluated using the Newcastle-Ottawa scale, randomized controlled trials using the Cochrane risk of bias-2 (ROB-2) tool, and in vitro studies using a qualitative mechanistic approach. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool for animal studies. Results were synthesized narratively due to heterogeneity in the data. This study was registered in PROSPERO (CRD420261293786).