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  • Review Article
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Gut microbiome in metabolic dysfunction-associated steatotic liver disease and associated hepatocellular carcinoma

Nature Reviews Gastroenterology & Hepatology volume 22, pages 619–638 (2025)Cite this article

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Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting billions of the global population. It can gradually progress to more severe diseases, including steatohepatitis, cirrhosis and hepatocellular carcinoma. Studies have highlighted the importance of the gut microbiome in the pathogenesis and progression of MASLD. On the other hand, increasing evidence has revealed the clinical potential of targeting the gut microbiome to treat MASLD. In this Review, we summarize gut microbial alterations in MASLD, metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma. The mechanisms by which a dysregulated gut–liver axis contributes to disease progression are also described, including intestinal barrier dysfunction, chronic inflammation, and altered metabolic pathways (for example, bile acids) and microbial-derived metabolites (for example, short-chain fatty acids, tryptophan derivatives and endogenous ethanol). In addition, we discuss the clinical implications of utilizing the gut microbiome as a diagnostic biomarker and the therapeutic approaches to treat MASLD and related diseases such as faecal microbiota transplantation, probiotics and engineered bacteria, prebiotics and postbiotics, microbial-derived metabolites, antimicrobials and bacteriophages. Finally, we discuss current challenges in basic and translational research on the microbiome in MASLD and propose future directions to drive progress in this field.

Key points

  • Progression from metabolic dysfunction-associated steatotic liver disease (MASLD) to steatohepatitis, fibrosis, cirrhosis and, eventually, hepatocellular carcinoma is closely associated with gut microbial dysbiosis and a dysfunctional gut–liver axis.

  • As MASLD progresses, the gut microbiome exhibits enriched Proteobacteria, Clostridium and Streptococcus as well as depleted beneficial bacteria including Eubacterium and Faecalibacterium.

  • A dysregulated gut–liver axis as well as microbial dysbiosis promote MASLD progression by impairing the intestinal barrier, altering microbial-mediated metabolic pathways and metabolites, and contributing to chronic inflammation in the liver.

  • Gut microorganisms and metabolites can be utilized as diagnostic biomarkers of MASLD, which have been shown to stratify individuals predisposed to an increased risk of disease progression with high accuracy.

  • Owing to its pivotal role, emerging studies have developed various therapeutic approaches that target the gut microbiome to treat MASLD, including faecal microbiota transplantation, probiotics, prebiotics and postbiotics, antimicrobials, microbial-derived metabolites and bacteriophages.

  • Research into the microbiome in MASLD is challenged by the lack of mechanistic understanding and consistency across studies, and unclear duration, dosage and efficacy have limited the clinical application of microbiome-targeting interventions.

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Fig. 1: Gut–liver axis and gut microbiome alterations during MASLD progression.
Fig. 2: Gut microbiome-mediated mechanisms in MASLD.
Fig. 3: Clinical implications of the gut microbiome in MASLD treatment.

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Acknowledgements

The authors were supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0500200), the National Natural Science Foundation of China (82222901 and 82272619) and the Research Grants Council-General Research Fund (CUHK14117422, CUHK14119524 and CUHK14117123).

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  1. These authors contributed equally: Harry Cheuk-Hay Lau, Xiang Zhang.

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  1. Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China

    Harry Cheuk-Hay Lau, Xiang Zhang & Jun Yu

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  1. Harry Cheuk-Hay Lau
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H.C.-H.L. and X.Z. researched data for the article and wrote the manuscript. J.Y. made a substantial contribution to discussion of content and reviewed/edited the manuscript before submission.

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Correspondence to Jun Yu.

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Lau, H.CH., Zhang, X. & Yu, J. Gut microbiome in metabolic dysfunction-associated steatotic liver disease and associated hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 22, 619–638 (2025). https://doi.org/10.1038/s41575-025-01089-1

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