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March 15, 2026The FASEB Journal4 citations

The Gut‐Liver Axis in Metabolic Dysfunction‐Associated Steatotic Liver Disease: From Mechanistic Insights to Precision Therapeutics

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SZShaoliang ZhuMZMengjie ZouQWQijun Wu

Key Points

  • This review synthesizes recent advances in understanding and treating metabolic dysfunction-associated steatotic liver disease (MASLD).
  • Analyzed landmark clinical trials focusing on MASLD.
  • Reviewed developments in next-generation probiotics and fecal microbiota transplantation (FMT).
  • Integrated artificial intelligence with multiomics for diagnostics of MASLD.
  • Examined the interplay between host genetics and the gut microbiome in MASLD progression.
  • Established causal links between gut dysbiosis and MASLD pathology.
  • Fecal microbiota transplantation (FMT) effectively prevents hepatic encephalopathy recurrence.
  • Next-generation probiotics like Akkermansia muciniphila are under MASLD-specific trials.
  • AI-driven diagnostic tools gained regulatory qualification from the European Medicines Agency.

Abstract

ABSTRACT Metabolic dysfunction‐associated steatotic liver disease (MASLD) has become the most prevalent chronic liver condition globally, shifting the diagnostic paradigm toward an affirmative, metabolism‐focused framework. The gut‐liver axis is a central pathophysiological pathway. This review aims to synthesize revolutionary advances from 2023 to 2025 in understanding and treating MASLD by focusing on the gut microbiome's role. This comprehensive review analyzes cutting‐edge research published between 2023 and 2025. We examined evidence from landmark clinical trials, developments in next‐generation probiotics, the integration of artificial intelligence (AI) with multiomics for diagnostics, and studies clarifying the interplay between host genetics and the microbiome in MASLD pathogenesis. Causal links between gut dysbiosis and MASLD pathology are now firmly established. Fecal microbiota transplantation (FMT) effectively prevents hepatic encephalopathy recurrence, and next‐generation probiotics like Akkermansia muciniphila have entered MASLD‐specific trials. AI‐driven diagnostic tools have achieved regulatory qualification from the European Medicines Agency. Furthermore, host genetics, particularly PNPLA3 variants, are shown to not only predispose to MASLD but also shape specific microbial communities that functionally contribute to disease progression. The field is rapidly advancing from correlative observations to causal evidence, enabling the development of microbiome‐based biomarkers and personalized therapies. The future of MASLD management lies in precision strategies, such as bacteriophage therapy and functionally defined probiotics, which integrate metabolic, microbial, and genetic factors into individualized care, heralding a new therapeutic era.

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Cite This Study

Zhu et al. (2026) studied this question.

synapsesocial.com/papers/69b606d583145bc643d1d27bhttps://doi.org/10.1096/fj.202503607rr
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