Deciphering the gut-liver axis in MASLD: from dysbiosis-driven pathogenesis to precision microbiome therapeutics

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver disorder worldwide, characterized by a multifactorial pathogenesis involving genetic predisposition, metabolic disturbances, environmental influences, and gut microbiota interactions. In recent years, the gut microbiota has garnered significant attention for its pivotal role in MASLD development and progression through the gut-liver axis. This review comprehensively summarizes current understanding of the molecular mechanisms by which gut microbiota and their metabolites contribute to MASLD pathogenesis, including intestinal barrier dysfunction, bile acid metabolism dysregulation, abnormalities in short-chain fatty acid and tryptophan metabolism, oxidative stress, and mitochondrial impairment. Furthermore, we comprehensively discuss advances in therapeutic strategies targeting gut microbiota modulation, such as probiotics/prebiotics, fecal microbiota transplantation, dietary interventions, bioactive compounds from traditional Chinese medicine, and surgical approaches. By integrating these insights, this review aims to provide novel perspectives for precise prevention and treatment of MASLD, highlighting the gut microbiota as a promising target for future clinical management.