Gut microbiota and the gut–liver axis in MASLD: mechanisms, immune regulation and therapeutic opportunities

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common chronic liver diseases worldwide, affecting more than one-third of adults and imposing a substantial hepatic and systemic metabolic burden. With the continuing rise in obesity, type 2 diabetes mellitus, and related metabolic abnormalities, the prevalence of MASLD is expected to keep increasing. This review summarizes MASLD from the overarching perspective of gut-liver axis dysregulation, focusing on alterations in gut microbial composition and function, intestinal barrier injury, disturbances in microbiota-derived metabolites, and gut microbiota-associated epigenetic and immune dysregulation during disease initiation and progression. It further integrates the overall significance of these changes in the evolution of MASLD. Finally, potential therapeutic strategies represented by fecal microbiota transplantation and natural products are briefly discussed, suggesting that targeting the gut microbiota and its related networks may provide new opportunities for MASLD prevention and treatment.