Targeting the intestinal barrier with traditional Chinese medicine for non-alcoholic fatty liver disease: mechanistic insights and therapeutic perspectives

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease closely associated with metabolic dysregulation, exhibiting a complex and multifactorial pathogenesis. Recent studies demonstrate that impaired intestinal barrier function, intestinal immune barrier dysfunction, gut microbiota dysbiosis, and their associated metabolites collectively promote energy metabolism dysregulation and systemic inflammatory responses via the gut-liver axis. These interconnected processes represent key drivers in the pathogenesis and progression of NAFLD. Notably, Traditional Chinese Medicine (TCM) offers a promising therapeutic approach for NAFLD by holistically modulating intestinal barrier function, immune responses, and gut microbiota composition via multiple targets and pathways, thereby ameliorating gut dysbiosis and its downstream metabolic and inflammatory sequelae. This review systematically synthesizes the established relationship between NAFLD and intestinal barrier dysfunction. It critically evaluates current research progress on TCM interventions-including single herbs, bioactive constituents, and compound formulas-that target the intestinal barrier for NAFLD management. Key mechanistic insights into TCM efficacy are summarized, focusing on the repair of the intestinal mucosal barrier, modulation of bile acid metabolism and gut microbiota composition, and enhancement of intestinal immune barrier function. Future research should prioritize elucidating the specific molecular mechanisms underpinning TCM-mediated intestinal barrier regulation and strengthening clinical validation, ultimately advancing the scientific foundation for TCM-based NAFLD therapeutics.