Gut microbial extracellular vesicles modulate the development of metabolic dysfunction-associated steatohepatitis through the gut-liver axis

Metabolic dysfunction-associated steatohepatitis (MASH) represents a growing global health challenge due to its propensity to progress to irreversible hepatic disorders, including fibrosis, cirrhosis, and carcinoma. This study aimed to investigate the role of gut microbiota in the pathogenesis of MASH. We identified Romboutsia hominis as a key contributor to MASH progression, exacerbating hepatic lipid accumulation and inflammation via the tumor necrosis factor-α (TNF-α) signaling pathway. Conversely, Akkermansia muciniphila and its extracellular vesicles (EVs) mitigated MASH by reducing hepatic lipid deposition through lipid biosynthesis-related genes downregulation. Furthermore, by integrating gut microbiota profiles and serum biomarkers using a machine learning approach, we achieved over 90% accuracy in noninvasive MASH diagnosis. These findings elucidate critical mechanisms within the gut-liver axis and suggest novel therapeutic and diagnostic strategies targeting gut microbiota and their functional EVs for MASH.