Involvement of the Gut Microbes Romboutsia hominis and Akkermansia muciniphila in the Pathophysiology and Development of Nonalcoholic Steatohepatitis

Background Nonalcoholic steatohepatitis (NASH) 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 NASH. We have established a NASH murine model that closely mimics NASH pathophysiology using a high-fat, marginal methionine-supplemented, choline-deficient (HMF) diet. Results Through this model, we identified Romboutsia hominis as a key contributor to NASH 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 NASH 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 NASH diagnosis. Conclusions These findings elucidate critical mechanisms within the gut–liver axis and suggest novel therapeutic and diagnostic strategies targeting gut microbiota for NASH.