The impact of sleeve gastrectomy on MASH development by regulating the composition of gut microbiota and metabolic homeostasis

The prevalence of metabolic dysfunction-associated steatohepatitis (MASH) is increasing annually, which is a global public health issue. Although clinical trials are lacking, observational studies indicate that bariatric surgery can alleviate the progression of MASH. Here, we performed sleeve gastrectomy (SG) and Sham surgery on 8week-old mice, and then fed a AMLN diet for 24 weeks to construct a diet-inducted MASH mice model after 4week post-surgery recovery. Applying a multi-omics approach combining metagenomics, metabolomics, and transcriptomics, we found that SG prevents the development of hepatic steatosis, inflammation, and fibrosis in MASH mice not only by significantly altering the structure of gut microbiota including s_Akkermansia muciniphila, s_Alistiples dispar, g_Helicobacter and s_uc_Oscillospiraceae, but also by modulating the levels of serum metabolites including L-arginine and taurocholic acid (TCA). These results suggest that SG and the alteration of gut micro- biota and its related serum metabolites can be served as the effective therapeutic strategies for MASH.