Soyasaponin A2 Alleviates Steatohepatitis Possibly through Regulating Bile Acids and Gut Microbiota in the Methionine and Choline‐Deficient (MCD) Diet‐induced Nonalcoholic Steatohepatitis (NASH) Mice

Scope Nonalcoholic steatohepatitis (NASH) is a chronic progressive disease with complex pathogenesis of which the bile acids (BAs) and gut microbiota are involved. Soyasaponins (SS) exhibits many health‐promoting effects including hepatoprotection, but its prevention against NASH is unclear. This study aims to investigate the preventive bioactivities of SS monomer (SS‐A 2 ) against NASH and further clarify its mechanism by targeting the BAs and gut microbiota. Methods and Results The methionine and choline deficient (MCD) diet‐fed male C57BL/6 mice were intervened with obeticholic acid or SS‐A 2 for 16 weeks. Hepatic pathology is assessed by hematoxylin‐eosin and Masson's trichrome staining. BAs in serum, liver, and colon are measured by ultra‐performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC‐TQMS). Gut microbiota in caecum are determined by 16S rDNA amplicon sequencing. In the MCD diet‐induced NASH mice, SS‐A 2 significantly reduces hepatic steatosis, lobular inflammation, ballooning, nonalcoholic fatty liver disease activity score (NAS) scores, and fibrosis, decreases Erysipelotrichaceae (Faecalibaculum) and Lactobacillaceae (Lactobacillus) and increases Desulfovibrionaceae (Desulfovibrio) . Moreover, SS‐A 2 reduces serum BAs accumulation and promotes fecal BAs excretion. SS‐A 2 changes the BAs profiles in both liver and serum and specifically increases the taurohyodeoxycholic acid (THDCA) level. Faecalibaculum is negatively correlated with serum THDCA. Conclusion SS‐A 2 alleviates steatohepatitis possibly through regulating BAs and gut microbiota in the MCD diet‐induced NASH mice.