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Soyasaponins (SS) exhibits many health\u2010promoting effects including hepatoprotection, but its prevention against NASH is unclear. This study aims to investigate the preventive bioactivities of SS monomer (SS\u2010A<jats:sub>2<\/jats:sub>) against NASH and further clarify its mechanism by targeting the BAs and gut microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>The methionine and choline deficient (MCD) diet\u2010fed male C57BL\/6 mice were intervened with obeticholic acid or SS\u2010A<jats:sub>2<\/jats:sub> for 16 weeks. Hepatic pathology is assessed by hematoxylin\u2010eosin and Masson's trichrome staining. BAs in serum, liver, and colon are measured by ultra\u2010performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC\u2010TQMS). Gut microbiota in caecum are determined by 16S rDNA amplicon sequencing. In the MCD diet\u2010induced NASH mice, SS\u2010A<jats:sub>2<\/jats:sub> significantly reduces hepatic steatosis, lobular inflammation, ballooning, nonalcoholic fatty liver disease activity score (NAS) scores, and fibrosis, decreases <jats:italic>Erysipelotrichaceae (Faecalibaculum)<\/jats:italic> and <jats:italic>Lactobacillaceae (Lactobacillus)<\/jats:italic> and increases <jats:italic>Desulfovibrionaceae (Desulfovibrio)<\/jats:italic>. Moreover, SS\u2010A<jats:sub>2<\/jats:sub> reduces serum BAs accumulation and promotes fecal BAs excretion. SS\u2010A<jats:sub>2<\/jats:sub> changes the BAs profiles in both liver and serum and specifically increases the taurohyodeoxycholic acid (THDCA) level. <jats:italic>Faecalibaculum<\/jats:italic> is negatively correlated with serum THDCA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SS\u2010A<jats:sub>2<\/jats:sub> alleviates steatohepatitis possibly through regulating BAs and gut microbiota in the MCD diet\u2010induced NASH mice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202100067","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T12:04:20Z","timestamp":1622203460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Soyasaponin A<sub>2<\/sub> Alleviates Steatohepatitis Possibly through Regulating Bile Acids and Gut Microbiota in the Methionine and Choline\u2010Deficient (MCD) Diet\u2010induced Nonalcoholic Steatohepatitis (NASH) Mice"],"prefix":"10.1002","volume":"65","author":[{"given":"Fei","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health Southern Medical University  Guangzhou Guangdong 510515 P. 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