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Phytochemicals soyasaponins can prevent NASH possibly by modulating GM. This study aims to investigate the preventive bioactivities of soyasaponin monomers (SS\u2010A<jats:sub>1<\/jats:sub> and SS\u2010Bb) against NASH and explores the mechanisms by targeting GM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Male C57BL\/6 mice are fed with methionine and choline deficient (MCD) diet containing SS\u2010A<jats:sub>1<\/jats:sub>, SS\u2010Bb, or not for 16 weeks. Antibiotics\u2010treated pseudo germ\u2010free (PGF) mice are fed with MCD diet containing SS\u2010A<jats:sub>1<\/jats:sub>, SS\u2010Bb, or not for 8 weeks. GM is determined by 16S rRNA amplicon sequencing. Bile acids (BAs) are measured by UPLC\u2010MS\/MS. In NASH mice, SS\u2010A<jats:sub>1<\/jats:sub> and SS\u2010Bb alleviate steatohepatitis and fibrosis, reduce ALT, AST, and LPS in serum, decrease TNF\u2010\u03b1, IL\u20106, \u03b1\u2010SMA, triglycerides, and cholesterol in liver. SS\u2010A<jats:sub>1<\/jats:sub> and SS\u2010Bb decrease <jats:italic>Firmicutes<\/jats:italic>, <jats:italic>Erysipelotrichaceae<\/jats:italic>, <jats:italic>unidentified\u2010Clostridiales<\/jats:italic>, <jats:italic>Eggerthellaceae<\/jats:italic>, <jats:italic>Atopobiaceae<\/jats:italic>, <jats:italic>Aerococcus<\/jats:italic>, <jats:italic>Jeotgalicoccus<\/jats:italic>, <jats:italic>Gemella<\/jats:italic>, <jats:italic>Rikenella<\/jats:italic>, increase <jats:italic>Proteobacteria<\/jats:italic>, <jats:italic>Verrucomicrobia<\/jats:italic>, <jats:italic>Akkermansiaceae<\/jats:italic>, <jats:italic>Romboutsia<\/jats:italic>, and <jats:italic>Roseburia<\/jats:italic>. SS\u2010A<jats:sub>1<\/jats:sub> and SS\u2010Bb alter BAs composition in liver, serum, and feces, activate farnesoid X receptor (FXR) in liver and ileum, increase occludin and ZO\u20101 in intestine. However, GM clearance abrogates the preventive bioactivities of SS\u2010A<jats:sub>1<\/jats:sub> and SS\u2010Bb against NASH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>GM plays essential roles in soyasaponin's preventive bioactivities against steatohepatitis in MCD diet\u2010induced NASH mice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202300561","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T05:08:27Z","timestamp":1705554507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Gut Microbiota Plays Essential Roles in Soyasaponin's Preventive Bioactivities against Steatohepatitis in the Methionine and Choline Deficient (MCD) Diet\u2010Induced Non\u2010Alcoholic Steatohepatitis (NASH) Mice"],"prefix":"10.1002","volume":"68","author":[{"given":"Chuhong","family":"Su","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene Guangdong Provincial Key Laboratory of Tropical Disease Research National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics School of Public Health Southern Medical University  Guangzhou Guangdong 510515 P. 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