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This study uses multi\u2010omics data to elucidate the underlying mechanism of naringenin's reported benefit in alleviating (NASH). Male mice were fed a NASH\u2010inducing (methionine\u2010choline\u2010deficient) MCD diet with or without naringenin supplementation for 6\u2009weeks. Naringenin prevented NASH\u2010induced histopathological liver damage and reversed the abnormal levels of hepatic triglyceride (TG)\/total cholesterol (TC), serum TG\/TC, serum alanine aminotransferase\/aspartate transaminase, and hepatic malondialdehyde and glutathione. Importantly, naringenin intervention significantly modulated the relative abundance of gut microbiota and the host metabolomic profile. We detected more than 700 metabolites in the serum and found that the gut genus levels of <jats:italic>Anaeroplasma<\/jats:italic> and the <jats:italic>[Eubacterium] nodatum group<\/jats:italic> were closely associated with xanthine, 2\u2010picoline, and securinine, respectively. <jats:italic>Tuzzerella<\/jats:italic> alterations showed the highest number of associations with host endogenous metabolites such as FAHFA (8:0\/10:0), FFA (20:2), carnitine C8:1, tridecanedioic acid, securinine, acetylvaline, DL\u2010O\u2010tyrosine, and Phe\u2010Asn. This study indicates that the interplay between host serum metabolites and gut microbiota may contribute to the therapeutic effect of naringenin against NASH.<\/jats:p>","DOI":"10.1002\/fsn3.3700","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T07:10:14Z","timestamp":1695798614000},"page":"7826-7840","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Naringenin prevents non\u2010alcoholic steatohepatitis by modulating the host metabolome and intestinal microbiome in <scp>MCD<\/scp> diet\u2010fed mice"],"prefix":"10.1002","volume":"11","author":[{"given":"Peng","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Province Clinical Research Center for Precision Medicine for Critical Illness  Wuhan China"},{"name":"Hubei Key Laboratory of 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