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This study is conducted to explore the effect of GEN on metabolic dysfunction-associated steatotic liver disease (MASLD) mice. MASLD was induced in mice by a high-fat diet (HFD). The results indicated that GEN significantly reduced HFD-induced body weight and improved lipid homeostasis and glucose tolerance in HFD-fed mice. Furthermore, GEN intervention markedly ameliorated hepatic pathological changes, hepatic dysfunction, and macrophage polarization. Meanwhile, GEN had a beneficial significant impact on colonic pathological changes and the expression of tight junction-related proteins. The results of gut microbiota showed that high-dose GEN intervention was able to down-regulate Firmicutes and Proteobacteria and increase Bacteroidota at the phylum level. At the genus level, GEN intervention increased\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    ,\n                    <jats:italic>Muribaculum<\/jats:italic>\n                    , and\n                    <jats:italic>Muribaculaceae_unclassified<\/jats:italic>\n                    in MASLD mice, and decreased\n                    <jats:italic>Ruminococcus<\/jats:italic>\n                    ,\n                    <jats:italic>Allobaculum<\/jats:italic>\n                    , and\n                    <jats:italic>Helicobacter<\/jats:italic>\n                    . In conclusion, GEN attenuated lipid metabolism disorders and hepatic inflammatory reaction\n                    <jats:italic>via<\/jats:italic>\n                    regulating the composition of the gut microbiota and hepatic macrophage polarization in MASLD mice.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-27783-3","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T15:43:58Z","timestamp":1766072638000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genistein ameliorates non-alcoholic fatty liver disease in mice by modulating gut microbiota and hepatic macrophage polarization"],"prefix":"10.1038","volume":"15","author":[{"given":"Shanshan","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shomaila","family":"Mehmood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"issue":"5","key":"27783_CR1","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1007\/s43450-023-00406-6","volume":"33","author":"P Xu","year":"2023","unstructured":"Xu, P. et al. 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