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This study investigated the &lt;i&gt;Bacteroides eggerthii&lt;\/i&gt; therapeutic effects on MASLD by integrating multi-omics analysis and experimental validation in a Western diet (WD)-induced mouse model.Methods: Candidate strains were identified using 16S rRNA gene sequencing of fecal samples from individuals with and without MASLD or obesity. &lt;i&gt;B. eggerthii&lt;\/i&gt;, a species significantly depleted in both groups, was selected for functional evaluation. Male C57BL\/6J mice were fed a WD or WD supplemented with &lt;i&gt;B. eggerthii&lt;\/i&gt; (WD+B) for 12 weeks. Liver histology, serum biochemistry, fecal microbiome and metabolome profiling, and hepatic and intestinal transcriptomic analyses were performed. Anti-steatotic effects of &lt;i&gt;B. eggerthii&lt;\/i&gt;\u2013derived metabolites were validated &lt;i&gt;in vitro&lt;\/i&gt;.Results: &lt;i&gt;Bacteroides eggerthii&lt;\/i&gt; supplementation significantly improved liver weight, inflammation, fibrosis, and steatosis in WD+B group compared to WD alone. PICRUSt-based LEfSe analysis revealed choloylglycine hydrolase activity enrichment in gut microbiota, and strain-specific qPCR confirmed colonization in mouse colon. Integrated transcriptomic analyses revealed lipid and bile acid signaling pathway restoration, including CD36, FXR, and FGF15. Untargeted metabolomics identified elevated 2-hydroxyisocaproic acid (HICA) as a strain-derived metabolite in feces and &lt;i&gt;B. eggerthii&lt;\/i&gt; culture supernatants. &lt;i&gt;In vitro&lt;\/i&gt;, HICA significantly reduced lipid accumulation in free fatty acid-induced steatosis models.Conclusions: &lt;i&gt;Bacteroides eggerthii&lt;\/i&gt; ameliorates MASLD via gut-liver axis modulation, including bile acid metabolism and hepatic lipid signaling. These underscore its therapeutic potential and highlight HICA as a novel microbiome-derived metabolite with anti-steatotic activity.<\/jats:p>","DOI":"10.3350\/cmh.2025.0475","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T06:11:36Z","timestamp":1761631896000},"page":"239-257","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bacteroides eggerthii ameliorates metabolic dysfunction-associated steatotic liver disease through host\u2013microbe signaling and highlights 2-hydroxyisocaproate as a potential effector"],"prefix":"10.3350","volume":"32","author":[{"given":"Jiyi","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon Gyeong","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se 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