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Apple cider vinegar, rich in polyphenols and organic acids, shows potential in metabolic regulation. This study aimed to investigate whether apple cider vinegar powder (ACVP) alleviates HFD-induced liver injury by modulating the gut\u2013liver axis. Methods: For 12 weeks, C57BL\/6 J mice received daily ACVP gavage while being fed a HFD. A series of biological assessments were conducted, including systemic metabolic evaluations (body weight, serum alanine aminotransferase (ALT)\/aspartate aminotransferase (AST), and lipid\/glucose levels), hepatic steatosis (hematoxylin and eosin (H&amp;E) staining), intestinal microbiome characterization (16S rRNA gene genomic analysis), and comprehensive metabolite profiling of cecal contents (non-targeted metabolomics). Pearson correlation networks integrated multi-omics data. Results: ACVP attenuated HFD-induced weight gain by 26.3%, hepatomegaly and dyslipidemia, as well as reduced hepatic lipid vacuoles and serum ALT (48%)\/AST (21.5%). ACVP restored gut microbiota diversity, enriching Muribaculaceae. Cecal metabolomics identified 38 HFD-perturbed metabolites reversed by ACVP, including indolelactate, hyocholate, and taurocholic acid. the Kyoto encyclopedia of genes and genomes (KEGG) analysis revealed ACVP-mediated recovery of linoleic acid metabolism. Correlation networks linked Akkermansia to anti-inflammatory metabolites (e.g., trans-ferulic), while Desulfobacterota correlated with pro-inflammatory oxylipins (e.g., 12,13-dihydroxy-9Z-octadecenoic acid (DHOME)). Conclusions: ACVP mitigates HFD-induced liver injury by remodeling gut microbiota, restoring microbial metabolites, and enhancing gut\u2013liver crosstalk.<\/jats:p>","DOI":"10.3390\/nu17132157","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T06:18:36Z","timestamp":1751264316000},"page":"2157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Apple Cider Vinegar Powder Mitigates Liver Injury in High-Fat-Diet Mice via Gut Microbiota and Metabolome Remodeling"],"prefix":"10.3390","volume":"17","author":[{"given":"Qiying","family":"Ding","sequence":"first","affiliation":[{"name":"Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Science and Health Engineering, Jiangnan University, Wuxi 214122, China"},{"name":"Affiliated Children\u2019s Hospital of Jiangnan University, Wuxi 214000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Xue","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Science and Health Engineering, Jiangnan University, Wuxi 214122, China"},{"name":"Affiliated Children\u2019s Hospital of Jiangnan University, Wuxi 214000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6339-8579","authenticated-orcid":false,"given":"Yilin","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi 214125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzheng","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi 214125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8514-3112","authenticated-orcid":false,"given":"Jinsong","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Science and Health Engineering, Jiangnan University, Wuxi 214122, China"},{"name":"Affiliated Children\u2019s Hospital of Jiangnan University, Wuxi 214000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghong","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Biomass Science and Engineering, Sichuan University, Chengdu 610065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8861-7686","authenticated-orcid":false,"given":"Yan","family":"Geng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Science and Health Engineering, Jiangnan University, Wuxi 214122, China"},{"name":"Affiliated Children\u2019s Hospital of Jiangnan University, Wuxi 214000, China"},{"name":"Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi 214125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41569-023-00847-5","article-title":"Obesity and the risk of cardiometabolic diseases","volume":"20","author":"Valenzuela","year":"2023","journal-title":"Nat. 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