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Methods: To explore the impact of exercise on obesity-associated osteoarthritis (OA), rats were fed a high-fat\/high-sucrose (HFS) diet with or without exercise. Histological staining and micro-computed tomography (micro-CT) were used to assess the effects of exercise on articular cartilage and subchondral bone. 16S rRNA sequencing and Gas Chromatography\u2013Mass Spectrometry (GC-MS) were performed to analyze alteration in fecal gut microbiota and serum SCFAs. Results: Exercise prevented articular cartilage degeneration and subchondral bone loss in the HFS diet with exercise (HE) group compared to the HFS-diet control sedentary (HS) group. Gut microbiota analysis revealed that exercise reduced the relative abundances of families Lachnospiraceae, Ruminococcaceae, genera Ruminococcus, Colidextribacter, Caproiciproducens, and the unidentified genus of Lachnospiraceae, while increased the relative abundance of genus Akkermansia. Metabolomic analysis indicated exercise prevented AA reduction in the HE group. In addition, the level of AA was negatively correlated with OA severity and with the abundances of families Lachnospiraceae and Ruminococcaceae, genus Colidextribacter and the unidentified genus of Lachnospiraceae. Conclusions: Exercise effectively preserves the integrity of the cartilage\u2013subchondral bone unit. The observed modifications in gut microbiota and AA levels following exercise intervention may be associated with the protective mechanisms against obesity-associated OA.<\/jats:p>","DOI":"10.3390\/metabo16070452","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T08:45:20Z","timestamp":1782722720000},"page":"452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut\u2013Joint Axis: The Role of Exercise on Gut Microbiota and Acetic Acid Modulation in Obesity-Associated Osteoarthritis Rats"],"prefix":"10.3390","volume":"16","author":[{"given":"Ruimin","family":"Chi","sequence":"first","affiliation":[{"name":"School of Medicine and Pharmaceutical Engineering, Taizhou Vocational and Technical College, Taizhou 318000, China"},{"name":"Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6310-5307","authenticated-orcid":false,"given":"Xiaoxia","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou 318000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1669-0547","authenticated-orcid":false,"given":"Bingjin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmaceutical Engineering, Taizhou Vocational and Technical College, Taizhou 318000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1622-8985","authenticated-orcid":false,"given":"Tao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3875","DOI":"10.1007\/s10067-020-05106-3","article-title":"Can metabolic profiling provide a new description of osteoarthritis and enable a personalised medicine approach?","volume":"39","author":"Jaggard","year":"2020","journal-title":"Clin. 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