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Herein, integrated multi\u2010omics analyses of stool and blood samples from subjects from Pearl River Osteoarthritis Cohort (PROC, N = 207) are conducted to explore the potential gut\u2010joint axis. Specifically, gut metagenomics, serum metabolomics and plasma proteomics are carried out. Knee synovitis is identified by magnetic resonance imaging. A total of 87 synovitis cases are identified in PROC, which are characterized by increased\n                    <jats:italic>Firmicutes<\/jats:italic>\n                    \/\n                    <jats:italic>Bacteroidetes<\/jats:italic>\n                    (F\/B) ratio. Alterations in microbial functions of both leucine and geraniol degradation are closely associated with increased serum 3\u2010hydroxyisovaleric acid and decreased geranic acid. These perturbations are significantly correlated with F\/B ratio and down\u2010regulated plasma TWEAK. Building upon these, the potential synovial targets are explored using a synovial single\u2010cell dataset and the Nanjing Osteoarthritis Cohort (NOC, N = 22). Synovial fluid proteomics, histological analysis, and in vitro experiments with human fibroblast\u2010like synoviocytes (FLS) are conducted for NOC subjects with different synovitis grades. An upregulated TWEAK receptor is found in higher grade of synovitis. In vitro, higher TWEAK induced down\u2010regulated TWEAK receptor in FLS. The study for the first time revealed the gut\u2010joint axis in knee synovitis, providing new insight into potential targets for synovitis treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202512020","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T01:38:58Z","timestamp":1765157938000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Multi\u2010Omics Reveal the Dysregulated Gut\u2010Joint Axis in Knee Synovitis: Data from Two Osteoarthritis Studies in China"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaoshuai","family":"Wang","sequence":"first","affiliation":[{"name":"Clinical Research Centre Zhujiang Hospital, Southern Medical University  Guangzhou Guangdong 510280 China"},{"name":"Department of Biomedical Engineering The Chinese University of Hong Kong Hong Kong 999077 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