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However, the role of urinary microbiota and their associated OMVs proteins in the metastatic processes of bladder cancer (BCa) remains insufficiently understood. In this study, we investigated the impact of urinary microbiota on BCa progression and identified potential biomarkers within the urinary microbiome. We identified\n                    <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                    (\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    ) as a predominant member of the urinary microbiota. Proteomic analysis of\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    OMVs revealed the outer membrane protein FomA as the most abundant component. A FomA\u2010deficient\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    mutant strain was generated to assess the relationship between FomA and lymph node (LN) metastasis. Mechanistically, FomA\u2010containing OMVs directly engage Toll\u2010like receptor 2 (TLR2), triggering the NF\u2010\u03baB signaling pathway and upregulating interleukin\u20106 (IL\u20106) expression. Elevated IL\u20106 induces M2b macrophage polarization, which subsequently promotes the release of VEGF\u2010C to facilitate LN metastasis. Furthermore, we identified pinocembrin, a natural flavonoid, as a potent inhibitor of the FomA\u2013TLR2 interaction, effectively suppressing BCa progression. Collectively, our findings uncover a previously unrecognized microbiota\u2010driven mechanism by which\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    \u2010derived OMVs reprogram the tumor immune microenvironment toward a pro\u2010metastatic state and highlight FomA as a promising therapeutic target.\n                  <\/jats:p>","DOI":"10.1002\/advs.202523256","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:41:37Z","timestamp":1770972097000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["FomA\u2010Containing Outer Membrane Vesicles of\n                    <i>Fusobacterium Nucleatum<\/i>\n                    Facilitate Bladder Cancer Lymphatic Metastasis via IL\u20106\u2010Dependent M2b Macrophage Polarization"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8103-9078","authenticated-orcid":false,"given":"Wentai","family":"Shangguan","sequence":"first","affiliation":[{"name":"Department of Urology Nanfang Hospital,Southern Medical University  Guangzhou China"},{"name":"Department of Urology Second Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology Nanfang Hospital,Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxue","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology Nanfang Hospital,Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jilin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology Peking University People's Hospital  Beijing P. 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