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In inflammatory bowel diseases, Fusobacterium nucleatum adheres to the intestinal epithelium via adhesins such as FadA, disrupts tight junctions, and induces Toll-like receptor\u2013mediated inflammatory cascades, amplifying epithelial permeability and sustaining mucosal inflammation. In colorectal cancer, Fusobacterium nucleatum promotes carcinogenesis through multiple mechanisms, including \u03b2-catenin activation, modulation of oncogenic microRNAs, and immune evasion via Fap2\u2013TIGIT signaling, while also fostering a pro-inflammatory and immunosuppressive tumor microenvironment. Its enrichment correlates with advanced tumor stage, chemoresistance, and poor prognosis, underscoring its potential as a biomarker and therapeutic target. Beyond the gut, Fusobacterium nucleatum has been detected in atherosclerotic plaques and endocardial tissues, where it contributes to endothelial dysfunction, foam cell formation, oxidative stress, and plaque instability, thereby linking chronic oral infection with cardiovascular risk. Collectively, evidence suggests that Fusobacterium nucleatum acts as a pathophysiological connector across IBD, CRC, and CVD through conserved mechanisms of adhesion, immune modulation, and inflammation. Understanding these processes provides opportunities for innovative interventions, ranging from targeted antimicrobials and host-directed therapies to dietary and microbiome-based strategies, aimed at mitigating the systemic burden of this organism and improving clinical outcomes across multiple diseases.<\/jats:p>","DOI":"10.3390\/cancers17203348","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T07:33:50Z","timestamp":1760686430000},"page":"3348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Fusobacteriumnucleatum: Pathophysiological and Clinical Involvement in Inflammatory Bowel Diseases, Colorectal Cancer and Cardiovascular Diseases"],"prefix":"10.3390","volume":"17","author":[{"given":"Vincenzo","family":"Quagliariello","sequence":"first","affiliation":[{"name":"Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. 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