{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:45:43Z","timestamp":1791233143193,"version":"4.1.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The gut microbiome may significantly influence the development of colorectal cancer (CRC), with <jats:italic>Fusobacterium<\/jats:italic> species playing a key role. Recent research has identified <jats:italic>Fusobacterium animalis<\/jats:italic> as the predominant <jats:italic>Fusobacterium<\/jats:italic> species in CRC tumors. This pilot research explores the immunological and molecular interactions associated with <jats:italic>F. animalis<\/jats:italic> and other Fusobacterium species in Norwegian CRC patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tumor samples from 25 CRC patients were divided by <jats:italic>Fusobacterium<\/jats:italic> load and analyzed for molecular alterations, immunological gene expression, and macrophage polarization. <jats:italic>Fusobacterium<\/jats:italic>-high tumors were associated with microsatellite instability (MSI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Analysis of differential immune gene expression, combined with correlation analyses, identified 25 genes, including C-X-C motif chemokine ligand 8 (CXCL8), interleukin-6 (IL6), indoleamine 2,3-dioxygenase 1 (IDO1), and secreted phosphoprotein 1 (SPP1), that exhibited significant associations with <jats:italic>Fusobacterium<\/jats:italic> abundance in this cohort. Analysis of <jats:italic>Fusobacterium<\/jats:italic> adhesion protein 2 (Fap2) revealed active transcription and constitutive expression across multiple colonic sites, including CRC tumor tissues, adjacent non-neoplastic tissues, the ascending colon, and the sigmoid colon. The analysis revealed a positive correlation between RNA levels of Fusobacterium-specific genes (fap2 and nusG) and immune genes (CXCL8, IL6, SPP1, and IDO1) across different colonic sites. This suggests that the abundance of active <jats:italic>Fusobacterium<\/jats:italic> cells is related to and possibly influences the pro-inflammatory response in the colonic microenvironment. Although arginase 1 (ARG1) expression was elevated in Fusobacterium-high tumors, no significant link was found between Fusobacterium abundance and M2 macrophage polarization, contradicting previous studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>High <jats:italic>Fusobacterium<\/jats:italic>, dominated by <jats:italic>F. animalis<\/jats:italic>, was linked to increased immune gene expression and constitutive fap2 activity. M2 polarization was unaffected, possibly reflecting in vivo tumor complexity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1601423","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T05:35:45Z","timestamp":1755149745000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Fusobacterium-associated molecular and immunological alterations in colorectal cancer: Insights from a Norwegian cohort"],"prefix":"10.3389","volume":"16","author":[{"given":"Thura Akrem","family":"Omran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Subirats 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