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The taxon-based classical driver-passenger model, while conceptually useful, may benefit from incorporating the underlying mechanisms of microbial participation and the functional complexity of taxa contributions across CRC stages. In particular, the same taxa may exert distinct effects across carcinogenesis, and individual metabolic pathways frequently mediate multiple and divergent host responses. To address these limitations, we re-examine the roles of CRC-associated microbiota through the lens of individual virulence factor effects on the host, demonstrating their functional pleiotropy, and propose an expanded driver-passenger model. This approach highlights the central role of the virulome in CRC initiation, promotion and progression. By shifting the analytical focus from taxonomy to function, the proposed framework enables improved causality assessment and supports the development of stage-specific diagnostic and prognostic markers, as well as more targeted microbiome-directed therapeutic strategies.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1858868","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:37:23Z","timestamp":1784007443000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Virulome over taxonomy: refining the driver-passenger model in colorectal carcinogenesis"],"prefix":"10.3389","volume":"16","author":[{"given":"Evgeniya","family":"Glazunova","sequence":"first","affiliation":[{"name":"Federal State Budgetary Institution (Centre for Strategic Planning and Management of Biomedical Health Risks) of the Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kurnosov","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Institution (Centre for Strategic Planning and Management of Biomedical Health Risks) of the Federal Medical Biological Agency","place":["Moscow, Russia"]},{"name":"Emanuel Institute of Biochemical Physics of Russian Academy of Sciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Bogacheva","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Institution (Centre for Strategic Planning and Management of Biomedical Health Risks) of the Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Makarov","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Institution (Centre for Strategic Planning and Management of Biomedical Health Risks) of the Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Zlobovskaya","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Institution (Centre for Strategic Planning and Management of Biomedical Health Risks) of the Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.chom.2016.07.006","article-title":"Fap2 mediates Fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed Gal-GalNAc","volume":"20","author":"Abed","year":"2016","journal-title":"Cell Host Microbe"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3332\/ecancer.2018.865","article-title":"Colorectal carcinogenesis: an archetype of gut microbiota\u2013host interaction","volume":"12","author":"Alexander","year":"2018","journal-title":"ecancermedicalscience"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1128\/JB.184.7.1880-1887.2002","article-title":"Identification of the cAD1 sex pheromone precursor in Enterococcus faecalis","volume":"184","author":"An","year":"2002","journal-title":"J. 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