Oral microbiome contribution in colorectal carcinogenesis: polymicrobial interactions and virulence determinants.

The contribution of the microbiome to sporadic colorectal cancer (CRC) has traditionally been interpreted through the detection of individual tumor-enriched taxa or isolated virulence factors. However, accumulating evidence indicates that CRC-associated microorganisms often act as structured polymicrobial consortia rather than as independent agents. This review proposes an expanded ecological framework for understanding the role of oral taxa in colorectal carcinogenesis. Oral bacteria, including genera Fusobacterium, Parvimonas, Peptostreptococcus, Porphyromonas, Prevotella, Streptococcus, and related taxa, may translocate to the colorectal niche through enteral or hematogenous routes and establish tumor-associated communities that partially recapitulate the structural organization and succession patterns of oral biofilms. Within these communities, Fusobacterium nucleatum serves as the primary bridging organism, facilitating interspecies adhesion and spatial organization. Parvimonas micra, Porphyromonas gingivalis, and Candida albicans display potential bridging structural and functional properties, with their roles in cooperative pathogenicity and tumor progression supported by substantial experimental evidence. We integrate three complementary conceptual frameworks: oral microbial complexes (gut co-abundance groups), bridging organisms and the extended driver-passenger model of CRC. This synthesis supports a shift from taxonomy-centered interpretation toward a functional virulome-based view, in which the role of a taxon is defined by its ecological position, interaction network, and virulence determinants. Key oral virulence factors contribute to biofilm formation, epithelial adhesion and invasion, barrier disruption, immune evasion, inflammatory modulation, metabolic remodeling of the tumor microenvironment, and metastatic potential. Because the composition of translocated oral consortia changes gradually within the colorectal niche, successive consortium members and their associated virulence determinants may serve as indirect microbial signatures of CRC progression. Recognizing CRC-associated oral communities as structured, interactive ecosystems has important diagnostic and therapeutic implications. Simultaneous detection of pathobionts, their cooperative clusters, and functionally relevant virulence determinants may improve microbiome-based risk stratification. Moreover, targeted disruption of bridging functions, interspecies interactions, or virulence factor activity may offer a precision strategy to weaken carcinogenic consortia without broad, dysbiosis-promoting antimicrobial pressure.