Microbial organization, biofilm architecture, and microbiota–host interactions in colorectal and gastric cancer

Emerging evidence suggests that the relationship between the microbiome and cancer is not determined solely by microbial presence, but is also influenced by the spatial organization and functional state of microbial communities, including their organization within biofilms. In colorectal cancer (CRC), mucosal biofilms have been directly identified at the epithelial surface and associated with barrier disruption, inflammatory changes, and altered microbial–host interactions. Biofilm-associated microorganisms may additionally contribute to genotoxic, immune-modulatory, and metabolic processes, although these mechanisms are not necessarily dependent on biofilm organization. In gastric cancer (GC), Helicobacter pylori remains the primary microbial driver, while biofilm formation appears to contribute predominantly to bacterial persistence and antimicrobial tolerance, potentially prolonging chronic host–microbiota interactions. These observations illustrate that microbial organization, biofilm architecture, and organism-specific mechanisms represent distinct but interacting components of the tumor microenvironment. Importantly, detection of microbial DNA or altered microbiome composition in tumor tissues does not necessarily indicate the presence of structured biofilms, underscoring the need to distinguish tumor microbiome signals from spatially organized microbial communities. These distinctions have implications for understanding tumor-associated microbial processes and for the development of microbiome- and biofilm-targeted diagnostic and therapeutic strategies. Future studies integrating spatial imaging, multi-omics, and single-cell approaches will be essential to define the organization and functional significance of tumor-associated microbiota and clarify their contribution to cancer development and therapeutic response.