ONCOMICROBIOLOGY AND MICROBIAL GENOTOXINS:DNA DAMAGE, CARCINOGENESIS, AND COLORECTAL MICROBIOME DYNAMICS

Oncomicrobiology is an interdisciplinary field that has gained increasing attention in recent years and focuses on the roles of microorganisms in cancer development and progression. Current evidence shows that microorganisms are not merely infectious agents. It has become clear that they can actively contribute to the process of carcinogenesis through direct or indirect genotoxic effects. In this chapter, the mechanisms by which microorganisms induce DNA damage are discussed in detail. In addition, the ways in which this damage leads to genomic instability are also evaluated. Bacterial genotoxins such as colibactin, cytolethal distending toxin (CDT), and Bacteroides fragilis toxin (BFT) are known to directly induce DNA breaks and challenge cellular DNA repair mechanisms. In addition to these direct effects, indirect mechanisms including chronic inflammation, increased oxidative stress, and mitochondrial dysfunction also contribute to an increased genotoxic burden. Alterations in epigenetic regulation represent another important component of this process. In the context of colorectal cancer in particular, dysbiosis of the gut microbiota appears to play a critical role. A reduction in protective short-chain fatty acid–producing bacteria is frequently observed. In contrast, an increase in pathogenic or oral-derived microorganisms has been reported. This imbalance contributes to the disruption of epithelial barrier integrity and promotes the formation of a proinflammatory microenvironment. This chapter also addresses the contribution of microorganisms other than bacteria to carcinogenesis. Viral integration into the host genome may result in chromosomal instability. Genotoxic effects of fungal metabolites may further exacerbate this process. Protozoa, on the other hand, are known to weaken the epithelial barrier and enhance inflammatory responses. Together, these findings highlight the multifaceted roles of microorganisms in cancer biology. Microbial signatures identified at different stages of colorectal cancer are particularly noteworthy. These signatures indicate that the microbial composition changes dynamically throughout disease progression. Moreover, such changes may offer potential diagnostic and prognostic biomarkers. In conclusion, microorganisms play a role not only in the initiation of cancer but also in tumor progression, shaping of the immune microenvironment, and alterations in metabolic regulation. The available evidence suggests that microbial factors may represent important targets in cancer prevention strategies. They may also be relevant for early detection and the development of targeted therapeutic approaches. Therefore, a better understanding of host–microbiota interactions may provide new perspectives on cancer biology. Future multidisciplinary studies are expected to be crucial for translating this growing body of knowledge into clinical practice.