The Role of Oral Pathobionts’ Outer Membrane Vesicles in Cancer Pathology and Therapeutic Development

Cancer remains one of the leading causes of mortality worldwide, with increasing recognition of the host microbiome as a modifiable contributor to tumour initiation and progression. Among microbial mediators, outer membrane vesicles (OMVs) derived from Gram-negative oral pathobionts have emerged as critical effectors of host–microbe interactions. These nanoscale vesicles function as delivery systems for a diverse range of bioactive cargo, including virulence factors, lipopolysaccharides, proteins, and nucleic acids, enabling both local and systemic modulation of host cellular processes. Emerging evidence suggests that OMVs produced by oral pathobionts, particularly Porphyromonas gingivalis and Fusobacterium nucleatum, are associated with tumour-promoting inflammation, immune dysregulation, epithelial transformation, and metastatic progression. Mechanistically, OMVs have been shown to activate key signalling pathways, disrupt mitochondrial function, induce oxidative stress, and reprogram the tumour microenvironment in ways that favour cancer cell survival and immune evasion. In addition, OMV-mediated modulation of host responses has been linked to resistance to anticancer therapies. In this review, we synthesize current evidence on the role of oral pathobionts’ OMVs in cancer biology, with a focus on their contributions to tumour initiation, progression, and metastasis. We further discuss emerging clinical associations, the potential of OMV-derived components as diagnostic biomarkers, and the growing interest in engineered OMVs as platforms for therapeutic intervention. Finally, we highlight key challenges and knowledge gaps that must be addressed to advance the translational application of OMV-based strategies in oncology. Overall, OMVs represent a promising but still evolving link between the oral microbiome and cancer, offering new insights into disease mechanisms and potential avenues for diagnosis and therapy.