Bacterial outer membrane vesicles in colorectal cancer: interdomain communication hubs in pathogenesis and immunotherapy.

The complex interaction between the intestinal microbiota and host mucosal immunity plays a defining role in colorectal cancer (CRC) development and therapeutic outcomes. Recently, bacterial outer membrane vesicles (OMVs) - nano-sized, lipid-bilayered extracellular particulates released by both commensal and pathogenic microorganisms - have emerged as critical long-range signalling vehicles within the gut. This review provides a comprehensive synthesis of the dual functionalities of OMVs in CRC pathogenesis and oncology. Mechanistically, pathogenic OMVs cross compromised mucosal barriers to drive horizontal gene transfer (HGT) of chimeric episomes, such as SPHINX DNAs and Bovine Meat and Milk Factors (BMMFs), thereby promoting genomic instability and neoplastic transformation. Conversely, there is a paradigm shift towards exploiting next-generation probiotic and engineered OMVs as highly tuneable therapeutic platforms. By combining cutting-edge bioengineering strategies - such as biomimetic mineralisation to neutralise local tissue acidity and chemotherapeutic packaging - these nanovectors effectively reprogram the immunosuppressive tumour microenvironment (TME). Specifically, optimised OMVs modulate macrophage polarisation from an M2 to an M1 phenotype and stimulate CXCL10-mediated CD8+ T-cell infiltration, effectively turning immunologically 'cold' tumours 'hot'. Finally, the great translational challenges regarding systemic endotoxicity, scalability, and target delivery, providing a strategic approach for the integration of OMV-based platforms into synergistic immune checkpoint inhibition regimens.