Bacterial extracellular vesicles in colorectal cancer: mechanisms, biomarker potential, and therapeutic engineering

Colorectal cancer (CRC) is a leading cause of cancer-related deaths. The human colon, which hosts a vast and complex microbial ecosystem, plays a crucial role in health and disease, with approximately 20% of human cancers linked to microbial dysbiosis. Bacterial extracellular vesicles (BEVs) serve as critical mediators of host-microbe communication, influencing both physiological and pathological processes. In this narrative review study, we surveyed the literature published on the multifaceted roles of BEVs, derived from various bacterial strains, in the pathogenesis and treatment of CRC, using databases such as Google Scholar, Scopus, ScienceDirect, PubMed, and Web of Science. BEVs carry a diverse cargo, including proteins, nucleic acids, toxins, and signaling molecules, that can traverse host barriers, modulate immune responses, and influence cancer progression. Their biogenesis varies by bacterial type, involving complex processes such as membrane blebbing, autolysin-mediated wall weakening, and explosive cell lysis. BEVs can suppress tumor growth, positioning them as promising candidates for innovative cancer therapies. Moreover, engineered BEVs have the potential to serve as sophisticated drug delivery vehicles for chemotherapeutic or photothermal agents, as well as novel vaccine platforms. Although tumor regression and enhanced T-cell responses mediated by BEVs have been demonstrated in numerous preclinical studies, their clinical translation remains challenging. In this review, we provide a comprehensive overview of BEVs derived from diverse bacterial strains, focusing on their roles in CRC pathogenesis and therapy, while highlighting key barriers to their clinical applications. While promising, challenges remain in standardizing isolation, ensuring safety, and optimizing tumor-targeting efficiency for clinical translation. Future research focusing on advanced engineering and rigorous validation is crucial to harness the full therapeutic potential of BEVs in CRC management.