Biological properties and potential pathogenic mechanisms of oral bacterial-derived extracellular vesicles in oral and systemic diseases.

This review summarizes the biological characteristics of oral bacterial extracellular vesicles (O-BEVs) and their proposed roles in disease pathogenesis. As nanosized lipid bilayer structures secreted by oral bacteria, O-BEVs encapsulate virulence factors, nucleic acids, and metabolites, enabling them to traverse biological barriers and modulate host cellular functions. Studies suggest that O-BEVs are involved in the progression of oral diseases, including periodontitis, dental caries, and oral cancer through mechanisms such as immune activation, tissue destruction, and cellular behavior modulation. Furthermore, O-BEVs can enter the systemic circulation. Through synergistic interactions among their protein, lipid, and nucleic acid components, O-BEVs activate inflammatory pathways and compromise barrier integrity, thereby contributing to the pathogenesis of systemic diseases, including Alzheimer's disease, atherosclerosis, diabetes mellitus, rheumatoid arthritis, adverse pregnancy outcomes, and osteoporosis. However, most current evidence derives from preclinical (in vitro and animal) studies, while direct clinical evidence linking O-BEVs to human diseases remains limited, and causal relationships have not been firmly established. Understanding the mechanisms of O-BEVs may enable targeted diagnostic approches, therapies, and prevention strategies along the "oral-systemic axis", with important clinical and public health implications.