Bacterial outer membrane vesicles in oral diseases: from pathogenic mediators to theranostic platforms.

Bacterial outer membrane vesicles (bOMVs) are nanoscale structures derived from Gram-negative (G-) bacteria that play an important role in oral diseases. As key mediators of host-microbe interactions, bOMVs contribute to the pathogenesis of periodontitis, oral squamous cell carcinoma (OSCC), and oral lichen planus (OLP) by disrupting immune homeostasis and promoting tissue destruction. Beyond the oral cavity, bOMVs serve as critical vectors in the oral-systemic axis, disseminating virulence factors to distant organs and contributing to atherosclerotic cardiovascular diseases (ACVDs), Alzheimer's disease (AD), and gastrointestinal (GI) disorders. Concurrently, their inherent properties, including cargo-loading capacity, immunogenicity, and biofilm penetration, position them as promising platforms for noninvasive diagnostics and targeted therapeutics. This review systematically integrates current knowledge on bOMVs biogenesis, pathogenic mechanisms in oral and systemic diseases, and emerging applications in diagnosis and treatment. We also highlight key challenges and future directions for translating bOMVs-based strategies into clinical practice, emphasizing their potential as next-generation theranostic tools (combining therapeutic and diagnostic functions) for oral diseases.