Bacterial Extracellular Vesicles in Inflammatory Diseases: Emerging Roles and Mechanisms

Abstract Bacterial extracellular vesicles (BEVs), nanoscale membrane-bound particles secreted by bacteria, have emerged as pivotal mediators of host–microbe communication, particularly in the context of inflammatory diseases. By delivering diverse bioactive cargos including proteins, lipids, nucleic acids, and metabolites, BEVs orchestrate complex immunological responses, playing dual roles in both the exacerbation and resolution of inflammation. This review presents a comprehensive overview of the biogenesis, classification, and molecular composition of BEVs, with emphasis on their immunomodulatory functions. Mechanistically, BEVs derived from pathogenic bacteria can trigger robust pro-inflammatory signaling cascades, disrupt epithelial barriers, and promote tissue destruction, contributing to disease progression in conditions such as periodontitis, rheumatoid arthritis, and pulmonary disorders. Conversely, BEVs from commensal and probiotic strains exhibit anti-inflammatory and tissue-reparative effects, mediated through macrophage polarization, cytokine modulation, and gut microbiota homeostasis. Recent advances highlight the therapeutic potential of engineered BEVs as bio-nanocarriers for targeted drug delivery, vaccine platforms, and immunotherapies. We further explore the translational challenges of BEV-based strategies, including scalability, targeting specificity, and biocompatibility. By elucidating the multifaceted roles of BEVs in inflammatory pathophysiology, this review offers new insights into their application as next-generation nanotherapeutics for precision medicine.