Bacterial extracellular vesicles as central mediators of microbiota-host communication

Bacterial extracellular vesicles (BEVs) are nanoscale, lipid bilayer-enclosed structures released by both Gram-negative and Gram-positive bacteria that act as active mediators of microbial and host-microbe communication rather than simple byproducts of membrane turnover. By packaging proteins, nucleic acids, lipids, and metabolites, BEVs participate in quorum sensing, biofilm regulation, horizontal gene transfer, and immune modulation, with functional outcomes that depend strongly on microbial origin and environmental context: pathogen-derived BEVs frequently promote inflammation and tissue damage, whereas commensal- and probiotic-derived BEVs are more often linked to epithelial protection and immune regulation. These properties have positioned BEVs as promising translational tools for biomarker discovery, vaccine development, and engineered drug delivery. However, vesicle heterogeneity, inconsistent isolation and purification methods, and an incomplete understanding of in vivo behavior continue to limit reproducibility and slow clinical translation. Here, we synthesize current evidence on BEV biogenesis, cargo selection, and biological function, and outline the methodological and translational challenges that must be addressed to establish BEVs as a validated interface between microbial activity and host physiology.