Microbial extracellular vesicles in the lung: friends in health, agents in disease

Microbial extracellular vesicles (mEVs) are emerging as key mediators at the host-microbe interface in the lung, playing a remarkable dual role as both pathogenic drivers and therapeutic modulators. These nano-sized, membrane-bound structures (20-400 nm) secreted by bacteria, fungi, and other microorganisms carry diverse bioactive cargo including lipids, proteins, and nucleic acids that can profoundly influence host immune responses and tissue homeostasis. mEVs derived from probiotic bacteria demonstrate significant therapeutic potential as immunomodulatory agents capable of reducing pulmonary inflammation and enhancing epithelial barrier function. These probiotic-derived vesicles represent a novel class of postbiotics - bioactive microbial products that confer health benefits without requiring live microbial cells. Conversely, in pathogenic contexts, mEVs from bacteria such as Pseudomonas aeruginosa and Escherichia coli trigger robust inflammatory responses in the lung through pattern recognition receptor activation, particularly Toll-like receptors (TLRs)-2 and TLR-4, leading to upregulation of pro-inflammatory cytokines and contributing to chronic respiratory conditions including asthma and chronic obstructive pulmonary disease. Given its extensive surface area and highly specialized immune network, the lung represents a highly receptive site for mEV-mediated interactions. This review synthesizes evidence on pathogenic mechanisms of mEVs and explores their therapeutic potential in respiratory medicine, with specific focus on: (1) the role of environmentally-derived mEVs from dust and airborne sources in chronic respiratory inflammation; (2) recent experimental evidence of probiotic-derived mEVs therapeutic effects across diverse pulmonary conditions and (3) the concept of mEVs as both protective postbiotics and inflammatory triggers in the lung.