Live Airway Prevotella Attenuated Diesel Exhaust-Induced Lung Injury and Neutrophil Activation via Bacterial Extracellular Vesicles

Abstract Diesel exhaust (DE), as a principal contributor to traffic-related air pollution, poses significant public and occupational health risks. The lung microbiome could be shaped by inhaled pollutants, which play a crucial role in sustaining pulmonary health. Our prior study found a lower abundance of airway Prevotella nanceiensis (P.nan.) in DE-exposed individuals. Here, in this study, live P.nan. and its bacterial extracellular vesicles (BEVs) alleviated lung damage under inhaled DE exposure, accompanied by reduced neutrophil infiltration and activation. Notably, DE triggered lipid droplet accumulation in the lung, mitigated by the live P.nan./BEVs intervention. Additionally, inhibitors targeting lipid oxidation, synthesis, and transport attenuated neutrophil activation in response to diesel exhaust particle (DEP) stimulation. Moreover, the intervention of BEVs resulted in decreased levels of inflammatory mediators, neutrophil recruitment-associated chemokines, and lipid-related genes. This study highlights live P.nan./BEVs’ protective role against DE-induced lung injury, implicating neutrophil recruitment and lipid metabolism as key mechanisms and offering potential therapeutic avenues.