Air pollution, nasal microbiota, and bronchiolitis: understanding their interplay through a multilevel approach

Bronchiolitis is a severe acute lower respiratory tract condition in infants, with respiratory syncytial virus (RSV) infection being a leading cause. Despite extensive research, the factors influencing the severity of bronchiolitis remain poorly understood. Environmental factors, including exposure to particulate matter (PM) with diameters ≤10 μm (PM₁₀) and ≤2.5 μm (PM_2.5), are suspected of exacerbating RSV bronchiolitis by enhancing inflammatory pathways. We previously demonstrated that PM₁₀ and PM_2.5 levels during the three weeks preceding pediatric emergency department admission (the -3rd week AVG) are associated with increased bronchiolitis severity in infants. The bacterial nasal microbiota (bNM), lying at the interface between the environment and the airways, has emerged as a key modulator of host immune and inflammatory responses, potentially influencing the pathogenesis and course of bronchiolitis in response to environmental triggers. This study examines the effects of PM₁₀ and PM_2.5 on bNM composition in the context of bronchiolitis and explores the role of bacterial extracellular vesicles (bEVs) as potential modulators of inflammatory processes after PM exposure, using a zebrafish model to monitor the inflammatory response in vivo. We conducted a case-control study involving 110 infants diagnosed with bronchiolitis (cases) and 49 matched healthy controls (HC), revealing significant differences in bNM composition between cases and HC. The -3rd week average (AVG) of PM exposure influenced the bNM, with cases showing a higher relative abundance of Haemophilus influenzae (Hi), becoming more pronounced as PM levels increased. Injection of Hi-derived bEVs into zebrafish embryos induced a robust pro-inflammatory response, characterized by neutrophil recruitment and upregulation of inflammatory gene expression. Our findings reveal that air pollution alters bNM composition, potentially worsening bronchiolitis in infants through inflammatory processes. This study underscores the important role of bEVs in bronchiolitis pathogenesis, offering new insights into the interplay between environmental factors, microbiota, and host immunity in respiratory infections.