Airway microbiota dysbiosis and metabolic disorder in ozone and PM co-exposure induced lung inflammatory injury in mice.

Co-exposure to ground-level ozone (O) and fine particles (PM, ≤ 2.5 µm in diameter) has become a primary scenario for air pollution exposure of urbanites in China. Recent studies have suggested a synergistic effect of PM and O on induction of lung inflammatory injury. However, the underlying mechanisms for respiratory toxicity induced by this co-exposure have not been adequately elucidated. In this study, a realistic exposure was based to set up the co-exposure condition of an animal model. Specifically, eighty male C57BL/6 mice (10 months old) were randomly divided into four groups: control, O, PM and co-exposure (O + PM). Mice in the co-exposure group breathed O and orally inhaled PM suspension. The scenario for O exposure was 0.6 ppm, 4 h/d, for 30 consecutive days while that for PM exposure was oral inhalation of PM suspension (5.6 mg/kg bw) once every other day and 4 h prior to O exposure. After last exposure, bronchoalveolar lavage fluids (BALF) were collected for inflammatory biomarker measurement, 16S rRNA sequencing and metabolite profiling. Lung tissues were processed for histological examination. The results demonstrated that co-exposure to O and PM exacerbated the pathological changes and inflammatory response induced by O or PM. Further studies revealed that co-exposure to O and PM increased the abundance of Prevotella in the airways and caused more severe metabolic disorders compared to O or PM exposure. Spearman correlation analysis demonstrated correlations among airway microbiota dysbiosis, metabolic disorder, inflammation, and pathological alterations induced by co-exposure to O and PM. In summary, co-exposure to O and PM worsens airway inflammatory injury, possibly through interrelated airway microbiota dysbiosis and metabolic disorder.