High temperature exacerbates ozone-induced airway inflammation: Implication of airway microbiota and metabolites

Short-term exposure to ozone (O3) has been associated with airway inflammation. Given that high temperature (HT) accelerates O3 production, it is of significance to determine whether co-exposure to HT exacerbates O3-induced airway inflammation. The aim of this study was to examine the possible promotive effect of HT on O3-induced airway inflammation and underlying mechanisms. Forty-eight C57BL/6 N male mice were randomly divided into four groups: filtered air (control), O3, HT, and HT + O3 (co-exposure) groups. Mice in control and O3 groups were exposed to filtered air or 1 ppm O3 at 24 °C, respectively, while mice in HT and co-exposure groups were exposed to filtered air or 1 ppm O3 at 36 °C, respectively. The exposure scenario for four groups was 4 h/d for 5 consecutive days. Bronchoalveolar lavage fluids (BALF) were collected 24 h after the last exposure and subjected to examinations of oxidative stress and inflammation biomarkers, 16S rRNA sequencing, and metabolic profiling. Lung tissues were processed for H&E histological staining. The results showed that O3 inhalation triggered oxidative stress and inflammation in the airways, which was worsen by co-exposure to HT. Further studies revealed that co-exposure to HT strengthened O3-induced decline in Firmicutes and Allobaculum in airways. Moreover, co-exposure to HT promoted O3-induced airway metabolic disorder. Spearman correlation analysis revealed correlations among microbiota dysbiosis, metabolic disorder, oxidative stress and inflammation induced by co-exposure to HT and O3. Taken together, HT exposure aggravates O3-induced airway oxidative stress and inflammation, possibly through modulation of microbiota and metabolism of the airways. [Display omitted] •HT aggravates O3-induced airway oxidative stress and inflammation.•HT aggravates O3-induced airway microbiota dysbiosis and metabolic disorder.•Airway bacterial and metabolic disorders and inflammation by HT + O3 are correlated.