Ozone and PM2.5 co-exposure exacerbates allergic rhinitis and is associated with PPAR/TRPV1-related barrier damage: Insights from nasal transcriptomics and microbiomics.

Ozone (O3) and PM2.5 are major global air pollutants that individually worsen allergic respiratory diseases, yet their combined effect on allergic rhinitis (AR) is unclear. Therefore, this study aimed to explore the aggravating effect of co-exposure to O3 and PM2.5 in AR mice and to investigate the underlying mechanisms. We established an AR model in C57BL/6J mice, which were then exposed to O3 or/and PM2.5. The mice were randomized into five groups: PBS control group, AR group, AR_O3 group, AR_PM2.5 group and AR_PM2.5_O3 group. The rhinitis symptoms were investigated and the nasal mucosal barrier injury was observed by HE and IHC. Serum biomarkers (OVA-sIgE, IL-1β, TNF-α) were examined by ELISA. Transcriptomic sequencing and 16S rRNA sequencing were conducted to analyze the changes of mRNA profiles and microbes in nasal mucosa. This study employed acute high-dose exposures to elucidate mechanistic pathways and was not designed to directly model environmental exposures. Co-exposure to O3 and PM2.5 markedly aggravated sneezing, disrupted mucosal integrity and decreased ZO-1/occludin expression. Multi-omics analysis revealed that the combined toxicity was associated with altered PPAR/TRPV1 signaling pathways. Further correlation analyses indicated crosstalk among microbiota dysbiosis, inflammatory responses and mucosal injury. In summary, our findings illustrated that co-exposure to O3 and PM2.5 exacerbates AR in mice, likely through disruption of PPAR/TRPV1 signaling and induction of nasal microbial dysbiosis.