PM2.5 exacerbates nasal epithelial barrier damage in allergic rhinitis mice: A crosstalk between gut microbiota and NLRP3 inflammsome

Numerous studies have demonstrated a positive correlation between the frequency and severity of allergic rhinitis (AR) with fine particulate matter (PM_2.5) exposure, although the exact mechanisms remain poorly understood. This study aimed to investigate the role of gut microbiota disorder and NLRP3 pathway activation in PM_2.5-induced nasal epithelial barrier damage in AR mice. The results indicated that PM_2.5 could exacerbate rhinitis symptoms and epithelial barrier damage in nasal mucosa. The NLRP3 pathway-related proteins including NLRP3, Caspase-1, GSDMD, and IL-1β were elevated. Additionally, nasal mucosa injury was significantly worsen in AR mice with gut microbiota disorder. Gut Microbiomic studies indicated the Ileibacterium and Alistipes are associated with nasal injury exacerbation. Metabolomic analysis suggested that bile acid metabolism disorder is a potential contributor to aggravate nasal mucosa damage. The correlation analysis revealed that IL-1β was positively associated with Alistipes, Ileibacterium, cholic acid and PC (15:0/15:0). Alistipes was positively correlated with LPE18:2 and negatively correlated with zonula occludens-1 (ZO-1) and Claudin-1 proteins. In summary, gut microbiota disorder may cause abnormal bile acid metabolism and NLRP3 inflammasome activation, which participate in PM_2.5 exposure-induced exacerbation of epithelial barrier damage in nasal mucosa. This study supplied a new insight and potential targets for prevention and treatment of AR.