The association between inhaled tire-wear particle exposure and cognitive dysfunction in rats.

Tire wear particles (TWPs), an emerging environmental contaminant, have poorly understood impacts on cognitive function and underlying mechanisms. Herein, environmental samples from main traffic arteries were analyzed to determine TWPs concentrations, based on which Sprague-Dawley rats were allocated into control, low-TWPs, and high-TWPs exposure groups. An exposure model of TWPs was established in Sprague-Dawley rats by continuous nose and mouth inhalation of TWPs for 14 and 28 days. The experimental results demonstrated that TWPs induced multiple adverse effects in rats, primarily manifested as impaired learning and memory behavior, dysbiosis of the gut microbiota, and pathological damage accompanied by impairments in the lung, brain and hippocampal tissues. Malondialdehyde (MDA) levels were significantly elevated in both the Low and High concentration exposure groups. Gut microbiota shifts included reduced beneficial bacteria (e.g., norank_f_Ruminococcaceae, Eubacterium, Bacillus) and increased harmful bacteria (e.g., Turicibacter). Metabolomics analysis revealed altered metabolite levels and pathways linked to neurodegeneration and oxidative stress. Collectively, inhaled TWPs may alter gut microbiota and metabolome, potentially contributing to cognitive deficits.