Five-month real-ambient PM2.5 exposure impairs learning in Brown Norway rats: Insights from multi omics-based analysis

PM_2.5, recognized as a potential pathogenic factor for nervous system diseases, remains an area with many unknowns, particularly regarding its effects on human health. After five-month real-ambient PM_2.5 exposure, we observed no significant pathological damage to the lung, liver, spleen, or kidney tissues. However, PM_2.5 exposure led to neuronal degeneration in the hippocampal CA1 region of Brown Norway (BN) rats. The level of IL-6, IL-13, IL-1β, IL-12, IL-4, GRO/KC, MIP-1α, CM-CSF significantly increased in lung lavage fluid (P < 0.05 for all). Notably, we detected a slight impairment in spatial learning ability, as evidenced by the Barnes maze training outcomes. There were no significant changes in the bacterial community in lung lavage fluid (P = 0.621), but the bacterial community in the gut significantly changed (P < 0.001), with more species identified (P < 0.05). The metabolomic analysis revealed 147 and 149 significantly changed metabolites in the pulmonary system and serum, respectively (P < 0.05). PM_2.5 exposure caused a decrease in Nervonic acid (NA) in both the lung and serum, which likely contributed to spatial learning impairment (P < 0.01). The correlation between lung metabolites, gut bacterial species, and serum metabolites indicated that PM_2.5 exposure likely impaired spatial learning through the lung-gut-brain axis pathway. Lung and serum metabolic disorders and intestinal microbial imbalance occurred in BN rats post-five-month real-ambient PM_2.5 exposure. There were two potential ways that PM_2.5 exposure caused the decline of spatial learning ability in wild-type BN rats: (1) PM_2.5 exposure led to a significant decrease of neuroprotective Nervonic acid in lung and serum metabolites. (2) PM_2.5 exposure likely led to reduced spatial learning ability through the lung-gut-brain axis.