A Multi-Omics Study of Neurodamage Induced by Growth-Stage Real-Time Air Pollution Exposure in Mice via the Microbiome–Gut–Brain Axis

Air pollution has been widely recognized as a risk factor for neurological disorders, and the gut microbiome may play a mediating role. However, current evidence remains limited. In this study, a mouse model was employed with continuous exposure to real-time air pollution from conception to late adolescence. Effects of growth-stage air pollution exposure on the gut microbiome, host metabolites, and brain tissue were assessed. Pathological damage in the hippocampus and cortex was observed. Fecal metagenomic sequencing revealed alterations in both compositions and functions of the gut microbiome. Metabolic disturbances in unsaturated fatty acids and glycerophospholipids were identified in the intestine, serum, and brain tissues, with significant changes in metabolites (e.g., gamma-linolenic acid, alpha-linolenic acid, docosahexaenoic acid (DHA), phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidylserine (PS). Serum levels of the pro-inflammatory mediator leukotriene C4 were also elevated. Correlation analysis identified a group of different gut microbiome species that were associated with host metabolites. Furthermore, mediation analysis showed that intestinal and serum metabolites mediated the associations between the key gut microbiome and brain microbiome. These findings indicate that the metabolic crosstalk in the gut-brain axis mediates the neuronal damage in mice induced by growth-stage air pollution exposure, potentially through pathways involving lipid metabolism and inflammation.