Exposure to ambient air pollution over developmental stages induced neurodevelopmental impairment in mice offspring via microbiome-gut-brain axis.

Exposure to air pollution has been increasingly recognized as a risk factor for neurodevelopmental disorders, and gut microbiome may play a critical role. However, current evidence still remains scarce. In the present study, mice were exposed to real-time ambient air pollution from conception through young adulthood, with neurobehavioral performance and gut microbiome being assessed across different developmental stages. Neurodevelopmental changes including emotional and cognitive impairments were observed in behavioral tests, accompanied by pathological and inflammation changes in brain, which were more pronounced in adolescence than in young adulthood. Alterations in the compositions and functions of gut microbiome were also revealed by fecal metagenomic sequencing. Mediation analysis showed that gut microbiome alterations significantly contributed to the observed neurodevelopmental changes induced by air pollution. Furthermore, after antibiotic (ABX) intervention, the observed neurobehavioral, pathological and inflammatory differences between the exposed and control groups diminished. These findings indicate that the gut microbiome mediates the neurodevelopmental damage caused by exposure to air pollution during developmental stages, adding novel insights on the underlying mechanisms linking air pollution and neurodevelopmental disorders.