Dysregulated metabolic pathways associated with air pollution exposure and the risk of autism: Evidence from epidemiological studies

Autism spectrum disorder (ASD) is a developmental disorder with symptoms that range from social and communication impairments to restricted interests and repetitive behavior and is the 4th most disabling condition for children aged 5–14. Risk factors of ASD are not fully understood. Environmental risk factors are believed to play a significant role in the ASD epidemic. Research focusing on air pollution exposure as an early-life risk factor of autism is growing, with numerous studies finding associations of traffic and industrial emissions with an increased risk of ASD. One of the possible mechanisms linking autism and air pollution exposure is metabolic dysfunction. However, there were no consensus about the key metabolic pathways and corresponding metabolite signatures in mothers and children that are altered by air pollution exposure and cause the ASD. Therefore, we performed a review of published papers examining the metabolomic signatures and metabolic pathways that are associated with either air pollution exposure or ASD risk in human studies. In conclusion, we found that dysregulated lipid, fatty acid, amino acid, neurotransmitter, and microbiome metabolisms are associated with both short-term and long-term air pollution exposure and the risk of ASD. These dysregulated metabolisms may provide insights into ASD etiology related to air pollution exposure, particularly during the perinatal period in which neurodevelopment is highly susceptible to damage from oxidative stress and inflammation.