Investigating the Effects of Long-Term Fine Particulate Matter Exposure on Autism Spectrum Disorder Severity: Evidence from Multiple Analytical Approaches

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Abstract
With rapid industrial expansion, air pollution’s adverse neurological effects have gained increasing attention. Children face a greater risk of neurological damage because of their higher breathing rates, developing brains, and limited ability to detoxify harmful substances. Fine particulate matter has been identified as a primary neurotoxic contributor affecting developing brains. Strong evidence connects environmental pollutant exposure to the prevalence of Autism Spectrum Disorder (ASD), a neurodevelopmental condition marked by lasting difficulties with social communication and interaction. This study explores the association between long-term PM2.5 exposure and ASD symptom exacerbation, investigating underlying mechanisms. We hypothesize that long-term PM2.5 exposure exacerbates ASD symptoms through neuroinflammatory activation, leading to neuronal damage and impaired synaptic plasticity. Our investigation employs three complementary approaches: First, integrated analysis combining Global Burden of Disease data with Mendelian randomization demonstrates a significant association between PM2.5 exposure and increased ASD severity risk. Second, utilizing the China High-Resolution Air Pollution Database in conjunction with cohort studies, we provide evidence that ambient air pollution substantially influences autism severity, with PM2.5 identified as the predominant environmental determinant. Third, through network toxicology, single-cell transcriptomics, and animal experimentation, we demonstrate that chronic PM2.5 exposure exacerbates valproic acid-induced autism-like behaviors in murine models, identifying CTNNB1, PTEN, CCR2, AKT1, and mTOR as potential core mediating genes. Importantly, these findings represent preliminary results. Several potential confounding factors such as co-exposure to other pollutants and socioeconomic variables have not been fully addressed. While our multi-modal approach provides converging lines of evidence, further validation in larger, more diverse populations with refined control of confounders will be essential to establish causality and elucidate mechanisms. Nonetheless, these early insights advance our understanding of PM2.5-induced neurotoxicity in the context of ASD and offer timely, albeit preliminary, evidence to inform public health policy.
Funding Information
  • the Key Medical Discipline of Jiangsu Province (ZDXK202249)
  • National Natural Science Foundation of China (82371462)
  • Provincial Subsidy Funds for Pairing Assistance (DHBFZ202505)
  • Jiangsu Traditional Chinese Medicine (PDJH2024027)
  • the Qing Lan Project of Jiangsu (JS2023-27)
  • the Traditional Chinese Medicine Science and Technology Development Plan Project of Zhejiang Province (2024ZL140)
  • the Hangzhou Medical and Health Science and Technology Project (B20252321)
  • the Yangzhou Polytechnic College Research Project (2025XJ17)
  • the Social Science Research Project on Yangzhou’s Child-Friendly Initiative (2025YFE-057)
  • the Yangzhou City Basic Research Program (Joint Special Project)—Health and Wellness Category (2025-3-26, 2025-3-36)

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