Pollutant Burden in Autism Spectrum Disorder: Mechanistic Convergence, Genetic Susceptibility, and Clinical Translation

Vollständiger Abstract

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Autism spectrum disorder (ASD) risk reflects genetic susceptibility and modifiable environmental exposures acting during fetal and early postnatal critical periods. Building on our prior two-path model, in which folate receptor autoantibody-driven cerebral folate deficiency and oxidative stress/neuroinflammation converge on disrupted neurodevelopment, this review provides the first full mechanistic treatment of environmental pollutants within that framework. We synthesize evidence across seven exposure categories: micro/nanoplastics, plastic-associated endocrine-disrupting chemicals, ambient/indoor air pollution, tire wear particles and 6PPD-quinone, heavy metals and pesticides, industrial chemicals and persistent organic pollutants, and ultra-processed food intake as a parallel, non-pollutant contributor to the same inflammatory pathway. Human biomonitoring of micro/nanoplastics has progressed beyond detection in the placenta, brain and breast milk to direct evidence of placental genotoxicity and fetal endocrine disruption, complementing rodent data linking early-life exposure to impaired corticogenesis, disrupted microglial synaptic pruning, and ASD-relevant behavioral deficits. Across categories, oxidative stress, barrier disruption, neuroinflammation, endocrine disruption, and epigenetic modification recur as convergent mechanisms acting on trimester- and age-specific windows of vulnerability. Genetic variation in folate pathway and mitochondrial genes, as well as folate/vitamin B sufficiency, are proposed as candidate effect modifiers rather than established protective factors to modify susceptibility to this pollutant burden. Most evidence is associational or mechanistic rather than trial-based; we grade evidence strength and translate findings into biomarker-guided clinical and population-level policy guidance.