(LB02-10-25) The Role of Genetics and Environmental Factors in Autism Spectrum Disorder (ASD) Phenotype

Objectives: We conducted a 12-week pilot study in individuals with ASD to address the limited research on the feasibility and acceptability of personalized nutrition. We report metabolic biomarkers, chemical exposures, and genetic outcomes.

Methods: Participants followed an organic diet, took a tailored multivitamin-mineral supplement, and attended six sessions focused on food and lifestyle strategies. Blood, urine, stool, and buccal samples were collected at Weeks 0 and 12. Urine samples (50 mL) stored at -20°C were analyzed for heavy metals, nutrient elements, mycotoxins, and environmental toxins. Heavy metals were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) after sample dilution with double-distilled nitric acid and microwave-assisted digestion. Mycotoxins and environmental toxins were analyzed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Genomic sequencing was performed using high-quality DNA extraction and sequencing. All measures were compared using the Wilcoxon signed-rank test.

Results: Of the 36 participants (mean age 15±6 years; 78% male), 35 (97%) completed the study. At Week 12, cadmium (p=0.008, n=27), cesium (p=0.02, n=27), and thallium (p=0.003, n=27) increased, while tellurium (p=0.04, n=27) and sodium (p=0.05, n=27) decreased. Aflatoxin (p=0.05, n=26) and ochratoxin (p=0.0001, n=26) decreased. Others including monoethylphthalate (p=0.02, n=29), n-acetyl (3,4-dihydroxybutyl) (p < 0.0001, n=29), 2-hydroxyethyl mercapturic acid (p=0.02, n=29), and n-acetyl (carbomethyl) (p=0.02, n=29) increased, while bisphenol S decreased (p=0.05, n=29). Gene analysis showed mutations linked to neuroinflammation and detoxification, with SNPs in NLRP3, Nrf-2, IL-1β, and IL-18 genes associated with neuroinflammation.

Conclusions: Multiple factors influence ASD, including genetics, gene expression, and environmental exposures. Processed foods, contaminants, and nutrient imbalances can significantly affect gene expression and the severity of symptoms. Nutrition and lifestyle changes and reducing exposures hold promise for improving ASD.

Funding Sources: Community Health Partnerships Trailblazer Award, Indiana CTSI; Ingestive Behavioral Research Center Award, Purdue University