Urinary Tryptophan Metabolites, Trace Element Status, and Autism Spectrum Disorder: An Integrated Metabolomics–Elementomics Study in Children

Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with metabolic and environmental factors. We investigated associations between urinary tryptophan-pathway metabolites and essential/toxic trace elements in children with ASD and healthy controls. In a cross-sectional cohort of 216 children (149 ASD, 67 controls), urinary tryptophan metabolites were quantified by LC–MS/MS and normalized to creatinine. Trace elements were assessed by ICP–MS. Matching yielded 1:1 (n = 57/57) and 1:2 (n = 30/60) age- and sex-matched subsets. Correlations (Pearson or Spearman, FDR-adjusted) and group comparisons were performed; autism severity (CARS) was analyzed within ASD. Creatinine-normalized tryptamine, 5-hydroxyindoleacetic acid, and N-acetyltryptophan showed moderate, positive correlations with essential elements (Mg, Zn, Se; r ≈ 0.5-0.7; N-acetyltryptophan and IAA correlated modestly with toxic elements (Tl, Cs; r ≈ 0.3-0.4). Group differences in individual metabolites and elements were modest; however, the composite toxic element index was significantly lower in ASD ( P = .002). CARS scores did not show robust, FDR-corrected associations. Essential trace elements are closely linked to tryptophan metabolism, suggesting cofactor-dependent modulation in ASD. N-acetyltryptophan may serve as a sensor for specific toxic elements. Intervention studies are warranted to clarify causality.