Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal (GI) dysfunction, and altered gut microbiome compositions. We sought to better understand non-behavioral features of ASD by determining molecular signatures in peripheral tissues. Herein, we present the untargeted metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing (TD) controls. Differences in lipid, amino acid, and xenobiotic metabolism discriminate ASD and TD samples. We reveal correlations between specific metabolite profiles and clinical behavior scores, and identify metabolites particularly associated with GI dysfunction in ASD. These findings support a connection between GI physiology, metabolism, and complex behavioral traits, and may advance discovery and development of molecular biomarkers for ASD.