Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

ABSTRACT Background 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. Methods We sought to better understand non-behavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (LC/MS and DMS-MS) with broad panels of identified metabolites. Herein, we present the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing (TD) controls. Results Differences in amino acid, lipid, and xenobiotic metabolism discriminate ASD and TD samples. Our results implicate oxidative stress and mitochondrial dysfunction, hormone level elevations, lipid profile changes, and altered levels of phenolic microbial metabolites. We also reveal correlations between specific metabolite profiles and clinical behavior scores. Furthermore, a summary of metabolites modestly associated with GI dysfunction in ASD are provided, and a pilot study of metabolites that can be transferred via fecal microbial transplant into mice were identified. Conclusions These findings support a connection between metabolism, GI physiology, and complex behavioral traits, and may advance discovery and development of molecular biomarkers for ASD.