Untargeted Metabolomic Profiling Using UHPLC-QTOF/MS Reveals Metabolic Alterations Associated with Autism

Autism spectrum disorder (ASD) is a clinical spectrum of neurodevelopment disorder characterized by deficits in social communication and social interaction along with repetitive/stereotyped behaviors. The current diagnosis for autism relies entirely on clinical evaluation and has many limitations. In this study, we aim to elucidate the potential mechanism behind autism and establish a series of potential biomarkers for diagnosis. Here, we established an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry- (UHPLC-QTOF/MS-) based metabonomic approach to discriminate the metabolic modifications between the cohort of autism patients and the healthy subjects. UHPLC-QTOF/MS analysis revealed that 24 of the identified potential biomarkers were primarily involved in amino acid or lipid metabolism and the tryptophan kynurenine pathway. The combination of nicotinamide, anthranilic acid, D-neopterin, and 7,8-dihydroneopterin allows for discrimination between ASD patients and controls, which were validated in an independent autism case-control cohort. The results indicated that UHPLC-QTOF/MS-based metabolomics is capable of rapidly profiling autism metabolites and is a promising technique for the discovery of potential biomarkers related to autism.