Autism diagnosis is moving from the identification of common inherited genetic variants to a systems biology approach. The aims of the study were to explore metabolic perturbations in autism, to investigate whether the severity of autism core symptoms may be associated with specific metabolic signatures; and to examine whether the urine metabolome discriminates severe from mild-to-moderate restricted, repetitive, and stereotyped behaviors. We enrolled 57 children aged 2-11 years; thirty-one with idiopathic autism and twenty-six neurotypical (NT), matched for age and ethnicity. The urine metabolome was investigated by gas chromatography-mass spectrometry (GC-MS). The urinary metabolome of autistic children was largely distinguishable from that of NT children; food selectivity induced further significant metabolic differences. Severe autism spectrum disorder core deficits were marked by high levels of metabolites resulting from diet, gut dysbiosis, oxidative stress, tryptophan metabolism, mitochondrial dysfunction. The hierarchical clustering algorithm generated two metabolic clusters in autistic children: 85-90% of children with mild-to-moderate abnormal behaviors fell in cluster II. Our results open up new perspectives for the more general understanding of the correlation between the clinical phenotype of autistic children and their urine metabolome. Adipic acid, palmitic acid, and 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid can be proposed as candidate biomarkers of autism severity.
Keywords: autism core deficits; autism spectrum disorder; food selectivity; gut dysbiosis; hierarchical clustering analysis; metabolomics.