Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism

• DOI: 10.1186/s13229-016-0109-5
• Publication Date: 2016-11-24T04:52:22Z
• Authors: Federica Gevi; Lello Zolla; Stefano Gabriele; Antonio M. Persico
• Keywords: Tryptophan Metabolism; Purine metabolism

Autism spectrum disorder (ASD) is still diagnosed through behavioral observation, due to a lack of laboratory biomarkers, which could greatly aid clinicians in providing earlier and more reliable diagnoses. Metabolomics on human biofluids provides sensitive tool identify metabolite profiles potentially usable as biomarkers for ASD. Initial metabolomic studies, analyzing urines plasma ASD control individuals, suggested that autistic patients may share some metabolic abnormalities, despite several inconsistencies stemming from differences technology, ethnicity, age range, definition "control" status. ASD-specific urinary patterns were explored at an early 30 children matched controls (age range 2–7, M:F = 22:8) using hydrophilic interaction chromatography (HILIC)-UHPLC mass spectrometry, highly sensitive, accurate, unbiased approach. Metabolites then subjected multivariate statistical analysis grouped by pathway. Urinary metabolites displaying the largest between young belonged tryptophan purine pathways. Also, vitamin B6, riboflavin, phenylalanine-tyrosine-tryptophan biosynthesis, pantothenate CoA, pyrimidine metabolism differed significantly. preferentially transform into xanthurenic acid quinolinic (two catabolites kynurenine pathway), expense kynurenic especially melatonin. gut microbiome contributes altered metabolism, yielding increased levels indolyl 3-acetic lactate. The pathways most distinctive Italian largely overlap with those found rodent models following maternal immune activation or genetic manipulations. These results are consistent proposal purine-driven cell danger response, accompanied overproduction epileptogenic excitotoxic acid, large reductions melatonin synthesis, dysbiosis. abnormalities underlie comorbidities frequently associated ASD, such seizures, sleep disorders, gastrointestinal symptoms, contribute autism severity. Their diagnostic sensitivity, disease-specificity, interethnic variability will merit further investigation.