GC-MS-based urine metabolic profiling of autism spectrum disorders

Abstract

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders resulting from multiple factors. Diagnosis is based on behavioural and developmental signs detected before 3 years of age, and there is no reliable biological marker. The purpose of this study was to evaluate the value of gas chromatography combined with mass spectroscopy (GC-MS) associated with multivariate statistical modeling to capture the global biochemical signature of autistic individuals. GC-MS urinary metabolic profiles of 26 autistic and 24 healthy children were obtained by liq/liq extraction, and were or were not subjected to an oximation step, and then were subjected to a persilylation step. These metabolic profiles were then processed by multivariate analysis, in particular orthogonal partial least-squares discriminant analysis (OPLS-DA, R(2)Y(cum) = 0.97, Q(2)(cum) = 0.88). Discriminating metabolites were identified. The relative concentrations of the succinate and glycolate were higher for autistic than healthy children, whereas those of hippurate, 3-hydroxyphenylacetate, vanillylhydracrylate, 3-hydroxyhippurate, 4-hydroxyphenyl-2-hydroxyacetate, 1H-indole-3-acetate, phosphate, palmitate, stearate, and 3-methyladipate were lower. Eight other metabolites, which were not identified but characterized by a retention time plus a quantifier and its qualifier ion masses, were found to differ between the two groups. Comparison of statistical models leads to the conclusion that the combination of data obtained from both derivatization techniques leads to the model best discriminating between autistic and healthy groups of children.

Metabolic Profiling and Phenotyping of Central Nervous System Diseases: Metabolites Bring Insights into Brain Dysfunctions

“…hippurate, one of its precursors 3-hydroxyphenylacetate and co-metabolite 3-hydroxyhippurate, as well as indole-3-acetate (Emond et al 2013). These studies performed in ASD mouse models and clinical samples strongly support a recent theory involving gut microbial deregulations in neurological conditions (Collins et al 2012;Cryan and Dinan 2012).…”

Urinaryp-cresol is elevated in young French children with autism spectrum disorder: a replication study

“…Hence, dose-dependent effects of p-cresol on behavior cannot be dismissed. Finally, not only p-cresol, but also several urinary metabolites, either derived from gut bacteria or from environmental sources, result unbalanced in ASD (Emond et al, 2013;Mavel et al, 2013;Yap et al, 2010). Further metabolomic profiling of our ASD sample will thus be critical to understand whether and to what extent different combinations of gut-derived compounds including, but perhaps not limited to p-cresol, may collectively produce clinically relevant effects in ASD children from different ethnic backgrounds.…”

Autism spectrum disorders and intestinal microbiota

“…In particular, we found increased levels of 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid, cis-aconitic acid, glycolic acid, 3,4-dihydroxybutyric acid, pyroglutamic acid and erythronic acid in the urine of children with an ASD, and some of these compounds have been previously linked to autistic disorders. 45,46,47 Finally, we have demonstrated the increased excretion of tryptophan, a neurotransmitter precursor of serotonin, a brain neurotransmitter. The increased urination of tryptophan fragments correlates with increased tryptophan degradation, and this increase has been observed in psychiatric conditions such as depression, mental retardation and anxiety.…”