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Published on: September 6, 2024
Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched
Ivan K S Yap1, Manya Angley, Kirill A Veselkov
1Biomolecular Medicine, Division of Surgery and Cancer, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London, United Kingdom.
Insights
Autism is linked to altered metabolism, with unique urinary profiles in children. These findings reveal changes in nicotinic acid, amino acid, and gut microbial metabolite pathways, offering potential for monitoring interventions.
Area of Science:
- Biochemistry
- Metabolomics
- Developmental Neuroscience
Background:
- Autism Spectrum Disorder (ASD) is a neurodevelopmental condition impacting social behavior, often accompanied by metabolic abnormalities.
- Previous research suggests metabolic dysregulation may play a role in ASD pathogenesis and presentation.
Purpose of the Study:
- To characterize urinary metabolic phenotypes in children with autism compared to siblings and healthy controls.
- To identify novel metabolic biomarkers associated with autism.
Main Methods:
- Utilized proton nuclear magnetic resonance ((1)H NMR) spectroscopy and pattern recognition techniques.
- Analyzed urinary samples from autistic children (n=39), their nonautistic siblings (n=28), and age-matched healthy controls (n=34).
- Performed multivariate statistical analysis to compare metabolic profiles between groups.
Main Results:
- Identified increased urinary excretion of N-methyl-2-pyridone-5-carboxamide, N-methyl nicotinic acid, and N-methyl nicotinamide, indicating altered tryptophan-nicotinic acid metabolism.
- Observed significant differences in urinary glutamate and taurine levels, with autistic children showing lower glutamate and higher taurine, suggesting sulfur and amino acid metabolism perturbations.
- Detected distinct metabolic phenotype (metabotype) differences linked to mammalian-microbial cometabolites, including dimethylamine, hippurate, and phenyacetylglutamine.
Conclusions:
- Autism is associated with significant perturbations in nicotinic acid, amino acid, and gut microbial metabolite pathways.
- These urinary metabolic differences may reflect gut microbiota dysbiosis and gastrointestinal dysfunction in autistic individuals.
- The identified metabolic signatures could serve as potential biomarkers for monitoring therapeutic interventions in autism.
Abstract:
Autism is an early onset developmental disorder with a severe life-long impact on behavior and social functioning that has associated metabolic abnormalities. The urinary metabolic phenotypes of individuals (age range=3-9 years old) diagnosed with autism using the DSM-IV-TR criteria (n = 39; male = 35; female = 4), together with their nonautistic siblings (n = 28; male = 14; female = 14) and age-matched healthy volunteers (n = 34, male = 17; female = 17) have been characterized for the first time using (1)H NMR spectroscopy and pattern recognition methods. Novel findings associated with alterations in nicotinic acid metabolism within autistic individuals showing increased urinary excretion of N-methyl-2-pyridone-5-carboxamide, N-methyl nicotinic acid, and N-methyl nicotinamide indicate a perturbation in the tryptophan-nicotinic acid metabolic pathway. Multivariate statistical analysis indicated urinary patterns of the free amino acids, glutamate and taurine were significantly different between groups with the autistic children showing higher levels of urinary taurine and a lower level of urinary glutamate, indicating perturbation in sulfur and amino acid metabolism in these children. Additionally, metabolic phenotype (metabotype) differences were observed between autistic and control children, which were associated with perturbations in the relative patterns of urinary mammalian-microbial cometabolites including dimethylamine, hippurate, and phenyacetylglutamine. These biochemical changes are consistent with some of the known abnormalities of gut microbiota found in autistic individuals and the associated gastrointestinal dysfunction and may be of value in monitoring the success of therapeutic interventions.
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