Metabolic Perturbance in Autism Spectrum Disorders: A Metabolomics Study
Abstract
Autism spectrum disorders (ASD) are a group of biological disorders with associated metabolic derangement. This study aimed to identify a pattern of metabolic perturbance in ASD using metabolomics in urinary specimens from 48 children with ASD and 53 age matched controls. Using a combination of liquid- and gas-chromatography-based mass spectrometry, we detected the levels of 82 metabolites (53 of which were increased) that were significantly altered between the ASD and the control groups using osmolality normalized data. Pattern analysis showed that the levels of several amino acids such as glycine, serine, threonine, alanine, histidine, glutamyl amino acids and the organic acid, taurine were significantly (p≤0.05) lower in ASD children. The levels of antioxidants such as carnosine were also reduced in ASD (p=0.054). Furthermore, several gut bacterial metabolites were significantly altered in ASD children who had gastrointestinal dysfunction. Overall, this study detected abnormal amino acid metabolism, increased oxidative stress, and altered gut microbiomes in ASD. The relationship of altered gut microbial co-metabolism and the disrupted metabolisms requires further investigation.
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Metabolome studies have repeatedly shown evidence of alterations in tryptophan, kynurenine, and serotonin pathways in children with ASD, including increased urinary excretion of tryptophan and associated metabolites.
“Metabolome studies have repeatedly shown evidence of alterations in tryptophan, kynurenine, and serotonin pathways in children with ASD, including reports of increased urinary excretion of tryptophan and associated metabolites [63, 67, 68, 72, 105].”
From The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders (2018) · cites this paper as [63]
Metabolomic analyses of serum, feces, and urine from ASD subjects have uncovered differences in various molecules compared to TD individuals, with many dysregulated compounds being of microbial origin.
“metabolomic analyses of serum, feces, and urine from ASD subjects have uncovered differences in various molecules compared to TD individuals, with many dysregulated compounds being of microbial origin (De Angelis et al., 2013; Kang et al., 2017a; Ming et al., 2012; Mussap et al., 2016; Wang et al., 2019).”
From Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice (2019) · cites this paper as Ming et al., 2012
ASD patients have high levels of free amino acids (FAAs), which are derived from hydrolysis of proteins and peptides; glutamate may be involved in the etiopathogenesis of neurodevelopmental disorders.
“Furthermore, ASD patients have high level of free amino acids (FAAs) [186], which are derived from hydrolysis of proteins and peptides, like glutamate that may be involved in the etiopathogenesis of neurodevelopmental disorders [187].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [186]
p-cresol and p-cresyl sulfate are phenolic compounds produced by bacteria such as C. difficile and Bifidobacterium.
“Another metabolite that we could considered is p-cresol and its co-metabolite p-cresyl sulfate, which are phenolic compounds that are produced by bacteria such as C. difficile and Bifidobacterium [185,186,187].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [186]
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References 59 · Cited by 234
- Authors
- Ming, X., Stein, T. P., Barnes, V., Rhodes, N., & Guo, L.
- Affiliations
- John F. Kennedy Medical Center (US)
- Department of Surgery, UMDNJ-School of Osteopathic Medicine, Stratford, New Jersey 08084, United States
- Colgate-Palmolive (United States) (US)
- Metabolon (United States) (US)
- Corresponding author
- Ming, Xue
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2012-11-09
- Volume
- 11
- Issue
- 12
- Pages
- 5856-5862
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- OpenAlex
- W2044459025
- Cited by
- 234
- References
- 59
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 16 · 2023: 14 · 2022: 16 · 2021: 19 · 2020: 32 · 2019: 24 · 2018: 20 · 2017: 13 · 2016: 17 · 2015: 11 · 2014: 17 · 2013: 12
- FWCI
- 6.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Proteome Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- autism spectrum disorder, urinary metabolites, amino acid metabolism, glycine, serine, threonine, alanine, histidine, taurine, carnosine, oxidative stress, gut microbiota, gastrointestinal dysfunction, children
- MeSH terms
- Adolescent, Amino Acids, Antioxidants, Bacteria, Carnosine, Child, Child Development Disorders, Pervasive, Female, Gastrointestinal Diseases, Humans, Male, Gas Chromatography-Mass Spectrometry, Severity of Illness Index, Case-Control Studies, Gastrointestinal Tract, Metagenome, Metabolomics, Metabolome
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