Metabolic Perturbance in Autism Spectrum Disorders: A Metabolomics Study

Journal of Proteome Research (Impact Factor: 4.25). 10/2012; 11(12). DOI: 10.1021/pr300910n
Source: PubMed


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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Available from: Xue Ming, Jan 28, 2015
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    • "The findings are consistent with available epidemiological studies where disruption of microbe-generated metabolites has been reported in children with comorbid presentation of gastrointestinal dysfunction and autism spectrum disorders (ASD) (Wang and Kasper, 2014; Marques et al., 2010). Reduced urinary levels of carnosine, glycine, serine, threonine, alanine and histidine have also been observed in children with ASD, suggesting an imbalance of resident gut bacteria involved in both amino acid and carbohydrate metabolism may be present (Williams et al., 2011; Ming et al., 2012). A reduced capacity for nutrient digestion and transport in children with ASD has been related to increased levels of Clostridium species, Bacteriodetes depletion, and loss of metabolites related to energy homeostastis (e.g disaccharidases, hexose transporters) (Williams et al., 2011). "
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    • "However, the role of astrocytes in ASD is not limited to regulation of neurogenesis. It is widely accepted that autistic pathology results from metabolic deregulation and toxicity (Melnyk et al., 2012; Ming et al., 2012). Chlorinated acetates, fluoxetine, ethanol, and copper are all known to disturb glucose uptake and metabolism in astrocytes (Kreft et al., 2012). "
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    • "The term ASD is used to collectively describe a group of disorders that are characterized by classical autistic symptoms, such as reduced sociability and social recognition. Recent evidence suggests, albeit in relatively small cohorts, that ASDs may be associated with alterations in microbiota composition and metabolism (Critchfield et al. 2011; de Theije et al. 2011; Douglas-Escobar et al. 2013; Gondalia et al. 2012; Louis 2012; Macfabe 2012; Ming et al. 2012; Mulle et al. 2013). In addition to these correlative findings in humans, GF mice have recently been shown to have core social deficits and increased repetitive behaviours similar to that observed in ASD (Desbonnet et al. 2013). "
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