Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature

Zheng, Hui-Fei; Wang, Wenqiang; Li, Xinmin; Rauw, Gail; Baker, Glen B.

doi:10.1007/s00726-016-2332-y

Cited by 70 publications

(61 citation statements)

References 119 publications

(177 reference statements)

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“…Additionally, when stratified by severity of behavioral scores, we observe modest clustering according to plasma metabolites correlated to the disorder between the top and bottom quartiles of behavior severity groups for verbal, social, and ADOSS-SS metrics, but not for nonverbal, and less so with fecal samples (Figures 1N, S1H-S1I). These correlations support the involvement of lipid, amino acid, and xenobiotic metabolism in the etiology of ASD, as previously described (8,48,52), and reveal new candidates for ASD biomarkers that correlate with symptom severity.…”

Section: Global Metabolite Levels Correlate With Clinical Behavioral supporting

confidence: 87%

“…Amino acid signatures of oxidative stress and mitochondrial function are also present in our dataset. Dysregulated amino acid degradation, homeostasis, and import into the brain have been implicated as a cause of neuronal stress in ASD, and supporting metabolomic data has shown perturbations of various amino acid pathways, such as glutamate, methionine, glutathione, and gamma-glutamyl metabolites (10,17,24,26,29,33,49,52,76), which exhibit differences as well ( Figure 4E). We also demonstrate correlations between pathways of oxidative stress (cysteine, methionine, SAM and glutathione pathways) with the ADOS-SS ( Figure 4F).…”

Section: Asd Correlates With Cellular Energy and Oxidative Stress Metsupporting

confidence: 55%

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Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

Needham

Adame

Serena

et al. 2020

Preprint

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Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal (GI) dysfunction, and altered gut microbiome compositions. We sought to better understand non-behavioral features of ASD by determining molecular signatures in peripheral tissues. Herein, we present the untargeted metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing (TD) controls. Differences in lipid, amino acid, and xenobiotic metabolism discriminate ASD and TD samples. We reveal correlations between specific metabolite profiles and clinical behavior scores, and identify metabolites particularly associated with GI dysfunction in ASD. These findings support a connection between GI physiology, metabolism, and complex behavioral traits, and may advance discovery and development of molecular biomarkers for ASD. Sterol 1 1 1 Gly, Ser, Thr 0 1 1

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Section: Global Metabolite Levels Correlate With Clinical Behavioral supporting

confidence: 87%

Section: Asd Correlates With Cellular Energy and Oxidative Stress Metsupporting

confidence: 55%

Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

Needham

Adame

Serena

et al. 2020

Preprint

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“…Park et al reported that taurine, as an antioxidant and regulator of in ammation, might be a valid biomarker for ASD [46]. Combined with vitamin D3, taurine showed bene ts in the treatment of ASD [47][48]. All metabolic pathways interact with each other and constitute a complex network with related genes and diseases (Additional le 6: Fig.…”

Section: Discussionmentioning

confidence: 99%

Differential Metabolites in Chinese Autistic Children: A Multi-Centre Study Based on Urinary 1H-NMR Metabolomics Analysis

Zhou

et al. 2020

Preprint

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Background: Autism spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders. However, there is no valuable biomarker for the early diagnosis of ASD. Our large-scale and multi-centre study aims to identify metabolic variations between ASD and healthy children and to investigate differential metabolites and associated pathogenic mechanisms.Methods: 117 autistic children and 119 healthy children were recruited from research centres of 7 cities. Urine samples were assayed by 1H-NMR metabolomics analysis to detect metabolic variations. Multivariate statistical analysis, including principal component analysis (PCA) and orthogonal projection to latent structure discriminant analysis (OPLS-DA), as well as univariate analysis were used to assess differential metabolites between the ASD and control groups. The differential metabolites were further analysed by receiver operating characteristics (ROC) curve analysis and metabolic pathways analysis.Results: Compared with the control group, the ASD group showed higher levels of glycine, guanidinoacetic acid, creatine, hydroxyphenylacetylglycine, phenylacetylglycine and formate and lower levels of 3-aminoisobutanoic acid, alanine, taurine, creatinine, hypoxanthine and N-methylnicotinamide. ROC curve showed relatively significant diagnostic values for hypoxanthine (area under the curve (AUC) = 0.657, 95% CI 0.588 to 0.726), creatinine (AUC = 0.639, 95% CI 0.569 to 0.709), creatine (AUC = 0.623, 95% CI 0.552 to 0.694), N-methylnicotinamide (AUC = 0.595, 95% CI 0.523 to 0.668) and guanidinoacetic acid (AUC = 0.574, 95% CI 0.501 to 0.647) in the ASD group. Combining the metabolites creatine, creatinine and hypoxanthine, the AUC of the ROC curve reached 0.720 (95% CI 0.659 to 0.777). Significantly altered metabolite pathways associated with differential metabolites were glycine, serine and threonine metabolism, arginine and proline metabolism, and taurine and hypotaurine metabolism.Limitations: Due to the restriction of research centres, inconsistent urine collection times may have affected the quality of metabolic analyses. Moreover, it is necessary to compare metabolite levels that vary with ASD severity to better clarify the pathogenesis of ASD.Conclusions: Urinary amino acid metabolites significantly altered in children with ASD. Amino acid metabolic pathways might play important roles in the pathogenic mechanisms of ASD.Clinical Trial registration: National Study on Autism Spectrum Disorder in China (NCT02200679). Registered July 24, 2014. https://www.clinicaltrials.gov/ct2/show/NCT02200679

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“…Amino acids passing through the blood-cerebrospinal fluid barrier, such as phenylalanine, tyrosine, and tryptophan, are precursors of neurotransmitters regulating the functioning of the central nervous system that affect the emotional state and mood among others. In addition, the level of amino acids excreted with the urine provides important information about not only the dietary factors but also the factors connected with the digestive system affecting the occurrence and severity of autism symptoms [5,6]. Compounds containing a thiol group in their structure, such as homocysteine (Hcy), cysteine (Cys), glutathione (GSH), cysteinylglycine (CysGly), and γ-glutamylcysteine (γ-GluCys), play a significant role in living organisms.…”

Section: Introductionmentioning

confidence: 99%

Higher Levels of Low Molecular Weight Sulfur Compounds and Homocysteine Thiolactone in the Urine of Autistic Children

et al. 2020

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In this study, the levels of concentration of homocysteine thiolactone (HTL), cysteine (Cys), and cysteinylglycine (CysGly) in the urine of autistic and non-autistic children were investigated and compared. HTL has never been analyzed in autistic children. The levels of low molecular weight sulfur compounds in the urine of both groups were determined by validated methods based on high-performance liquid chromatography with spectrofluorometric and diode-array detectors. The statistical data show a significant difference between the examined groups. Children with autism were characterized by a significantly higher level of HTL (p = 5.86 × 10−8), Cys (p = 1.49 × 10−10) and CysGly (p = 1.06 × 10−8) in urine compared with the control group. A difference in the p-value of <0.05 is statistically significant. Higher levels of HTL, Cys, and CysGly in the urine of 41 children with autism, aged 3 to 17, were observed. The obtained results may indicate disturbances in the metabolism of methionine, Cys, and glutathione in some autistic patients. These preliminary results suggest that further research with more rigorous designs and a large number of subjects is needed.

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Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature

Cited by 70 publications

References 119 publications

Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

Differential Metabolites in Chinese Autistic Children: A Multi-Centre Study Based on Urinary 1H-NMR Metabolomics Analysis

Higher Levels of Low Molecular Weight Sulfur Compounds and Homocysteine Thiolactone in the Urine of Autistic Children

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