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Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism / F. GEVI in Molecular Autism, 7 (2016)
[article]
Titre : Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism Type de document : Texte imprimé et/ou numérique Auteurs : F. GEVI, Auteur ; L. ZOLLA, Auteur ; S. GABRIELE, Auteur ; A. M. PERSICO, Auteur Article en page(s) : 47p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/complications/diagnosis/urine Biomarkers/urine Case-Control Studies Child Child, Preschool Chromatography, High Pressure Liquid Coenzyme A/urine Dysbiosis/complications/diagnosis/urine Female Humans Hydrophobic and Hydrophilic Interactions Indoleacetic Acids/urine Italy Kynurenic Acid/urine Male Melatonin/urine Metabolomics/methods Pantothenic Acid/urine Purines/urine Pyrimidines/urine Quinolinic Acid/urine Riboflavin/urine Tryptophan/urine Vitamin B 6/urine Xanthurenates/urine Autism Autism spectrum disorder Kynurenine Melatonin Metabolomics Purinergic signaling Quinolinic acid Serotonin Tryptophan Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is still diagnosed through behavioral observation, due to a lack of laboratory biomarkers, which could greatly aid clinicians in providing earlier and more reliable diagnoses. Metabolomics on human biofluids provides a sensitive tool to identify metabolite profiles potentially usable as biomarkers for ASD. Initial metabolomic studies, analyzing urines and plasma of ASD and control individuals, suggested that autistic patients may share some metabolic abnormalities, despite several inconsistencies stemming from differences in technology, ethnicity, age range, and definition of "control" status. METHODS: ASD-specific urinary metabolomic patterns were explored at an early age in 30 ASD children and 30 matched controls (age range 2-7, M:F = 22:8) using hydrophilic interaction chromatography (HILIC)-UHPLC and mass spectrometry, a highly sensitive, accurate, and unbiased approach. Metabolites were then subjected to multivariate statistical analysis and grouped by metabolic pathway. RESULTS: Urinary metabolites displaying the largest differences between young ASD and control children belonged to the tryptophan and purine metabolic pathways. Also, vitamin B6, riboflavin, phenylalanine-tyrosine-tryptophan biosynthesis, pantothenate and CoA, and pyrimidine metabolism differed significantly. ASD children preferentially transform tryptophan into xanthurenic acid and quinolinic acid (two catabolites of the kynurenine pathway), at the expense of kynurenic acid and especially of melatonin. Also, the gut microbiome contributes to altered tryptophan metabolism, yielding increased levels of indolyl 3-acetic acid and indolyl lactate. CONCLUSIONS: The metabolic pathways most distinctive of young Italian autistic children largely overlap with those found in rodent models of ASD following maternal immune activation or genetic manipulations. These results are consistent with the proposal of a purine-driven cell danger response, accompanied by overproduction of epileptogenic and excitotoxic quinolinic acid, large reductions in melatonin synthesis, and gut dysbiosis. These metabolic abnormalities could underlie several comorbidities frequently associated to ASD, such as seizures, sleep disorders, and gastrointestinal symptoms, and could contribute to autism severity. Their diagnostic sensitivity, disease-specificity, and interethnic variability will merit further investigation. En ligne : http://dx.doi.org/10.1186/s13229-016-0109-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328
in Molecular Autism > 7 (2016) . - 47p.[article] Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism [Texte imprimé et/ou numérique] / F. GEVI, Auteur ; L. ZOLLA, Auteur ; S. GABRIELE, Auteur ; A. M. PERSICO, Auteur . - 47p.
Langues : Anglais (eng)
in Molecular Autism > 7 (2016) . - 47p.
Mots-clés : Autism Spectrum Disorder/complications/diagnosis/urine Biomarkers/urine Case-Control Studies Child Child, Preschool Chromatography, High Pressure Liquid Coenzyme A/urine Dysbiosis/complications/diagnosis/urine Female Humans Hydrophobic and Hydrophilic Interactions Indoleacetic Acids/urine Italy Kynurenic Acid/urine Male Melatonin/urine Metabolomics/methods Pantothenic Acid/urine Purines/urine Pyrimidines/urine Quinolinic Acid/urine Riboflavin/urine Tryptophan/urine Vitamin B 6/urine Xanthurenates/urine Autism Autism spectrum disorder Kynurenine Melatonin Metabolomics Purinergic signaling Quinolinic acid Serotonin Tryptophan Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is still diagnosed through behavioral observation, due to a lack of laboratory biomarkers, which could greatly aid clinicians in providing earlier and more reliable diagnoses. Metabolomics on human biofluids provides a sensitive tool to identify metabolite profiles potentially usable as biomarkers for ASD. Initial metabolomic studies, analyzing urines and plasma of ASD and control individuals, suggested that autistic patients may share some metabolic abnormalities, despite several inconsistencies stemming from differences in technology, ethnicity, age range, and definition of "control" status. METHODS: ASD-specific urinary metabolomic patterns were explored at an early age in 30 ASD children and 30 matched controls (age range 2-7, M:F = 22:8) using hydrophilic interaction chromatography (HILIC)-UHPLC and mass spectrometry, a highly sensitive, accurate, and unbiased approach. Metabolites were then subjected to multivariate statistical analysis and grouped by metabolic pathway. RESULTS: Urinary metabolites displaying the largest differences between young ASD and control children belonged to the tryptophan and purine metabolic pathways. Also, vitamin B6, riboflavin, phenylalanine-tyrosine-tryptophan biosynthesis, pantothenate and CoA, and pyrimidine metabolism differed significantly. ASD children preferentially transform tryptophan into xanthurenic acid and quinolinic acid (two catabolites of the kynurenine pathway), at the expense of kynurenic acid and especially of melatonin. Also, the gut microbiome contributes to altered tryptophan metabolism, yielding increased levels of indolyl 3-acetic acid and indolyl lactate. CONCLUSIONS: The metabolic pathways most distinctive of young Italian autistic children largely overlap with those found in rodent models of ASD following maternal immune activation or genetic manipulations. These results are consistent with the proposal of a purine-driven cell danger response, accompanied by overproduction of epileptogenic and excitotoxic quinolinic acid, large reductions in melatonin synthesis, and gut dysbiosis. These metabolic abnormalities could underlie several comorbidities frequently associated to ASD, such as seizures, sleep disorders, and gastrointestinal symptoms, and could contribute to autism severity. Their diagnostic sensitivity, disease-specificity, and interethnic variability will merit further investigation. En ligne : http://dx.doi.org/10.1186/s13229-016-0109-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 Decreased tryptophan metabolism in patients with autism spectrum disorders / Luigi BOCCUTO in Molecular Autism, (June 2013)
[article]
Titre : Decreased tryptophan metabolism in patients with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Luigi BOCCUTO, Auteur ; Chin-Fu CHEN, Auteur ; Ayla PITTMAN, Auteur ; Cindy SKINNER, Auteur ; Heather MCCARTNEY, Auteur ; Kelly JONES, Auteur ; Barry BOCHNER, Auteur ; Roger STEVENSON, Auteur ; Charles E. SCHWARTZ, Auteur Année de publication : 2013 Article en page(s) : 10 p. Langues : Anglais (eng) Mots-clés : Autism Biomarker Tryptophan Metabolism Screening Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorders (ASDs) are relatively common neurodevelopmental conditions whose biological basis has been incompletely determined. Several biochemical markers have been associated with ASDs, but there is still no laboratory test for these conditions.METHODS:We analyzed the metabolic profile of lymphoblastoid cell lines from 137 patients with neurodevelopmental disorders with or without ASDs and 78 normal individuals, using Biolog Phenotype MicroArrays.RESULTS:Metabolic profiling of lymphoblastoid cells revealed that the 87 patients with ASD as a clinical feature, as compared to the 78 controls, exhibited on average reduced generation of NADH when tryptophan was the sole energy source. The results correlated with the behavioral traits associated with either syndromal or non-syndromal autism, independent of the genetic background of the individual. The low level of NADH generation in the presence of tryptophan was not observed in cell lines from non-ASD patients with intellectual disability, schizophrenia or conditions exhibiting several similarities with syndromal autism except for the behavioral traits. Analysis of a previous small gene expression study found abnormal levels for some genes involved in tryptophan metabolic pathways in 10 patients.CONCLUSIONS:Tryptophan is a precursor of important compounds, such as serotonin, quinolinic acid, and kynurenic acid, which are involved in neurodevelopment and synaptogenesis. In addition, quinolinic acid is the structural precursor of NAD+, a critical energy carrier in mitochondria. Also, the serotonin branch of the tryptophan metabolic pathway generates NADH. Lastly, the levels of quinolinic and kynurenic acid are strongly influenced by the activity of the immune system. Therefore, decreased tryptophan metabolism may alter brain development, neuroimmune activity and mitochondrial function. Our finding of decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs. En ligne : http://dx.doi.org/10.1186/2040-2392-4-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202
in Molecular Autism > (June 2013) . - 10 p.[article] Decreased tryptophan metabolism in patients with autism spectrum disorders [Texte imprimé et/ou numérique] / Luigi BOCCUTO, Auteur ; Chin-Fu CHEN, Auteur ; Ayla PITTMAN, Auteur ; Cindy SKINNER, Auteur ; Heather MCCARTNEY, Auteur ; Kelly JONES, Auteur ; Barry BOCHNER, Auteur ; Roger STEVENSON, Auteur ; Charles E. SCHWARTZ, Auteur . - 2013 . - 10 p.
Langues : Anglais (eng)
in Molecular Autism > (June 2013) . - 10 p.
Mots-clés : Autism Biomarker Tryptophan Metabolism Screening Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorders (ASDs) are relatively common neurodevelopmental conditions whose biological basis has been incompletely determined. Several biochemical markers have been associated with ASDs, but there is still no laboratory test for these conditions.METHODS:We analyzed the metabolic profile of lymphoblastoid cell lines from 137 patients with neurodevelopmental disorders with or without ASDs and 78 normal individuals, using Biolog Phenotype MicroArrays.RESULTS:Metabolic profiling of lymphoblastoid cells revealed that the 87 patients with ASD as a clinical feature, as compared to the 78 controls, exhibited on average reduced generation of NADH when tryptophan was the sole energy source. The results correlated with the behavioral traits associated with either syndromal or non-syndromal autism, independent of the genetic background of the individual. The low level of NADH generation in the presence of tryptophan was not observed in cell lines from non-ASD patients with intellectual disability, schizophrenia or conditions exhibiting several similarities with syndromal autism except for the behavioral traits. Analysis of a previous small gene expression study found abnormal levels for some genes involved in tryptophan metabolic pathways in 10 patients.CONCLUSIONS:Tryptophan is a precursor of important compounds, such as serotonin, quinolinic acid, and kynurenic acid, which are involved in neurodevelopment and synaptogenesis. In addition, quinolinic acid is the structural precursor of NAD+, a critical energy carrier in mitochondria. Also, the serotonin branch of the tryptophan metabolic pathway generates NADH. Lastly, the levels of quinolinic and kynurenic acid are strongly influenced by the activity of the immune system. Therefore, decreased tryptophan metabolism may alter brain development, neuroimmune activity and mitochondrial function. Our finding of decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs. En ligne : http://dx.doi.org/10.1186/2040-2392-4-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 Development of a cell-based metabolic test for the identification of individuals with autism spectrum disorder / Rini PAULY in Research in Autism Spectrum Disorders, 85 (July 2021)
[article]
Titre : Development of a cell-based metabolic test for the identification of individuals with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Rini PAULY, Auteur ; Lauren CASCIO, Auteur ; Sujata SRIKANTH, Auteur ; Kelly JONES, Auteur ; Skylar SORROW, Auteur ; Rossana CUBILLAN, Auteur ; Chin-Fu CHEN, Auteur ; Cindy SKINNER, Auteur ; Kevin CHAMPAIGNE, Auteur ; Roger E. STEVENSON, Auteur ; Charles E. SCHWARTZ, Auteur ; Luigi BOCCUTO, Auteur Article en page(s) : 101790 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD) Tryptophan Metabolism Diagnostic test Screening test Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a common neurodevelopmental condition with a tremendous impact on society and families. The biological basis of ASD has yet to be completely understood and there are no laboratory tests for this condition. Phenotype Mammalian Microarrays (PM-Ms) can distinguish patients with ASD from typically developing (TD) individuals by differential utilization of the amino acid tryptophan. By assessing several parameters of the assay utilizing customized tryptophan-containing PM-M plates, we improved the discrimination of the test, optimized test parameters, and minimized background noise by normalization while controlling for false discoveries. This improved platform can provide the first cell-based metabolic test to validate the clinical diagnosis of ASD and possibly identify individuals at risk even before the occurrence of neuro-behavioral symptoms. En ligne : https://doi.org/10.1016/j.rasd.2021.101790 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=458
in Research in Autism Spectrum Disorders > 85 (July 2021) . - 101790[article] Development of a cell-based metabolic test for the identification of individuals with autism spectrum disorder [Texte imprimé et/ou numérique] / Rini PAULY, Auteur ; Lauren CASCIO, Auteur ; Sujata SRIKANTH, Auteur ; Kelly JONES, Auteur ; Skylar SORROW, Auteur ; Rossana CUBILLAN, Auteur ; Chin-Fu CHEN, Auteur ; Cindy SKINNER, Auteur ; Kevin CHAMPAIGNE, Auteur ; Roger E. STEVENSON, Auteur ; Charles E. SCHWARTZ, Auteur ; Luigi BOCCUTO, Auteur . - 101790.
Langues : Anglais (eng)
in Research in Autism Spectrum Disorders > 85 (July 2021) . - 101790
Mots-clés : Autism spectrum disorder (ASD) Tryptophan Metabolism Diagnostic test Screening test Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a common neurodevelopmental condition with a tremendous impact on society and families. The biological basis of ASD has yet to be completely understood and there are no laboratory tests for this condition. Phenotype Mammalian Microarrays (PM-Ms) can distinguish patients with ASD from typically developing (TD) individuals by differential utilization of the amino acid tryptophan. By assessing several parameters of the assay utilizing customized tryptophan-containing PM-M plates, we improved the discrimination of the test, optimized test parameters, and minimized background noise by normalization while controlling for false discoveries. This improved platform can provide the first cell-based metabolic test to validate the clinical diagnosis of ASD and possibly identify individuals at risk even before the occurrence of neuro-behavioral symptoms. En ligne : https://doi.org/10.1016/j.rasd.2021.101790 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=458