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10.1186/s13229-016-0109-5 http://scihub22266oqcxt.onion/10.1186/s13229-016-0109-5 C5121959!5121959 !27904735     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27904735 &cmd=llinks): Failed to open stream: HTTP request failed! 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Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism |pdf=|usr=}}{{27904735 }} gab.com Text Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism JO: Mol Autism http://www.kidney.de/pget.php?&tw=1&pmid=27904735 #FOAvip 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 B(6), 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. Twit Text FOAVip Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism ????Mol Autism http://www.kidney.de/pget.php?&tw=1&pmid=27904735 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27904735 #FOAvip English Wikipedia <ref>{{Cite pmid|27904735 }}</ref> Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism #MMPMID27904735 Gevi F ; Zolla L ; Gabriele S ; Persico AM Mol Autism 2016[]; 7 (ä): 47 PMID27904735 show ga 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 B(6), 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. |Autism Spectrum Disorder/complications/diagnosis/*urine [MESH] |Biomarkers/urine [MESH] |Case-Control Studies [MESH] |Child [MESH] |Child, Preschool [MESH] |Chromatography, High Pressure Liquid [MESH] |Coenzyme A/urine [MESH] |Dysbiosis/complications/diagnosis/*urine [MESH] |Female [MESH] |Humans [MESH] |Hydrophobic and Hydrophilic Interactions [MESH] |Indoleacetic Acids/urine [MESH] |Italy [MESH] |Kynurenic Acid/urine [MESH] |Male [MESH] |Melatonin/urine [MESH] |Metabolomics/*methods [MESH] |Pantothenic Acid/urine [MESH] |Purines/*urine [MESH] |Pyrimidines/urine [MESH] |Quinolinic Acid/urine [MESH] |Riboflavin/urine [MESH] |Tryptophan/*urine [MESH] |Vitamin B 6/urine [MESH]Urinary metabolomics of young Italian autistic children supports abnor(epmc).pdf DeepDyve Pubget Overpricing