A metabolomics approach to investigate urine levels of neurotransmitters and related metabolites in autistic children

• Published in: Biochimica et biophysica acta. Molecular basis of disease Vol. 1866; no. 10; p. 165859
• Main Authors: Gevi, Federica, Belardo, Antonio, Zolla, Lello
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2020
• Subjects: Autism; Autism Spectrum Disorder - metabolism; Autism Spectrum Disorder - physiopathology; Autism Spectrum Disorder - urine; Brain - cytology; Brain - metabolism; Brain - physiopathology; Case-Control Studies; Child; Child, Preschool; Cresols - metabolism; Cresols - urine; Dopamine; Female; Gastrointestinal Microbiome - physiology; Humans; Male; Metabolic Networks and Pathways; Metabolomics; Microbiome; Microbiota-gut-brain axis; Neurotransmitter Agents - metabolism; Neurotransmitter Agents - urine; Noradrenaline; Pyridoxal Phosphate - metabolism; Pyridoxal Phosphate - urine; Synaptic Transmission - physiology; Autism; Metabolomics; Microbiota-gut-brain axis; Dopamine; Noradrenaline; Microbiome
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2020.165859

Since recently metabolic abnormalities in autistic children have been associated with ASD disturbs, the aim of this study is to determine the neurotransmitter levels in urine samples of autistic children and to analyse the altered metabolic pathway involved in their production. Thus, ASD-specific urinary metabolomic patterns were explored in 40 ASD children and 40 matched controls using untargeted metabolomics through UHPLC-mass spectrometry (Q-exactive analyser), and by using XCMS Metlin software for data interpretation. Through this new advanced technique, a more considerable number of urinary altered metabolites were recorded in autistic children, than in the previous investigations, which allowed us to collect metabolites involved in neurotransmitter production. In these subjects, a high amount of dopamine was revealed and an increased amount of homovanillic acid, to the detriment of noradrenaline and adrenaline production, as well as MHPG and vanillylmandelic acid, which were found lower. This indicates that the accumulation of dopamine is not due to its greater production, but its lesser biotransformation into noradrenaline, due to the blockage of the dopamine β-hydroxylase enzyme by 4-cresol and vitamin C, both found in high quantities in autistic subjects. Finally, a decreased amount of the active form of vitamin B6, pyridoxal phosphate (P5P), implicated in biotransformation of glutamate into γ-aminobutyric acid (GABA), was also detected, justifying the lower levels of latter. All of these alterations are correlated with a peculiar intestinal microbiome in autistic subjects, supporting the idea of a microbiota-gut-brain axis, then altered levels of neurotransmitters and altered neuronal transmission exist. •We explored urinary metabolomic patterns in 40 ASD children and 40 matched controls trough LC-MS.•We found alterations of several metabolic pathways involved in neurotransmitter production in the urine of ASD children.•We found higher levels of dopamine, homovanillic acid, lower GABA, noradrenaline, adrenaline, MHPG and vanillylmandelic acid.•We recorded a significant amount of 4-cresol, a microbiome product, and lower synthesis of the active form of vitamin B6.•The microbiome could directly influence neuronal transmission through the gut-brain axis.