A metabolomics approach to investigate urine levels of neurotransmitters and related metabolites in autistic children
A metabolomics approach to investigate urine levels of neurotransmitters and related metabolites in autistic children
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DOI：
10.1016/j.bbadis.2020.165859
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发表时间：
2020-10-01
影响因子：
6.2
通讯作者：
Zolla, Lello
中科院分区：
文献类型：
--
作者：
Gevi, Federica;Belardo, Antonio;Zolla, Lello
由于最近自闭症儿童的代谢异常与自闭症谱系障碍相关，本研究的目的是确定自闭症儿童尿液样本中神经递质的水平，并分析其产生过程中代谢途径的改变。因此，通过 UHPLC 质谱（Q 精确分析仪）使用非靶向代谢组学，并使用 XCMS Metlin 软件进行数据解释，在 40 名 ASD 儿童和 40 名匹配对照中探索了 ASD 特异性尿液代谢组模式。通过这种新的先进技术，与之前的研究相比，自闭症儿童中记录了更多数量的尿液改变代谢物，这使我们能够收集与神经递质产生有关的代谢物。在这些受试者中，发现大量的多巴胺和增加量的高香草酸，不利于去甲肾上腺素和肾上腺素的产生，以及发现较低的 MHPG 和香草扁桃酸。这表明多巴胺的积累并不是由于其产量增加，而是由于多巴胺β-羟化酶被4-甲酚和维生素C阻断，多巴胺生物转化为去甲肾上腺素的量减少，而这两种物质在自闭症受试者中含量很高。最后，还检测到维生素 B6 的活性形式磷酸吡哆醛 (P5P) 的量减少，该活性形式与谷氨酸生物转化为 γ-氨基丁酸 (GABA) 有关，这证明后者水平较低。所有这些改变都与自闭症受试者中特殊的肠道微生物群相关，支持微生物群-肠-脑轴的想法，然后存在神经递质水平的改变和神经元传递的改变。
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 beta-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.-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.