Biomolecular Medicine, Division of Surgery and Cancer, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London, United Kingdom.
J Proteome Res. 2010 Jun 4;9(6):2996-3004. doi: 10.1021/pr901188e.
Autism is an early onset developmental disorder with a severe life-long impact on behavior and social functioning that has associated metabolic abnormalities. The urinary metabolic phenotypes of individuals (age range=3-9 years old) diagnosed with autism using the DSM-IV-TR criteria (n = 39; male = 35; female = 4), together with their nonautistic siblings (n = 28; male = 14; female = 14) and age-matched healthy volunteers (n = 34, male = 17; female = 17) have been characterized for the first time using (1)H NMR spectroscopy and pattern recognition methods. Novel findings associated with alterations in nicotinic acid metabolism within autistic individuals showing increased urinary excretion of N-methyl-2-pyridone-5-carboxamide, N-methyl nicotinic acid, and N-methyl nicotinamide indicate a perturbation in the tryptophan-nicotinic acid metabolic pathway. Multivariate statistical analysis indicated urinary patterns of the free amino acids, glutamate and taurine were significantly different between groups with the autistic children showing higher levels of urinary taurine and a lower level of urinary glutamate, indicating perturbation in sulfur and amino acid metabolism in these children. Additionally, metabolic phenotype (metabotype) differences were observed between autistic and control children, which were associated with perturbations in the relative patterns of urinary mammalian-microbial cometabolites including dimethylamine, hippurate, and phenyacetylglutamine. These biochemical changes are consistent with some of the known abnormalities of gut microbiota found in autistic individuals and the associated gastrointestinal dysfunction and may be of value in monitoring the success of therapeutic interventions.
自闭症是一种起病于早期的发育障碍，对行为和社交功能有严重的终身影响，并伴有代谢异常。本研究首次采用 (1)H NMR 光谱和模式识别方法，对符合 DSM-IV-TR 标准（n = 39；男 35 例，女 4 例）诊断为自闭症的个体（年龄范围 3-9 岁）及其非自闭症兄弟姐妹（n = 28；男 14 例，女 14 例）和年龄匹配的健康志愿者（n = 34，男 17 例，女 17 例）的尿代谢表型进行了研究。自闭症个体中烟酰胺代谢改变与烟酸代谢改变有关，表现为尿中 N-甲基-2-吡啶酮-5-甲酰胺、N-甲基烟酸和 N-甲基烟酰胺排泄增加，提示色氨酸-烟酸代谢途径受到干扰。多变量统计分析表明，氨基酸和游离氨基酸的尿液谱在各组之间存在显著差异，自闭症儿童的尿液中牛磺酸水平较高，谷氨酸水平较低，表明这些儿童的硫和氨基酸代谢受到干扰。此外，还观察到自闭症和对照组儿童之间存在代谢表型（代谢型）差异，这与哺乳动物-微生物共代谢物（包括二甲胺、马尿酸和苯乙酰谷氨酰胺）的相对尿液模式的改变有关。这些生化变化与自闭症个体中发现的一些已知的肠道微生物群异常以及相关的胃肠道功能障碍一致，可能有助于监测治疗干预的成功。
