Urinary p-cresol in autism spectrum disorder
Urinary p-cresol in autism spectrum disorder
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DOI：
10.1016/j.ntt.2012.09.002
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Napolioni, Valerio
中科院分区：
文献类型：
--
作者：
Persico, Antonio M.;Napolioni, Valerio
自闭症谱系障碍（ASD）是一种神经精神障碍，在儿童早期发病，在大多数情况下终身后果。其特点是社会交往和沟通障碍，以及兴趣模式受限和行为定型。自闭症的病因是高度异质性的，包括大范围的遗传和环境因素。多项证据表明，除了更广泛的诊断标准和认识的提高外，还可能发生主要由于基因与环境相互作用增强而导致的真实的发病率增加。环境暴露于有机芳族化合物对甲酚（4-甲基苯酚）是相对常见的，并通过皮肤，以及胃肠道和呼吸系统发生。然而，这种化合物的最大和最广泛的来源是由一些肠道细菌代表的，这些细菌表达在人类细胞中未发现的对甲酚合成酶。在8岁以下自闭症儿童的初始样本和最近的复制样本中，发现尿对甲酚及其共轭衍生物对甲苯基硫酸盐升高，其中与女性、更大的临床严重程度（无论性别如何）和行为退化史相关。ASD中对甲酚过量的潜在来源，如肠道感染、慢性便秘、抗生素、异常肠道通透性和环境暴露正在研究中。对甲酚可能导致自闭症严重程度和肠道功能障碍恶化，通常存在于自闭症儿童中。它也可能有助于一个多生物标志物诊断面板有用的小自闭症儿童。(C)2012 Elsevier Inc. All rights reserved.
Autism spectrum disorder (ASD) is a neuropsychiatric disorder with onset during early childhood and lifelong consequences in most cases. It is characterized by impairment in social interaction and communication, as well as by restricted patterns of interest and stereotyped behaviors. The etiology of autism is highly heterogeneous, encompassing a large range of genetic and environmental factors. Several lines of evidence suggest that, in addition to broader diagnostic criteria and increased awareness, also a real increase in incidence primarily due to greater gene-environment interactions may also be occurring. Environmental exposure to the organic aromatic compound p-cresol (4-methylphenol) is relatively common and occurs through the skin, as well as the gastrointestinal and respiratory systems. However, the largest and most widespread source of this compound is represented by some gut bacteria which express p-cresol synthesizing enzymes not found in human cells. Urinary p-cresol and its conjugated derivative p-cresylsulfate have been found elevated in an initial sample and recently in a replica sample of autistic children below 8 years of age, where it is associated with female sex, greater clinical severity regardless of sex, and history of behavioral regression. Potential sources of p-cresol excess in ASD, such as gut infection, chronic constipation, antibiotics, abnormal intestinal permeability, and environmental exposure, are being investigated. P-cresol may contribute to worsen autism severity and gut dysfunction, often present in autistic children. It may also contribute to a multibiomarker diagnostic panel useful in small autistic children. (C) 2012 Elsevier Inc. All rights reserved.