Mussap Michele, Siracusano Martina, Noto Antonio, Fattuoni Claudia, Riccioni Assia, Rajula Hema Sekhar Reddy, Fanos Vassilios, Curatolo Paolo, Barberini Luigi, Mazzone Luigi
Department of Surgical Sciences, School of Medicine, University of Cagliari, 09042 Monserrato, Italy.
Department of Biomedicine and Prevention, Tor Vergata University of Rome, 00133 Rome, Italy.
Metabolites. 2020 Nov 23;10(11):476. doi: 10.3390/metabo10110476.
Autism diagnosis is moving from the identification of common inherited genetic variants to a systems biology approach. The aims of the study were to explore metabolic perturbations in autism, to investigate whether the severity of autism core symptoms may be associated with specific metabolic signatures; and to examine whether the urine metabolome discriminates severe from mild-to-moderate restricted, repetitive, and stereotyped behaviors. We enrolled 57 children aged 2-11 years; thirty-one with idiopathic autism and twenty-six neurotypical (NT), matched for age and ethnicity. The urine metabolome was investigated by gas chromatography-mass spectrometry (GC-MS). The urinary metabolome of autistic children was largely distinguishable from that of NT children; food selectivity induced further significant metabolic differences. Severe autism spectrum disorder core deficits were marked by high levels of metabolites resulting from diet, gut dysbiosis, oxidative stress, tryptophan metabolism, mitochondrial dysfunction. The hierarchical clustering algorithm generated two metabolic clusters in autistic children: 85-90% of children with mild-to-moderate abnormal behaviors fell in cluster II. Our results open up new perspectives for the more general understanding of the correlation between the clinical phenotype of autistic children and their urine metabolome. Adipic acid, palmitic acid, and 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid can be proposed as candidate biomarkers of autism severity.
自闭症诊断正从识别常见的遗传变异转向系统生物学方法。本研究的目的是探索自闭症中的代谢紊乱，调查自闭症核心症状的严重程度是否可能与特定的代谢特征相关；并检查尿液代谢组是否能区分严重与轻度至中度的受限、重复和刻板行为。我们招募了57名2至11岁的儿童；其中31名患有特发性自闭症，26名发育正常（NT）儿童，年龄和种族相匹配。通过气相色谱 - 质谱联用（GC - MS）对尿液代谢组进行研究。自闭症儿童的尿液代谢组与NT儿童的有很大区别；食物选择性导致了进一步显著的代谢差异。严重的自闭症谱系障碍核心缺陷表现为饮食、肠道微生物失调、氧化应激、色氨酸代谢、线粒体功能障碍产生的高水平代谢物。层次聚类算法在自闭症儿童中产生了两个代谢簇：85 - 90%行为轻度至中度异常的儿童属于簇II。我们的结果为更全面理解自闭症儿童临床表型与其尿液代谢组之间的相关性开辟了新的视角。己二酸、棕榈酸和3 -（3 - 羟基苯基）- 3 - 羟基丙酸可被提议作为自闭症严重程度的候选生物标志物。
