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自闭症谱系障碍患者的肠道微生物群变化。

Gut microbiota changes in patients with autism spectrum disorders.

作者信息

Ding Xue, Xu Yiran, Zhang Xiaoli, Zhang Lingling, Duan Guiqin, Song Chunlan, Li Zhenghua, Yang Yanyan, Wang Yazhe, Wang Xiaoyang, Zhu Changlian

机构信息

Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, 450052, China.

Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, 450052, China.

出版信息

J Psychiatr Res. 2020 Oct;129:149-159. doi: 10.1016/j.jpsychires.2020.06.032. Epub 2020 Jul 18.

Abstract

Autism spectrum disorder (ASD) has a high incidence of intestinal comorbidity, indicating a strong association with gut microbiota. The purpose of this study was to characterize gut microbiota profiles in children with ASD. Seventy-seven children with ASD [33 with mild ASD and 44 with severe ASD according to the Childhood Autism Rating Scale score] and 50 age-matched healthy children were enrolled. Compared with children in the healthy control (HC) group, those in the ASD group showed higher biomass, richness, and biodiversity of gut microbiota, and an altered microbial community structure. At the genus level, there was a significant increase in the relative abundance of unidentified Lachnospiraceae, Clostridiales, Erysipelotrichaceae, Dorea, Collinsella, and Lachnoclostridium, whereas Bacteroides, Faecalibacterium, Parasutterella, and Paraprevotella were significantly lower in the ASD group than in the control group. The presence of unidentified Erysipelotrichaceae, Faecalibacterium, and Lachnospiraceae was positively correlated with ASD severity. Notably, three microbial markers (Faecalitalea, Caproiciproducens and Collinsella) were identified in a random forest model with an area under the curve (AUC) of 0.94 for differentiation between HCs and ASD patients. Furthermore, the validation model was consistent with the discovery set (AUC = 0.98, 95% CI: 97.9%-100%). The training and testing sets were more effective when the number of bacteria was increased. In addition, the functional properties (such as galactose metabolism, glycosyltransferase activity, and glutathione metabolism) displayed significant differences between the ASD and HC groups. The current study provides evidence for the relationship between gut microbiota and ASD, with the findings suggesting that gut microbiota could contribute to symptomology. Thus, modulation of gut microbiota may be a new therapeutic strategy for ASD.

摘要

自闭症谱系障碍(ASD)肠道共病发生率高,表明与肠道微生物群有密切关联。本研究旨在描绘ASD儿童的肠道微生物群特征。纳入了77名ASD儿童[根据儿童自闭症评定量表评分,33名轻度ASD儿童和44名重度ASD儿童]以及50名年龄匹配的健康儿童。与健康对照组(HC)儿童相比,ASD组儿童的肠道微生物群生物量、丰富度和生物多样性更高,且微生物群落结构发生改变。在属水平上,未鉴定的毛螺菌科、梭菌目、丹毒丝菌科、多雷氏菌属、柯林斯菌属和粪球菌属的相对丰度显著增加,而ASD组中拟杆菌属、粪杆菌属、副萨特氏菌属和副普雷沃氏菌属显著低于对照组。未鉴定的丹毒丝菌科、粪杆菌属和毛螺菌科的存在与ASD严重程度呈正相关。值得注意的是,在随机森林模型中鉴定出三个微生物标志物(粪栖杆菌属、产己酸菌属和柯林斯菌属),其曲线下面积(AUC)为0.94,用于区分HC组和ASD患者。此外,验证模型与发现集一致(AUC = 0.98,95%CI:97.9%-100%)。当细菌数量增加时,训练集和测试集更有效。此外,ASD组和HC组之间的功能特性(如半乳糖代谢、糖基转移酶活性和谷胱甘肽代谢)存在显著差异。本研究为肠道微生物群与ASD之间的关系提供了证据,研究结果表明肠道微生物群可能导致症状。因此,调节肠道微生物群可能是ASD的一种新治疗策略。

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