Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder
Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder
复制标题
肠道微生物特征的改变与自闭症谱系障碍的异常代谢活动有关
DOI：
10.1080/19490976.2020.1747329
复制
发表时间：
2020-04-23
期刊：
影响因子：
12.2
通讯作者：
Liu, Xingyin
中科院分区：
文献类型：
--
作者：
Dan, Zhou;Mao, Xuhua;Liu, Xingyin
摘要自闭症谱系障碍是一种严重的神经发育障碍。为了加深对不同年龄ASD儿童肠道微生物区系结构的了解，以及肠道微生物区系与粪便代谢物之间的关系，我们首先使用16S rRNA测序方法对143名2-13岁儿童的肠道微生物群进行了评估。结果发现，ASD组α多样性随年龄增长无明显变化，而TD组α多样性随年龄增长而增加，表明ASD患者肠道微生物区系的组成发育在不同年龄段的变化与TD组不一致。最近的研究表明，慢性便秘是除ASD核心症状外，最常见的明显胃肠道(GI)症状之一。为了进一步研究ASD和GI症状之间的潜在交互作用，我们选择了30例C-ASD及其年龄匹配的TD进行元基因组学分析。我们观察到C-ASD组表现出多样性降低，苏特氏菌、普氏杆菌和类杆菌物种枯竭，以及相关的代谢活动失调，这可能参与了C-ASD的发病机制。与元基因组分析一致的是，LC/MS显示C-ASD和TD组之间的一些差异代谢物参与了神经递质的代谢网络，包括5-羟色胺、多巴胺、组氨酸和GABA。此外，我们发现代谢物的这些差异与特定细菌的丰度变化有关。这项研究提出了未来通过靶向与神经递质代谢相关的特定细菌进行ASD干预的可能方式。
ABSTRACT Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder. To enhance the understanding of the gut microbiota structure in ASD children at different ages as well as the relationship between gut microbiota and fecal metabolites, we first used the 16S rRNA sequencing to evaluate the gut microbial population in a cohort of 143 children aged 2–13 years old. We found that the α-diversity of ASD group showed no significant change with age, while the TD group showed increased α-diversity with age, which indicates that the compositional development of the gut microbiota in ASD varies at different ages in ways that are not consistent with TD group. Recent studies have shown that chronic constipation is one of the most commonly obvious gastrointestinal (GI) symptoms along with ASD core symptoms. To further investigate the potential interaction effects between ASD and GI symptoms, the 30 C-ASD and their aged-matched TD were picked out to perform metagenomics analysis. We observed that C-ASD group displayed decreased diversity, depletion of species of Sutterella, Prevotella, and Bacteroides as well as dysregulation of associated metabolism activities, which may involve in the pathogenesis of C-ASD. Consistent with metagenomic analysis, liquid chromatography-mass spectrometry (LC/MS) revealed some of the differential metabolites between C-ASD and TD group were involved in the metabolic network of neurotransmitters including serotonin, dopamine, histidine, and GABA. Furthermore, we found these differences in metabolites were associated with altered abundance of specific bacteria. The study suggested possible future modalities for ASD intervention through targeting the specific bacteria associated with neurotransmitter metabolism.