Oral Microbiome Activity in Children With Autism Spectrum Disorder
Oral Microbiome Activity in Children With Autism Spectrum Disorder
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DOI：
10.1002/aur.1972
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发表时间：
2018-09-01
期刊：
影响因子：
4.7
通讯作者：
Middleton, Frank A.
中科院分区：
文献类型：
--
作者：
Hicks, Steven D.;Uhlig, Richard;Middleton, Frank A.
自闭症谱系障碍（ASD）与几种口咽异常有关，包括口腔感觉敏感性、味觉和质地厌恶、言语失用症和唾液转录组改变。此外，口咽是胃肠道的唯一入口。胃肠道紊乱和胃肠道微生物组的改变是ASD的既定特征，并可能通过“微生物-肠道-大脑轴”影响行为。“大多数ASD微生物组的研究都使用了粪便样本。在这里，我们确定了2-6岁儿童唾液微生物组在三种发育特征中的变化：ASD（n = 180），非自闭症发育迟缓（DD; n = 60）和典型发育（TD; n = 106）儿童。在RNA提取和鸟枪测序后，对活跃转录的分类群进行定量，并测试组间和ASD内表型的差异。发育组之间共有12个分类群发生了变化，并确定了28个分类群，区分了有和无GI障碍的ASD患者，为肠-脑轴在ASD中的作用提供了进一步的证据。组分类的准确性进行了可视化与受试者的工作特性曲线，并验证使用50/50保持程序。五个微生物比率区分ASD与TD参与者（79.5%的准确性），三个区分ASD与DD（76.5%），三个区分ASD儿童有/无GI障碍（85.7%）。分类学途径进行了评估，使用京都基因和基因组百科全书微生物数据库，并与单因素方差分析比较，揭示能量代谢和赖氨酸降解的显着差异。总之，这些结果表明ASD中的GI微生物组破坏延伸到口咽，并表明口腔微生物组分析是评估ASD状态的潜在工具。(C)2018年国际自闭症研究学会，Wiley Periodicals，Inc。
Autism spectrum disorder (ASD) is associated with several oropharyngeal abnormalities, including buccal sensory sensitivity, taste and texture aversions, speech apraxia, and salivary transcriptome alterations. Furthermore, the oropharynx represents the sole entry point to the gastrointestinal (GI) tract. GI disturbances and alterations in the GI microbiome are established features of ASD, and may impact behavior through the "microbial-gut-brain axis." Most studies of the ASD microbiome have used fecal samples. Here, we identified changes in the salivary microbiome of children aged 2-6 years across three developmental profiles: ASD (n = 180), nonautistic developmental delay (DD; n = 60), and typically developing (TD; n = 106) children. After RNA extraction and shotgun sequencing, actively transcribing taxa were quantified and tested for differences between groups and within ASD endophenotypes. A total of 12 taxa were altered between the developmental groups and 28 taxa were identified that distinguished ASD patients with and without GI disturbance, providing further evidence for the role of the gut-brain axis in ASD. Group classification accuracy was visualized with receiver operating characteristic curves and validated using a 50/50 hold-out procedure. Five microbial ratios distinguished ASD from TD participants (79.5% accuracy), three distinguished ASD from DD (76.5%), and three distinguished ASD children with/without GI disturbance (85.7%). Taxonomic pathways were assessed using the Kyoto Encyclopedia of Genes and Genomes microbial database and compared with one-way analysis of variance, revealing significant differences within energy metabolism and lysine degradation. Together, these results indicate that GI microbiome disruption in ASD extends to the oropharynx, and suggests oral microbiome profiling as a potential tool to evaluate ASD status. (C) 2018 International Society for Autism Research, Wiley Periodicals, Inc.