Gene variations in autism spectrum disorder are associated with alteration of gut microbiota, metabolites and cytokines.
Gene variations in autism spectrum disorder are associated with alteration of gut microbiota, metabolites and cytokines.
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自闭症谱系障碍的基因变异与肠道微生物群、代谢物和细胞因子的改变有关
DOI：
10.1080/19490976.2020.1854967
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发表时间：
2021-01
期刊：
影响因子：
12.2
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Liu Z;Mao X;Dan Z;Pei Y;Xu R;Guo M;Liu K;Zhang F;Chen J;Su C;Zhuang Y;Tang J;Xia Y;Qin L;Hu Z;Liu X
肠道微生物群的遗传变异和生态失调与ASD相关。然而，在宿主遗传易感性方面，微生物群在ASD病因学中的作用仍不清楚。本研究旨在系统地探讨ASD儿童宿主遗传变异与肠道菌群之间的相互作用。应用全外显子测序技术对26例ASD患儿和26例正常对照进行单核苷酸变异（SNVs）检测。我们先前的研究揭示了该队列ASD中肠道微生物群的改变和代谢活动的紊乱。进一步进行了系统的生物信息学分析，以确定SNV与肠道微生物群及其代谢物之间的关联。ASD SNV显著富集与先天免疫应答、蛋白糖基化过程和逆行轴突运输相关的基因。这些SNV也与微生物组组成和微生物功能的广泛方面相关，特别是代谢。此外，参与神经递质代谢网络的代谢物的丰度被推断为与特定SNV和微生物有因果关系。此外，我们的数据表明，宿主遗传学和肠道微生物的相互作用可能在ASD的免疫和代谢稳态中起着至关重要的作用。本研究为探讨宿主遗传变异和肠道菌群在ASD发病机制中的相互作用提供了有价值的线索。
The genetic variations and dysbiosis of gut microbiota are associated with ASD. However, the role of the microbiota in the etiology of ASD in terms of host genetic susceptibility remains unclear. This study aims to systematically explore the interplay between host genetic variation and gut microbiota in ASD children. Whole-exon sequencing was applied to 26 ASD children and 26 matched controls to identify the single nucleotide variations (SNVs) in ASD. Our previous study revealed alteration in gut microbiota and disorder of metabolism activity in ASD for this cohort. Systematic bioinformatic analyses were further performed to identify associations between SNVs and gut microbiota, as well as their metabolites. The ASD SNVs were significantly enriched in genes associated with innate immune response, protein glycosylation process, and retrograde axonal transport. These SNVs were also correlated with the microbiome composition and a broad aspect of microbial functions, especially metabolism. Additionally, the abundance of metabolites involved in the metabolic network of neurotransmitters was inferred to be causally related to specific SNVs and microbes. Furthermore, our data suggested that the interaction of host genetics and gut microbes may play a crucial role in the immune and metabolism homeostasis of ASD. This study may provide valuable clues to investigate the interaction of host genetic variations and gut microbiota in the pathogenesis of ASD.
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DOI：
10.1093/bioinformatics/bts565
发表时间：
2012-12-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Fu L;Niu B;Zhu Z;Wu S;Li W
通讯作者：
Li W
影响因子：
4.7
作者：
Ferguson, Bradley J.;Dovgan, Kristen;Beversdorf, David Q.
通讯作者：
Beversdorf, David Q.
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
16.6
作者：
Andrews SV;Ellis SE;Bakulski KM;Sheppard B;Croen LA;Hertz-Picciotto I;Newschaffer CJ;Feinberg AP;Arking DE;Ladd-Acosta C;Fallin MD
通讯作者：
Fallin MD
影响因子：
4.2
作者：
Carter, C. J.
通讯作者：
Carter, C. J.