Novel Inter-omic Analysis Reveals Relationships Between Diverse Gut Microbiota and Host Immune Dysregulation in HLA-B27-Induced Experimental Spondyloarthritis.
Novel Inter-omic Analysis Reveals Relationships Between Diverse Gut Microbiota and Host Immune Dysregulation in HLA-B27-Induced Experimental Spondyloarthritis.
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DOI：
10.1002/art.41018
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发表时间：
2019-11
期刊：
影响因子：
--
通讯作者：
Colbert RA
中科院分区：
文献类型：
--
作者：
Gill T;Brooks SR;Rosenbaum JT;Asquith M;Colbert RA
使用新的基因组学方法确定实验性脊柱炎中与炎症相关的宿主-微生物相互作用。肠道微生物的相对频率通过16S rRNA基因测序确定，基因表达通过宿主组织的RNA-SEQ确定。研究对象为转β-B27/人HLA2-微球蛋白转基因(HLAB27TG)和野生型(WT)大鼠，分别来自Dark Agti、Lewis和Fischer背景。使用Cytoscape进行内部经济学分析以确定相关关系。PICRUST用于根据已知的元基因组图谱预测微生物的功能。基因组分析显示，几种肠道微生物与驱动炎症反应途径的细胞因子(如IL-23、IL-17、IL-1、干扰素-γ、肿瘤坏死因子)密切相关。许多微生物与Lewis或Fischer大鼠的炎症独特相关，其中一种与这两种背景都相关。与WT对照组相比，与免疫失调密切相关的几种微生物在HLA-B27TG中并没有明显的丰富。多组网络分析显示，在Lewis和Fischer大鼠中，与重叠的调控失调的免疫/炎症基因密切相关的微生物集群不重叠。普雷沃特氏菌、梭状芽孢杆菌和布鲁氏菌在Lewis大鼠中很重要，而粘液阿克曼氏菌和乳螺科成员在Fischer动物中占主导地位。炎症相关的代谢途径扰动(如丁酸、丙酸、脂多糖和类固醇生物合成)也从这两个背景中被预测。对实验SpA中肠道微生物和宿主免疫反应的组间和网络分析提供了一个前所未有的视角，揭示了与IL-23、IL-17、IL-1、干扰素-γ和肿瘤坏死因子途径密切相关的生物。这些生物体之间的功能相似性可能解释了为什么不同的遗传背景表现出共同的免疫失调模式，可能是通过干扰相似的代谢途径。这些结果突显了将肠道微生物区系分析与宿主免疫反应联系起来的力量，以深入了解非生物微生物在SPA中的作用，而不仅仅是分类特征。
To define inflammation-related host-microbe interactions in experimental spondyloarthritis using novel inter-omic approaches. The relative frequency of gut microbes was determined by 16S rRNA gene sequencing, and gene expression by RNA-seq of host tissue. HLA-B27/human β2-microglobulin transgenic (HLA-B27 TG) and wild type (WT) rats from Dark Agouti, Lewis, and Fischer backgrounds were used. Inter-omic analyses using Cytoscape were employed to identify relevant relationships. PICRUSt was used to predict microbial functions based on known metagenomic profiles. Inter-omic analysis revealed several gut microbes microbes strongly associated with dysregulated cytokines driving inflammatory response pathways (e.g. IL-23, IL-17, IL-1, IFN-γ, TNF). Many microbes were uniquely associated with inflammation in Lewis or Fischer rats, and one was relevant on both backgrounds. Several microbes strongly correlated with immune dysregulation were not differentially abundant in HLA-B27 TG compared to WT controls. Multi-omic network analysis revealed non-overlapping clusters of microbes in Lewis and Fischer rats that were strongly linked to overlapping dysregulated immune/inflammatory genes. Prevotella, Clostridiales, and Blautia were important in Lewis rats, while Akkermansia muciniphila and members of the Lachnospiraceae family dominated in Fischer animals. Inflammation-associated metabolic pathway perturbation (e.g. butanoate, propanoate, LPS, and steroid biosynthesis) was also predicted from both backgrounds. Inter-omic and network anaylsis of gut microbes and the host immune response in experimental SpA provides an unprecedented view of organisms strongly linked to dysregulated IL-23, IL-17, IL-1, IFN-γ, and TNF pathways. Functional similarities between these organisms may explain why different genetic backgrounds exhibit common patterns of immune dysregulation, possibly through perturbation of similar metabolic pathways. These results highlight the power of linking analyses of gut microbiota with the host immune response to gain insights into role of dysbiotic microbes in SpA beyond taxonomic profiling.
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收获状态阻止了HLA-B27转基因大鼠中肠道和关节炎症性疾病的发展。
影响因子：
15.3
作者：
Taurog, Joel D.;Richardson, James A.;Croft, Joanne T.;Simmons, William A.;Zhou, Ming;Fernandez-Sueiro, Jose Luis;Balish, Edward;Hammer, Robert E.
通讯作者：
Hammer, Robert E.
影响因子：
27.4
作者：
Breban, Maxime;Tap, Julien;Sokol, Harry
通讯作者：
Sokol, Harry
DOI：
10.1126/science.aat9076
发表时间：
2018-11-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Litvak Y;Byndloss MX;Bäumler AJ
通讯作者：
Bäumler AJ
影响因子：
4.6
作者：
Nepelska M;de Wouters T;Jacouton E;Béguet-Crespel F;Lapaque N;Doré J;Arulampalam V;Blottière HM
通讯作者：
Blottière HM
DOI：
10.1002/art.40183
发表时间：
2017-10
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Asquith M;Davin S;Stauffer P;Michell C;Janowitz C;Lin P;Ensign-Lewis J;Kinchen JM;Koop DR;Rosenbaum JT
通讯作者：
Rosenbaum JT