Organ-level protein networks as a reference for the host effects of the microbiome
Organ-level protein networks as a reference for the host effects of the microbiome
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DOI：
10.1101/gr.256875.119
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发表时间：
2020-02-01
期刊：
影响因子：
7
通讯作者：
Gonzalez, David J.
中科院分区：
文献类型：
--
作者：
Mills, Robert H.;Wozniak, Jacob M.;Gonzalez, David J.
微生物组与健康之间的联系正在广泛的疾病中迅速出现。然而，对不同微生物群落如何影响宿主的详细机制了解往往是缺乏的。研究人员用来了解这些影响的一种方法是无菌（GF）小鼠模型。在这些模式生物的器官系统中发现的差异可能突出了微生物群失调在整个宿主中的普遍机制。在这里，我们对常规饲养和GF小鼠的大脑、脾脏、心脏、小肠和结肠进行了多重定量蛋白质组学研究，鉴定了超过7000种蛋白质与定植状态的关联。高排名的关联被构建成蛋白质-蛋白质相互作用网络，并可视化到交互式3D小鼠模型上，供用户引导探索。这些结果作为微生物组研究人员希望确定微生物组定植在特定器官上的宿主效应的资源。我们的结果包括验证先前报道的对异种代谢、先天免疫系统和谷氨酸相关蛋白的影响，同时提供生物体范围的背景。我们强调了线粒体蛋白在生物体范围内的差异，包括在常规小鼠的所有分析器官中NNT的持续增加，NNT是一种线粒体蛋白，在影响NADH和NADPH水平中起重要作用。我们的网络还揭示了进一步探索的新关联，包括脾脏中的蛋白酶反应，心脏中的高密度脂蛋白和大脑中的谷氨酸能信号。总的来说，我们的研究通过详细的表格和可视化的微生物定植对几个器官系统的蛋白质水平影响，为微生物组研究人员提供了资源。
Connections between the microbiome and health are rapidly emerging in a wide range of diseases. However, a detailed mechanistic understanding of how different microbial communities are influencing their hosts is often lacking. One method researchers have used to understand these effects are germ-free (GF) mouse models. Differences found within the organ systems of these model organisms may highlight generalizable mechanisms that microbiome dysbioses have throughout the host. Here, we applied multiplexed, quantitative proteomics on the brains, spleens, hearts, small intestines, and colons of conventionally raised and GF mice, identifying associations to colonization state in over 7000 proteins. Highly ranked associations were constructed into protein-protein interaction networks and visualized onto an interactive 3D mouse model for user-guided exploration. These results act as a resource for microbiome researchers hoping to identify host effects of microbiome colonization on a given organ of interest. Our results include validation of previously reported effects in xenobiotic metabolism, the innate immune system, and glutamate-associated proteins while simultaneously providing organism-wide context. We highlight organism-wide differences in mitochondrial proteins including consistent increases in NNT, a mitochondrial protein with essential roles in influencing levels of NADH and NADPH, in all analyzed organs of conventional mice. Our networks also reveal new associations for further exploration, including protease responses in the spleen, high-density lipoproteins in the heart, and glutamatergic signaling in the brain. In total, our study provides a resource for microbiome researchers through detailed tables and visualization of the protein-level effects of microbial colonization on several organ systems.