Integrated Metagenomic and Metatranscriptomic Characterization of Inflammatory Chronic Rhinosinusitis Endotypes

项目摘要 慢性鼻窦炎是一种常见的炎症性疾病，影响到很大一部分美国人口， 导致受影响者的生活质量不佳，并利用数十亿美元的卫生保健资源。这个 CRS的病因仍然知之甚少，但目前的证据表明，先天和 适应性免疫系统，导致持续的粘膜炎症和微生物定植。中环 这一建议的假设是，临床上相关的CRS内型由不同的炎症信号定义 与鼻腔微生物群落结构、组成和功能的变化有关。我们会 通过分析一大批预期登记的健康对照和CRS患者来验证这一假设。 特定目标1将与我们研究小组先前确定的炎性CRS内型相关 鼻腔细菌群落分类变化的系统聚类法分析。目标2将 使用整合的后转录剪辑学方法补充来自AIM 1的发现，以表征宿主 和细菌转录组。这些数据将有助于确定细菌基因和 转录本存在于CRS中，并识别内型之间的潜在差异，同时还评估相关 宿主转录组的变化。我们假设炎症性CRS内型将通过 不仅在细菌群落结构和组成上，而且在功能、新陈代谢和 驻留细菌的转录活性。这项研究的发现将为深入了解 并揭示了鼻窦微生物区系与不同类型的慢性阻塞性肺疾病之间的联系。 鼻腔粘膜炎症。

Project Summary Chronic rhinosinusitis is a common inflammatory disease that affects a large portion of the U.S. population, resulting in poor quality of life for those affected and utilizing billions of dollars of health care resources. The etiology of CRS remains poorly understood but current evidence points to a dysregulation of the innate and adaptive immune system that results in persistent mucosal inflammation and microbial colonization. The central hypothesis of this proposal is that clinically relevant CRS endotypes defined by distinct inflammatory signatures are associated with changes to sinonasal microbiome community structure, composition, and function. We will test this hypothesis by analyzing a large prospectively enrolled cohort of healthy control and CRS patients. Specific Aim 1 will correlate inflammatory CRS endotypes previously identified by our research group using hierarchical cluster analysis with taxonomic changes to the sinonasal bacterial community. Aim 2 will complement findings from Aim 1 using an integrated metatranscriptomic approach to characterize both the host and bacterial transcriptome. This data will help determine the functional relevance of bacterial genes and transcripts present in CRS, and identify potential differences between endotypes, while also assessing related changes to the host transcriptome. We hypothesize that inflammatory CRS endotypes will be distinguished by variations not only in bacterial community structure and composition, but also in the function, metabolism, and transcriptional activity of resident bacteria. Findings from this study will provide insight into the mechanism of CRS and reveal previously unidentified associations between the sinus microbiota and different types of chronic mucosal inflammation in the sinonasal cavity.