Integrated Metagenomic and Metatranscriptomic Characterization of Inflammatory Chronic Rhinosinusitis Endotypes

炎症性慢性鼻窦炎内型的综合宏基因组学和宏转录组学特征

• 批准号: 10078243
• 负责人: Suman Ranjan Das
• 金额: $ 21.25万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10078243
• 关键词: Adaptive Immune System; Affect; Allergic Disease; Asthma; Bacteria; Bacterial Genes; Bioinformatics; Biological Markers; Chronic; Clinical; Clinical Research; Cluster Analysis; Communities; Complement; Complex; Data; Data Analyses; Development; Diagnostic; Direct Costs; Disease; Ecology; Enrollment; Epithelial; Etiology; Evaluation; Functional disorder; Gene Expression; Genes; Genetic Transcription; Genomics; Goals; Grant; Healthcare; Homeostasis; Immune; Immunophenotyping; Inflammation; Inflammatory; Intervention; Lead; Link; Metabolism; Metagenomics; Microbe; Mucositis; Mucous Membrane; Mucous body substance; Pathway interactions; Patients; Phase; Phenotype; Population; Population Control; Prevalence; Quality of life; Research; Research Personnel; Resources; Sampling; Severity of illness; Sinus; Standardization; Structure; Syndrome; Taxonomy; Techniques; Testing; Time; Tissues; Transcript; United States National Institutes of Health; Variant; bacterial community; base; chronic inflammatory disease; chronic rhinosinusitis; clinically relevant; cohort; cytokine; design; genomic data; host microbiome; immune function; insight; interest; metagenomic sequencing; metatranscriptomics; microbial; microbial colonization; microbial community; microbiota; multidisciplinary; multiple omics; nasal microbiome; novel; physical conditioning; prospective; transcriptome; transcriptomics; working group

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.

项目概要 慢性鼻窦炎是一种常见的炎症性疾病，影响着很大一部分美国人， 导致受影响者的生活质量下降，并占用了数十亿美元的医疗资源。这 CRS 的病因仍知之甚少，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。中央 该提案的假设是，临床相关的 CRS 内型由不同的炎症特征定义 与鼻腔微生物群落结构、组成和功能的变化有关。我们将 通过分析大量前瞻性登记的健康对照和 CRS 患者队列来检验这一假设。 具体目标 1 将与我们的研究小组之前使用的方法确定的炎症性 CRS 内型相关联 鼻腔细菌群落分类学变化的层次聚类分析。目标2将 使用综合宏转录组学方法来表征宿主，补充目标 1 的发现 和细菌转录组。这些数据将有助于确定细菌基因的功能相关性和 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 内型的特征是 不仅在细菌群落结构和组成方面存在差异，而且在功能、代谢和功能方面也存在差异。 常驻细菌的转录活性。这项研究的结果将提供对机制的深入了解 CRS 并揭示了以前未确定的鼻窦微生物群与不同类型慢性病之间的关联 鼻窦粘膜炎症。