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: 9896586
• 负责人: Suman Ranjan Das
• 金额: $ 25.5万
• 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/9896586
• 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; Epithelium; 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.

项目摘要 慢性鼻塞炎是一种常见的炎症性疾病，影响美国大部分人群， 对于受影响和利用数十亿美元的医疗资源的人来说，导致生活质量差。这 CRS的病因仍然知之甚少，但目前的证据表明先天性的失调和 自适应免疫系统，导致持续性粘膜炎症和微生物定植。中央 该提议的假设是，由不同的炎症特征定义的临床相关CRS内型 与Sinonasal微生物组社区结构，组成和功能的变化有关。我们将 通过分析大量前瞻性招募的健康对照组和CRS患者的队列来检验这一假设。 特定的目标1将使用我们的研究小组先前确定的炎症性CRS内型使用 分类学分析，分类学变化对鼻窦细菌群落。 AIM 2意志 使用集成的元文字方法来补充AIM 1的发现，以表征两个主机 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 CRS中存在的成绩单，并确定内型之间的潜在差异，同时还评估相关 更改主机转录组。我们假设炎症性CRS内型将由 不仅在细菌群落结构和组成中，而且在功能，代谢和 居民细菌的转录活性。这项研究的发现将洞悉 CRS并揭示了鼻窦微生物群和不同类型的慢性的先前未鉴定的关联 鼻窦腔中的粘膜炎症。