Microbial ecology in the Chronic Rhinosinusitis Microbiome

慢性鼻窦炎微生物群中的微生物生态学

• 批准号: 7982532
• 负责人: Jeffrey T. Foster
• 金额: $ 48.49万
• 依托单位: NORTHERN ARIZONA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7982532
• 关键词: Adrenal Cortex Hormones; Affect; Aftercare; American; Analysis of Variance; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Bacteria; Biological Assay; Biomedical Research; Categories; Clinical; Collaborations; Communities; Consensus; Cross-Sectional Studies; Data; Development; Diagnosis; Diagnostic; Disease; Ecology; Effectiveness; Environment; Evaluation; Expenditure; Exposure to; Goals; Health; Health Care Costs; Healthcare; Hospitals; Human; Human Microbiome; Immune response; Infection; Inflammation; Inflammatory; Inflammatory Response; Institution; Interest Group; Knowledge; Lead; Literature; Maxillary Sinus; Methodology; Methods; Metric; Molecular; Mucositis; Multivariate Analysis; Nasal Polyps; Nose; Office Visits; Oral; Pathogenesis; Patients; Prevalence; Qualifying; Research; Research Institute; Role; Sampling; Sinus; Steroid therapy; Students; Swab; Symptoms; Testing; Time; Translational Research; United States; base; chronic rhinosinusitis; cytokine; immune function; improved; microbial; microbiome; pathogen; polyposis; public health relevance; rRNA Genes; respiratory; tool; trend

DESCRIPTION (provided by applicant): Chronic rhinosinusitis (CRS) is estimated to affect 31 million American and lead to 12.5 million physician office visits and $4.3 billion in healthcare costs each year. Yet, CRS management and diagnosis remain consensus-based. Currently, patients are diagnosed with CRS by a combination of symptoms lasting for e 12 weeks, confirmed with clinical findings. First-line CRS therapy consists of a combination of empiric systemic antibiotic therapy with topical or oral steroid therapy, which has been associated with increased antibiotic-resistance in patients with CRS. To improve effectiveness of CRS management and to minimize the unnecessary use of broad-spectrum antibiotics, elucidation of the contribution of host inflammatory response and microbial pathogens in CRS pathogenesis is essential. The long-term goal of our research is to determine the role of sinus microbiota in CRS pathogenesis. The central hypothesis of this proposal is that sinus inflammation-likely resulting from dysregulated host mucosal immune function-precedes and drives the change in the sinus microbiota. In our preliminary assessment of the sinus bacterial microbiota in control and CRS subjects with and without nasal polyposis (CRSwNP and CRSsNP, respectively) using 16S rRNA gene-based pyrosequencing, we detected a greater than expected level of bacterial diversity in both groups and unique trends in microbiota in each group of interest. We also found two potential microbiota core types in the paranasal sinus: a diverse versus a single- bacteria dominated microbiota. The prevalence of single-bacteria dominated microbiota was highest in the non-treated CRSwNP patients, followed by post-corticosteroids CRSwNP patients, CRSsNP, and controls. This led us to hypothesize that we will be able to demonstrate unique, albeit potentially overlapping, microbiota types in each patient group (SA-1). We further hypothesized that by comparing prospectively collected pre- and post-treatment samples from CRSwNP patients, we will be able to detect a shift from CRSwNP microbiota towards non-CRS microbiota (SA-2). Our proposed research will achieve one of the primary objectives of the Human Microbiome Project, which seeks to elucidate the association between microbiota and human health and disease. The collaboration between an academic institution (NAU), a non-profit translational research institute (TGen), and an academic clinical department (Johns Hopkins) is uniquely qualified to perform the proposed research and to provide NAU students with exposure to meritorious biomedical research, as well as to enhance the research environment at NAU. PUBLIC HEALTH RELEVANCE: Chronic rhinosinusitis (CRS) is a common and costly inflammatory disease that is usually treated with oral antibiotics, which has been associated with an increase in antibiotic-resistance. Yet, we do not fully understand the role of bacteria in the development of CRS. In this study, we will use molecular methods to compare the bacterial community in the healthy and diseased sinus and study the impact of controlling inflammation on the sinus bacterial community.

描述（由申请人提供）：据估计，慢性鼻塞炎（CRS）会影响3100万美国人，并导致1250万医师办公室就诊和每年43亿美元的医疗保健费用。但是，CRS管理和诊断仍然基于共识。目前，通过临床发现证实，通过持续E 12周的症状结合持续的症状结合诊断患者CRS。一线CRS治疗包括经验性全身抗生素治疗与局部或口服类固醇治疗的组合，这与CRS患者的抗生素耐药性增加有关。为了提高CRS管理的有效性，并最大程度地减少了不必要的广谱抗生素使用，阐明了CRS发病机理中宿主炎症反应和微生物病原体的贡献是必不可少的。 我们研究的长期目标是确定鼻窦微生物群在CRS发病机理中的作用。该提案的中心假设是，鼻窦炎症是由失调的宿主粘膜免疫功能 - 肌肉功能 - 促进鼻窦炎症，并驱动了鼻窦微生物群的变化。在我们对对照组和具有鼻多息护物的CRS受试者（分别为CRSWNP和CRSSSNP）中对对照组和CRS受试者的鼻窦细菌菌群的初步评估（分别为CRSWNP和CRSSNP），使用16S rRNA基因基因测序，我们在每个组中的小组中的细菌多样性和独特的趋势中都检测到比预期的细菌多样性水平更大。我们还发现了旁那鼻窦中两种潜在的微生物核心类型：多样性与单细菌主导的微生物群。在未治疗的CRSWNP患者中，单细菌主导的微生物群的患病率最高，其次是cRSSWNP患者，CRSSSNP和对照组。这导致我们假设我们能够证明每个患者组（SA-1）中有可能重叠的微生物群，尽管可能是重叠的。我们进一步假设，通过比较了CRSWNP患者的前瞻性收集的治疗前和治疗后样品，我们将能够检测到从CRSWNP微生物群向非CRS Microbobiota（SA-2）的转变。 我们提出的研究将实现人类微生物组项目的主要目标之一，该项目旨在阐明微生物群与人类健康和疾病之间的关联。学术机构（NAU），非营利转化研究所（TGEN）与学术临床部（Johns Hopkins）之间的合作具有独特的资格，有资格进行拟议的研究，并为NAU的NAU研究环境增强了NAU研究环境。 公共卫生相关性：慢性鼻塞炎（CRS）是一种常见且昂贵的炎症性疾病，通常接受口服抗生素治疗，这与抗生素耐药性的增加有关。但是，我们不完全了解细菌在CRS发展中的作用。在这项研究中，我们将使用分子方法比较健康和患病的窦中细菌群落，并研究控制炎症对窦细菌群落的影响。