Molecular Epidemiology of the Vaginal Microbiome

阴道微生物组的分子流行病学

• 批准号: 8042549
• 负责人: REBECCA M. BROTMAN
• 金额: $ 12.88万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-15 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8042549
• 关键词: Anaerobic Bacteria; Antibiotics; Archives; Award; Bacteria; Bacterial Vaginosis; Behavior; Collection; Communities; DNA; Data; Detection; Development; Diagnosis; Diagnostic; Disease remission; Effectiveness; Environment; Epidemiologic Studies; Epidemiology; Etiology; Event; Feminine; Frequencies; Genome; Genomics; Goals; Gold; Gram' s stain; HIV; HIV Infections; Health; Hygiene; Inflammatory; Institutes; Intervention; K-Series Research Career Programs; Lactic acid; Lead; Link; Low Birth Weight Infant; Maryland; Mediating; Menstrual cycle; Metagenomics; Methods; Modeling; Molecular; Molecular Analysis; Molecular Diagnosis; Molecular Epidemiology; Molecular Models; Morbidity - disease rate; Outcome; Parents; Participant; Pattern; Pelvic Inflammatory Disease; Pelvis; Play; Predisposition; Premature Birth; Prevalence; Preventive Medicine; Prospective Studies; Recurrence; Relapse; Relative (related person); Reporting; Reproductive Health; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Rural; Sampling; Science; Sex Behavior; Sexually Transmitted Diseases; Specimen; Spontaneous Remission; Structure; Surveys; Swab; Symptoms; Technology; Testing; Time; Training; Translations; United States; Universities; Vagina; Vaginal Diseases; Vaginal Douching; Woman; Women' s Health; Work; adverse outcome; base; clinical practice; effective therapy; epidemiologic data; improved; medical schools; microbial; microbial community; microbiome; molecular modeling; prevent; professor; rRNA Genes; reproductive; resilience; routine Bacterial stain; tool

DESCRIPTION (provided by applicant): Candidate: Dr. Rebecca Brotman is an Assistant Professor with the Institute for Genome Sciences and the Department of Epidemiology and Preventive Medicine at the University of Maryland School of Medicine. This career development award would allow the candidate to expand her training from classical epidemiology to the analysis and translation of metagenomic data. The candidate will be uniquely trained by the end of the award period to integrate microbiome data in molecular epidemiological studies. Background: Vaginal microbiota play an important protective role in maintaining the health of women. Disruption of the mutualistic relationship that exists between bacterial communities in the vagina and their hosts can lead to bacterial vaginosis (BV), a condition in which lactic acid-producing bacteria are supplanted by a diverse array of strictly anaerobic bacteria. Epidemiologically, BV has been shown to be an independent risk factor for adverse outcomes including preterm birth, acquisition of sexually transmitted infections and HIV, and development of pelvic inflammatory disease. National surveys indicate the prevalence of BV among U.S. women is 29%, and yet, despite considerable effort, the cause of BV remains unknown. Moreover, there are no broadly effective therapies for the treatment of BV and recurrence is common. The overarching goal of this project is to better define BV by linking epidemiologic research on risk factors for BV with genomic research on vaginal microbiota to search for the mechanisms that mediate onset and remission. Methods: We will utilize archived vaginal swabs which were collected twice-weekly by 39 women in a 16-week prospective study (1,107 samples). The specimens capture molecular events that take place before, during, and after the spontaneous remission of BV episodes and over the time course of the menstrual cycle. We will apply cultivation-independent methods based on the analysis of 16S rRNA gene sequences amplified from whole genomic DNA isolated from the vaginal swabs. The specimens provide a unique opportunity to investigate four specific aims: 1) Characterize the changes in structure (species composition and rank abundance) of vaginal microbial communities over time; 2) Develop a molecular model for the diagnosis of BV; 3) Apply model-based statistical approaches to evaluate the relationship between time-varying factors and behaviors with shifts in microbial community composition; and 4) Evaluate the effect of vaginal douching cessation on the vaginal microbiota. Significance: Currently, there is no molecular component to the diagnosis of BV. Use of modern metagenomic technologies in this study will allow us to identify vaginal microbial communities and patterns that are predictive of BV. The proposed studies will facilitate our understanding of vaginal microbiota, drive the development of diagnostic tools for BV and may lead to improved methods for preventing and treating BV. Bacterial vaginosis (BV) is the most common vaginal disease in women, and yet its cause and effective treatment remain unknown. BV is associated with many adverse health outcomes, such as preterm delivery of low birth weight babies and increased risk for infection by HIV. This research will contribute valuable information on the causes of BV, help develop improved methods for diagnosing, preventing and treating BV, and may help reduce major reproductive health problems associated with BV.

描述（由申请人提供）：候选人：丽贝卡·布罗特曼（Rebecca Brotman）博士是马里兰大学医学院的基因组科学研究所和流行病学和预防医学系的助理教授。该职业发展奖将使候选人能够将她的培训从经典流行病学扩展到元基因组数据的分析和翻译。候选人将在奖励期结束时进行独特的培训，以在分子流行病学研究中整合微生物组数据。 背景：阴道菌群在维持女性健康方面起着重要的保护作用。阴道中细菌群落及其宿主之间存在的相互关系的破坏会导致细菌性阴道病（BV），在这种情况下，产生乳酸的细菌被多种严格的厌氧细菌所取代。从流行病学上讲，BV已被证明是不良后果的独立危险因素，包括早产，获得性传播感染和HIV以及骨盆炎性疾病的发展。全国调查表明，美国妇女中BV的流行率为29％，但是，尽管付出了巨大的努力，但BV的原因仍然未知。此外，没有广泛有效的BV治疗疗法，并且复发是常见的。该项目的总体目标是通过将BV风险因素的流行病学研究与阴道微生物群的基因组研究联系起来，以更好地定义BV，以搜索介导和缓解的机制。 方法：我们将利用39名妇女在16周的前瞻性研究（1,107个样本）中每周两次收集的存档阴道拭子。标本捕获了BV发作自发缓解之前，期间和之后发生的分子事件以及月经周期的时间过程。我们将基于对从阴道拭子分离的整个基因组DNA扩增的16S rRNA基因序列的分析采用培养非依赖性方法。这些标本提供了一个独特的机会来研究四个特定目的：1）随着时间的流逝，阴道微生物群落的结构变化（物种成分和等级丰度）的变化； 2）开发用于诊断BV的分子模型； 3）应用基于模型的统计方法来评估随时间变化的因素和行为之间的关系，并随着微生物社区组成的转变； 4）评估阴道浸停止对阴道菌群的影响。 意义：目前，BV的诊断没有分子成分。在这项研究中，使用现代核能技术将使我们能够鉴定出可预测BV的阴道微生物群落和模式。拟议的研究将促进我们对阴道菌群的理解，推动BV的诊断工具的开发，并可能导致改进的预防和治疗BV的方法。细菌性阴道病（BV）是女性最常见的阴道疾病，但其原因和有效治疗尚不清楚。 BV与许多不良健康结果有关，例如早产减肥婴儿和艾滋病毒感染的风险增加。这项研究将贡献有关BV原因的宝贵信息，有助于开发改进的诊断，预防和治疗BV的方法，并可能有助于减少与BV相关的主要生殖健康问题。