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：Rebecca Brotman博士是马里兰州医学院基因组科学研究所和流行病学与预防医学系的助理教授。这个职业发展奖将允许候选人将她的培训从经典流行病学扩展到宏基因组数据的分析和翻译。候选人将在奖励期结束前接受独特的培训，以将微生物组数据整合到分子流行病学研究中。 背景：阴道微生物群在维持女性健康方面起着重要的保护作用。阴道中细菌群落与其宿主之间存在的互惠关系的破坏可能导致细菌性阴道病（BV），这是一种产乳酸细菌被各种严格厌氧细菌取代的情况。在流行病学上，BV已被证明是不良结局的独立风险因素，包括早产、性传播感染和HIV的获得以及盆腔炎的发展。全国性调查表明，美国妇女中BV的患病率为29%，然而，尽管付出了相当大的努力，BV的原因仍然未知。此外，没有广泛有效的治疗BV的疗法，复发是常见的。该项目的总体目标是通过将BV危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，从而寻找介导发病和缓解的机制。 方法：我们将使用存档的阴道拭子，这些拭子是在一项为期16周的前瞻性研究（1,107份样本）中由39名女性每周采集两次。这些标本捕获了BV发作自发缓解之前、期间和之后以及月经周期时间过程中发生的分子事件。我们将应用基于从阴道拭子分离的全基因组DNA扩增的16 S rRNA基因序列分析的非培养依赖性方法。这些标本提供了一个独特的机会来研究四个特定的目标：1）描述结构的变化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与微生物群落组成变化之间的关系;和4）评估阴道冲洗停止对阴道微生物群的影响。 意义：目前，BV的诊断还没有分子组成部分。在这项研究中使用现代宏基因组技术将使我们能够识别阴道微生物群落和预测BV的模式。拟议的研究将促进我们对阴道微生物群的理解，推动BV诊断工具的开发，并可能导致预防和治疗BV的方法的改进。细菌性阴道病（BV）是女性最常见的阴道疾病，但其原因和有效的治疗方法仍然未知。BV与许多不利的健康结果有关，例如早产低出生体重婴儿和增加感染艾滋病毒的风险。这项研究将提供关于BV病因的有价值的信息，有助于开发诊断、预防和治疗BV的改进方法，并可能有助于减少与BV相关的主要生殖健康问题。