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 博士是马里兰大学医学院基因组科学研究所以及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其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时接受独特的培训，将微生物组数据整合到分子流行病学研究中。 背景：阴道微生物群对维持女性健康发挥着重要的保护作用。阴道细菌群落与其宿主之间存在的互利关系的破坏可能导致细菌性阴道病 (BV)，在这种情况下，产乳酸菌被多种严格厌氧菌取代。从流行病学角度来看，细菌性阴道炎已被证明是导致早产、性传播感染和艾滋病毒以及盆腔炎等不良后果的独立危险因素。全国调查显示，美国女性 BV 患病率为 29%，然而，尽管付出了巨大努力，BV 的病因仍不清楚。此外，尚无广泛有效的治疗 BV 的疗法，并且复发很常见。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，以寻找介导发病和缓解的机制，从而更好地定义 BV。 方法：我们将利用存档的阴道拭子，这些拭子是由 39 名女性在为期 16 周的前瞻性研究中每周收集两次（1,107 个样本）。这些标本捕捉了 BV 发作自发缓解之前、期间和之后以及月经周期期间发生的分子事件。我们将应用基于对从阴道拭子中分离的全基因组 DNA 扩增的 16S rRNA 基因序列进行分析的独立于培养的方法。这些标本提供了一个独特的机会来研究四个具体目标：1）表征阴道微生物群落结构（物种组成和等级丰度）随时间的变化； 2）开发诊断BV的分子模型； 3）应用基于模型的统计方法来评估随微生物群落组成变化的时变因素和行为之间的关系； 4) 评估停止阴道冲洗对阴道微生物群的影响。 意义：目前，尚无诊断 BV 的分子成分。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微生物群的了解，推动 BV 诊断工具的开发，并可能改进预防和治疗 BV 的方法。细菌性阴道病（BV）是女性最常见的阴道疾病，但其病因和有效治疗方法仍不清楚。 BV 与许多不良健康结果相关，例如低出生体重婴儿的早产和感染艾滋病毒的风险增加。这项研究将提供有关 BV 病因的宝贵信息，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。