The Microbial Ecology of Bacterial Vaginosis: A Fine Scale Resolution Metagenomic

细菌性阴道病的微生物生态学：精细分辨率宏基因组学

• 批准号: 8146536
• 负责人: Jacques Ravel
• 金额: $ 61.73万
• 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: 2010-09-27 至 2012-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8146536
• 关键词: Accounting; Age; Anaerobic Bacteria; Antibiotics; Archives; Arts; Bacteria; Bacterial Vaginosis; Behavior; Behavioral; Classification; Clinical; Communities; Data; Data Analyses; Development; Diagnostic; Disease; Ecology; Ecosystem; Effectiveness; Endometritis; Enrollment; Environment; Epidemiology; Etiology; Event; Frequencies; Gene Expression; Genes; Genomics; HIV; HIV Infections; Habits; Health; Immunologics; Incidence; Individual; Intervention; Lactic acid; Lead; Low Birth Weight Infant; Menstrual cycle; Metabolic; Metadata; Metagenomics; Methods; Modeling; Molecular; Outcome; Pattern; Pelvic Inflammatory Disease; Phase; Pilot Projects; Play; Population Dynamics; Postpartum Period; Premature Birth; Prevalence; Prospective Studies; Relapse; Reproductive Health; Research; Resolution; Risk; Risk Factors; Role; Rural; Sampling; Sexually Transmitted Diseases; Specimen; Spontaneous Remission; Statistical Models; Structure; Surveys; Swab; Symptoms; Syndrome; Technology; Testing; Time; United States; Vagina; Vaginal Discharge; Vaginal Diseases; Vaginal Douching; Woman; Women' s Health; adverse outcome; base; clinical Diagnosis; disease characteristic; effective therapy; improved; metabolomics; microbial; microbial community; microbiome; prevent; prognostic; public health relevance; rRNA Genes; reproductive; resilience; tool

DESCRIPTION: The 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. BV has been shown to be an independent risk factor for adverse outcomes including preterm delivery and low infant birth weight, 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 29.2%, and yet, despite considerable effort, the etiology of BV remains unknown. Moreover, there are no broadly effective therapies for the treatment of BV, and reoccurrence is common. In the proposed research we will test the overarching hypothesis that vaginal microbial community dynamics and activities are indicators of risk to BV. To do this, we propose to conduct a high resolution prospective study in which samples collected daily from 200 reproductive-age women over two menstrual cycles are used to capture molecular events that take place before, during, and after the spontaneous remission of BV episodes. We will use modern genomic technologies to obtain the data needed to correlate shifts in vaginal microbial community composition and function, metabolomes, and epidemiological and behavioral metadata with the occurrence of BV to better define the syndrome itself and identify patterns that are predictive of BV. The five specific aims of the research are: (1) Evaluate the association between the dynamics of vaginal microbial communities and risk to BV by characterizing the community composition of vaginal specimens archived from a vaginal douching cessation study in which 39 women self-collected vaginal swabs twice-weekly for 16 weeks; (2) Enroll 200 women in a prospective study in which self-collected vaginal swab samples and secretions are collected daily along with data on the occurrence of BV, vaginal pH, and information on time varying habits and practices; (3) Determine the gene content (metagenome) of vaginal microbial communities to assess the metabolic potential of representative vaginal communities in women before, during, and after the spontaneous remission of BV; (4) Characterize suites of expressed genes (metatranscriptome) in communities representative of vaginal community types in healthy women, as well as before, during, and after the spontaneous remission of BV; and (5) Apply model-based statistical clustering and classification approaches to associate the microbial community composition and function, with metadata and clinical diagnoses of BV. The large body of information generated will facilitate understanding of vaginal microbial community dynamics, the etiology of BV, and drive the development of better diagnostic tools for BV. Furthermore, the information will enable a more personalized and effective treatment of BV and ultimately, prevent adverse sequelae associated with this highly prevalent disruption of the vaginal microbiome. PUBLIC HEALTH RELEVANCE: 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 preventing and treating BV, and may help reduce major reproductive health problems associated with BV.

阴道微生物群在维持女性健康方面起着重要的保护作用。阴道内细菌群落与其宿主之间的互惠关系被破坏可导致细菌性阴道病（BV），在这种情况下，产生乳酸的细菌被各种各样的严格厌氧细菌所取代。细菌性阴道炎已被证明是不良后果的独立危险因素，包括早产和婴儿出生体重过低，获得性传播感染和艾滋病毒，以及盆腔炎的发展。全国调查显示，美国女性的细菌性阴道炎患病率为29.2%，然而，尽管付出了相当大的努力，细菌性阴道炎的病因仍不清楚。此外，目前还没有广泛有效的治疗细菌性阴道炎的方法，而且复发是很常见的。在拟议的研究中，我们将测试阴道微生物群落动态和活动是BV风险指标的总体假设。为此，我们建议进行一项高分辨率的前瞻性研究，在该研究中，每天从200名育龄妇女中收集两个月经周期的样本，用于捕获BV发作自发缓解之前，期间和之后发生的分子事件。我们将使用现代基因组技术获取所需的数据，将阴道微生物群落组成和功能、代谢组、流行病学和行为元数据的变化与细菌性阴道炎的发生联系起来，以更好地定义该综合征本身，并确定预测细菌性阴道炎的模式。该研究的五个具体目的是：(1)通过对39名妇女在16周内每周两次自行收集阴道拭子的阴道灌洗研究中保存的阴道标本的群落组成特征，评估阴道微生物群落动态与细菌性阴道炎风险之间的关系；(2)招募200名女性进行前瞻性研究，每天收集自己的阴道拭子样本和分泌物，同时收集BV的发生情况、阴道pH值以及随时间变化的生活习惯和实践信息；(3)测定阴道微生物群落基因含量（宏基因组），评估女性BV自发缓解前、缓解中、缓解后代表性阴道群落的代谢潜力；(4)在健康女性阴道群落类型的代表群体中，以及在BV自发缓解之前、期间和之后，表征表达的基因组（亚转录组）；(5)应用基于模型的统计聚类和分类方法，将微生物群落组成和功能与细菌性肠胃炎的元数据和临床诊断联系起来。所产生的大量信息将有助于了解阴道微生物群落动态，细菌性阴道炎的病因，并推动开发更好的细菌性阴道炎诊断工具。此外，这些信息将使BV的治疗更加个性化和有效，并最终预防与这种高度普遍的阴道微生物群破坏相关的不良后遗症。公共卫生相关性：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仍不清楚。细菌性阴道炎与许多不利的健康结果有关，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细菌性阴道炎病因的宝贵信息，有助于开发预防和治疗细菌性阴道炎的改进方法，并可能有助于减少与细菌性阴道炎有关的主要生殖健康问题。