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.

描述：阴道微生物区系在维护女性健康方面起着重要的保护作用。破坏阴道内细菌群落与宿主之间存在的互惠关系会导致细菌性阴道病(BV)，在这种情况下，产生乳酸的细菌会被各种严格的厌氧细菌所取代。BV已被证明是不良结局的独立危险因素，包括早产和低出生体重，获得性传播感染和艾滋病毒，以及发展成盆腔炎。全国调查表明，BV在美国女性中的患病率为29.2%，然而，尽管做出了相当大的努力，BV的病因仍不清楚。此外，目前还没有广泛有效的治疗BV的方法，而且复发很常见。在拟议的研究中，我们将检验最重要的假设，即阴道微生物群落动态和活动是BV风险的指标。为此，我们建议进行一项高分辨率的前瞻性研究，每天从200名育龄妇女的两个月经周期收集样本，以捕捉在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来获得所需的数据，以将阴道微生物群落组成和功能、代谢物以及流行病学和行为元数据的变化与BV的发生联系起来，以更好地定义综合征本身，并确定预测BV的模式。这项研究的五个具体目标是：(1)通过表征阴道冲洗停止研究存档的阴道标本的群落组成，评估阴道微生物群落动态与BV风险之间的关系；(2)招募200名妇女参加前瞻性研究，每天收集自收集的阴道拭子和分泌物样本，以及关于BV发生的数据、阴道酸碱度和有关时变习惯和做法的信息；(3)测定阴道微生物群落的基因含量(元基因组)，以评估具有代表性的女性阴道微生物群落在BV自然缓解前、期间和之后的代谢潜力；(4)确定代表健康女性阴道群落类型的社区中表达的基因(元转录组)的特征，以及BV自发缓解前、中和之后的表达基因组；以及(5)应用基于模型的统计聚类和分类方法，将微生物群落的组成和功能与BV的元数据和临床诊断相关联。产生的大量信息将有助于了解阴道微生物群落动态，BV的病原学，并推动BV更好的诊断工具的开发。此外，这些信息将使BV的治疗更加个性化和有效，并最终防止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，但其病因和有效的治疗方法尚不清楚。BV与许多不利的健康后果有关，例如早产低出生体重婴儿和增加感染艾滋病毒的风险。这项研究将有助于提供有关BV病因的有价值的信息，有助于开发改进的预防和治疗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。