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: 8321706
• 负责人: Jacques Ravel
• 金额: $ 25万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-09 至 2012-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8321706
• 关键词: Accounting; Age; Anaerobic Bacteria; Antibiotics; Archives; 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; 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：阴道微生物群在维持女性健康方面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惠关系的破坏可能导致细菌性阴道病 (BV)，在这种情况下，产生乳酸的细菌被多种严格厌氧细菌取代。 BV 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 BV 患病率为 29.2%，然而，尽管付出了巨大努力，BV 的病因仍不清楚。此外，目前尚无广泛有效的治疗 BV 的疗法，并且复发很常见。在拟议的研究中，我们将检验一个总体假设，即阴道微生物群落动态和活动是细菌性阴道病风险的指标。为此，我们建议进行一项高分辨率前瞻性研究，每天从 200 名育龄妇女的两个月经周期中收集样本，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来获取将阴道微生物群落组成和功能、代谢组以及流行病学和行为元数据的变化与细菌性阴道病的发生相关联所需的数据，以更好地定义综合症本身并确定可预测细菌性阴道病的模式。该研究的五个具体目标是：(1) 通过表征阴道冲洗停止研究中存档的阴道标本的群落组成，评估阴道微生物群落的动态与 BV 风险之间的关联，该研究中 39 名女性自行采集了阴道拭子每周两次，持续 16 周； (2) 招募 200 名女性参加一项前瞻性研究，每天收集自行采集的阴道拭子样本和分泌物，以及 BV 发生数据、阴道 pH 值以及随时间变化的习惯和做法的信息； （3）测定阴道微生物群落的基因含量（宏基因组），以评估女性BV自发缓解前、期间和后代表性阴道群落的代谢潜力； (4) 表征代表健康女性阴道群落类型的群落中以及 BV 自发缓解之前、期间和之后的表达基因组（元转录组）； (5) 应用基于模型的统计聚类和分类方法将微生物群落的组成和功能与 BV 的元数据和临床诊断相关联。生成的大量信息将有助于了解阴道微生物群落动态、BV 病因，并推动更好的 BV 诊断工具的开发。此外，这些信息将使细菌性阴道病的治疗更加个性化和有效，并最终预防与这种普遍存在的阴道微生物组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。

项目成果

An improved dual-indexing approach for multiplexed 16S rRNA gene sequencing on the Illumina MiSeq platform.

• DOI: 10.1186/2049-2618-2-6
• 发表时间: 2014-02-24
• 期刊: Microbiome
• 影响因子: 15.5
• 作者: Fadrosh DW;Ma B;Gajer P;Sengamalay N;Ott S;Brotman RM;Ravel J
• 通讯作者: Ravel J

Caring about trees in the forest: incorporating frailty in risk analysis for personalized medicine.

• DOI: 10.2217/pme.11.72
• 发表时间: 2011-11
• 期刊: Personalized medicine
• 影响因子: 2.3
• 作者: Ma ZS;Abdo Z;Forney LJ
• 通讯作者: Forney LJ

Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis.

• DOI: 10.1186/2049-2618-1-29
• 发表时间: 2013-12-02
• 期刊: Microbiome
• 影响因子: 15.5
• 作者: Ravel J;Brotman RM;Gajer P;Ma B;Nandy M;Fadrosh DW;Sakamoto J;Koenig SS;Fu L;Zhou X;Hickey RJ;Schwebke JR;Forney LJ
• 通讯作者: Forney LJ

Nonoptimal Vaginal Microbiota After Azithromycin Treatment for Chlamydia trachomatis Infection.

• DOI: 10.1093/infdis/jiz499
• 发表时间: 2020-02-03
• 期刊: The Journal of infectious diseases
• 作者: Tamarelle J;Ma B;Gajer P;Humphrys MS;Terplan M;Mark KS;Thiébaut ACM;Forney LJ;Brotman RM;Delarocque-Astagneau E;Bavoil PM;Ravel J
• 通讯作者: Ravel J

Investigating the impact of condomless vaginal intercourse and lubricant use on the vaginal metabolome: a pre-post observational study.

调查无套阴道性交和润滑剂使用对阴道代谢组的影响：一项前后观察研究。

• DOI: 10.1136/sextrans-2022-055667
• 发表时间: 2023
• 期刊: Sexually transmitted infections
• 影响因子: 3.6
• 作者: Borgogna,Joanna-LynnC;Grace,SavannahG;Holm,JohannaB;AvilesZuniga,Tadeo;Kadriu,Herlin;He,Xin;McCoski,SarahR;Ravel,Jacques;Brotman,RebeccaM;Yeoman,CarlJ
• 通讯作者: Yeoman,CarlJ