The vaginal microenvironment in asymptomatic versus symptomatic bacterial vaginosis

无症状与有症状细菌性阴道病的阴道微环境

• 批准号: 10666011
• 负责人: Susan Anne Tuddenham
• 金额: $ 27.82万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666011
• 关键词: 16S ribosomal RNA sequencing; Affect; Age; American; Anaerobic Bacteria; Antibiotic Therapy; Area; Atopobium vaginae; Automobile Driving; Bacteria; Bacterial Vaginosis; Behavioral; Biogenic Amines; Biological Response Modifier Therapy; Black race; Chlamydia; Clinical Research; Clinical Treatment; Cohort Studies; Data; Data Sources; Databases; Development; Epidemiology; Feminine; Funding; Future; Grant; Guidelines; HIV; HIV risk; HIV-1; Hygiene; IL6 gene; IL8 gene; Immunologic Factors; Immunologics; Inflammation; Inflammation Mediators; Inflammatory; Interferon Type II; Interleukin-1 beta; Irrigation; Isomerism; K-Series Research Career Programs; Lactic acid; Lactobacillus; Lead; Longitudinal Studies; Mediating; Methods; NIH Program Announcements; National Institute of Allergy and Infectious Disease; Output; Pathogenesis; Patients; Perception; Pilot Projects; Predisposition; Publishing; Recommendation; Recurrence; Reproductive Health; Research; Research Project Grants; Risk; Sampling; Sexually Transmitted Diseases; Smoking; Symptoms; Taxonomy; Testing; Uncertainty; United States National Institutes of Health; Vagina; Woman; Women' s Health; adverse outcome; biobehavior; career development; cervicovaginal; condoms; cytokine; design; dysbiosis; effective therapy; epidemiology study; hormonal contraception; improved; infection risk; metabolome; metabolomics; microbiota; negative affect; novel; perceived stress; prevent; programs; rRNA Genes; randomized trial; reproductive; response; secondary analysis; symptom treatment; symptomatology; vaginal microbiome; vaginal microbiota

Bacterial vaginosis (BV), which is characterized by a dysbiotic vaginal microbiota low in Lactobacillus species, affects nearly 30% of U.S. women; the majority (55%) are asymptomatic (aBV). Guidelines currently recommend testing and treatment only for symptomatic BV (sBV). BV (a composite variable with aBV and symptomatic BV [sBV]) has been associated with an increased risk of sexually transmitted infections (STIs) and HIV acquisition. Although studies to distinguish the differential risk of incident STI or HIV between women with aBV and sBV have not been published, preliminary data from our group suggests that aBV is strongly associated with incident STI and a published pilot study of BV suppressive therapy in women with aBV indicated a decrease in chlamydia cases. To date, enthusiasm for research on or clinical treatment of aBV has been limited, primarily by lack of data on aBV risks and perceptions of low efficacy of currently available BV treatments. However, while BV treatment is challenging, approximately 50% of women with sBV taking currently available therapies do achieve lasting cure. Moreover, novel, more effective therapies for BV are on the horizon: a recent high-profile randomized trial of Lactin V, a L. crispatus intravaginal live biotherapeutic product, showed reduced BV recurrence13. As new, better treatments for sBV become available, it is critical to determine whether women with aBV should also be treated, in order to prevent sequelae such as STI or HIV acquisition. If the vaginal microenvironment is shown to be identical in women with sBV and aBV, this will be an important initial step demonstrating that aBV is a condition that should not be ignored, and will galvanize further studies to define aBV, STI and HIV risk, and advance treatment. In a large epidemiologic study of over 300 women, our specific aims are to assess whether women with aBV and sBV differ in two broad areas (1) biobehavioral factors and (2) the vaginal microenvironment, including factors associated with HIV and STI acquisition risk (vaginal microbiota, key metabolites and soluble mediators of inflammation). This is a secondary analysis leveraging existing data from a previously funded study (NIAID R01-AI116799, PI: Brotman) for which 16S rRNA gene amplicon, metabolomic, and immunologic profiles have already been generated from cervicovaginal lavage samples collected in the NIH's Longitudinal Study of Vaginal Flora. Information gained through this proposed study will provide foundational data to better define aBV, and to determine whether future studies to define the risk of HIV and STI acquisition associated with aBV, or studies of aBV treatment as a method to prevent HIV and STIs are needed. This resubmission application is in response to a program announcement (PAR-20-291) which is designed for Exploratory and Developmental Research Grant Program for NIAID K-award Recipients. It will provide career development for the PI to transition to research independence with a highly feasible and valuable clinical research project focused on the vaginal microbiome and women's health.

细菌性阴道病（BV），其特征是乳杆菌中低的生物性阴道微生物群， 影响近30％的美国妇女；大多数（55％）无症状（ABV）。目前的指南 仅建议对有症状的BV（SBV）进行测试和治疗。 BV（具有ABV和ABV的复合变量 有症状的BV [SBV]）与性传播感染的风险增加有关 和艾滋病毒收购。尽管研究以区分妇女之间发生性传播感染或艾滋病毒的差异风险 尚未发布ABV和SBV，我们小组的初步数据表明ABV强烈 与ABV女性的BV抑制疗法有关的事件性传播感染和已发表的BV抑制疗法有关 表明衣原体病例的减少。迄今为止，对ABV的研究或临床治疗的热情已经 受到限制，主要是由于缺乏有关ABV风险的数据和对当前可用BV效力低的看法 治疗。但是，尽管BV治疗具有挑战性，但大约有50％的SBV女性服用 当前可用的疗法确实可以实现持久的治疗方法。此外，新颖，更有效的BV疗法正在开启 地平线：最近的乳酸V，A L. crispatus静脉内生物疗法的备受瞩目的随机试验 产物显示BV复发降低13。随着新的，更好的SBV治疗方法，至关重要 确定是否还应治疗患有ABV的女性，以防止后遗症，例如STI或HIV 获得。如果在SBV和ABV的女性中证明阴道微环境相同 一个重要的初始步骤，证明ABV是不应忽略的条件，并且会镀锌 进一步的研究以定义ABV，性传播感染和艾滋病毒风险并进行预先治疗。在一项大规模的流行病学研究中 300名妇女，我们的具体目的是评估ABV和SBV的妇女在两个广泛领域是否有所不同（1） 生物行为因素和（2）阴道微环境，包括与HIV和STI相关的因素 采集风险（阴道菌群，关键代谢产物和炎症的可溶性介质）。这是一个 二级分析利用先前资助的研究（NIAID R01-AI116799，PI：）利用现有数据： Brotman）16S rRNA基因扩增子，代谢组和免疫学特征已经存在 是由NIH阴道菌群纵向研究中收集的子宫颈灌洗样品产生的。 通过这项拟议的研究获得的信息将提供基础数据，以更好地定义ABV，并 确定未来的研究是否定义了与ABV相关的HIV和STI获取风险或研究 需要将ABV治疗作为预防艾滋病毒和性传播感染的方法。此重新提交申请在 响应计划公告（PAR-20-291），该公告是为探索性和发展而设计的 Niaid K-award接受者的研究赠款计划。它将为PI提供职业发展 过渡到研究独立性，具有高度可行且有价值的临床研究项目，重点是 阴道微生物组和女性健康。