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

基本信息

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
项目类别：
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&apos 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

项目摘要

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），其特征是阴道微生物群菌群失调，乳酸菌种类较少，影响近 30% 的美国女性；大多数（55%）无症状（aBV）。目前的指导方针建议仅针对有症状的 BV (sBV) 进行检测和治疗。 BV（aBV 和 aBV 的复合变量有症状的 BV [sBV]）与性传播感染 (STI) 风险增加有关和艾滋病毒感染。尽管研究区分了女性之间发生性传播感染或艾滋病毒的不同风险 aBV 和 sBV 尚未发表，我们小组的初步数据表明 aBV 强烈与性传播感染事件相关以及已发表的针对患有 aBV 的女性进行 BV 抑制治疗的初步研究表明衣原体病例有所减少。迄今为止，对 aBV 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 风险的数据以及对当前可用 BV 功效低下的看法治疗。然而，虽然 BV 治疗具有挑战性，但大约 50% 的 sBV 女性患者服用目前可用的疗法确实可以实现持久治愈。此外，针对 BV 的新颖、更有效的疗法正在开发中地平线：最近一项引人注目的 Lactin V 随机试验，Lactin V 是一种卷曲乳杆菌阴道内活生物治疗药物产品，显示 BV 复发减少13。随着新的、更好的 sBV 治疗方法的出现，至关重要的是确定患有 aBV 的女性是否也应该接受治疗，以预防 STI 或 HIV 等后遗症获得。如果患有 sBV 和 aBV 的女性的阴道微环境是相同的，那么这就是这是一个重要的第一步，表明 aBV 是一个不容忽视的条件，并将激发进一步研究以确定 aBV、STI 和 HIV 风险并推进治疗。在一项针对超过 300 名女性，我们的具体目标是评估患有 aBV 和 sBV 的女性在两大领域是否存在差异 (1) 生物行为因素和 (2) 阴道微环境，包括与 HIV 和 STI 相关的因素获得风险（阴道微生物群、关键代谢物和可溶性炎症介质）。这是一个利用先前资助的研究的现有数据进行二次分析（NIAID R01-AI116799，PI： Brotman），其 16S rRNA 基因扩增子、代谢组学和免疫学特征已经由美国国立卫生研究院阴道菌群纵向研究收集的宫颈阴道灌洗样本产生。通过这项拟议研究获得的信息将为更好地定义 aBV 提供基础数据，并确定未来的研究是否会定义与 aBV 相关的 HIV 和 STI 感染风险，或研究需要将 aBV 治疗作为预防 HIV 和 STI 的一种方法。此重新提交申请位于对旨在探索和发展的计划公告 (PAR-20-291) 的回应 NIAID K 奖获得者的研究资助计划。它将为 PI 提供职业发展通过高度可行且有价值的临床研究项目过渡到研究独立性，重点关注阴道微生物组和女性健康。