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），其特征在于乳酸杆菌属物种中的微生物群失调， 影响近30%的美国女性;大多数（55%）无症状（aBV）。指南目前 建议仅对症状性BV（sBV）进行检测和治疗。BV（复合变量，aBV和 有症状的BV [sBV]）与性传播感染（STI）的风险增加有关 艾滋病的感染。尽管研究区分了妇女之间性传播感染或艾滋病毒事件的不同风险， aBV和sBV尚未发表，我们小组的初步数据表明，aBV强烈 与STI事件相关，以及一项已发表的aBV女性BV抑制治疗的初步研究 表明衣原体感染病例有所减少。到目前为止，对aBV的研究或临床治疗的热情已经超过了2000年。 主要是由于缺乏aBV风险的数据以及认为目前可用的BV疗效较低， 治疗。然而，虽然BV治疗具有挑战性，但大约50%的sBV女性服用 目前可用的疗法确实实现了持久治愈。此外，新的，更有效的治疗BV的方法正在进行中。 地平线：最近一项备受瞩目的Lactin V随机试验，L.卷曲型阴道内活组织检查 产品，显示BV复发率降低13。随着sBV的新的、更好的治疗方法的出现， 确定aBV妇女是否也应接受治疗，以预防性病或艾滋病毒等后遗症 采集如果sBV和aBV女性的阴道微环境相同， 这是重要的第一步，表明aBV是一种不应忽视的疾病， 进一步研究确定aBV、STI和艾滋病毒风险，并推进治疗。在一项大型流行病学研究中， 300名妇女，我们的具体目标是评估aBV和sBV妇女是否在两个广泛领域存在差异（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 利用先前资助研究（NIAID R 01-AI 116799，PI： Brotman），其16 S rRNA基因扩增子、代谢组学和免疫学特征已经被 从NIH的阴道植物群纵向研究中收集的宫颈阴道灌洗液样本中产生。 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， 确定未来的研究是否定义与aBV相关的HIV和STI获得风险，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。这份重新提交的申请是在 对计划公告（PAR-20-291）的回应，该公告旨在探索和发展 NIAID K奖获得者的研究资助计划。它将为PI提供职业发展， 过渡到研究独立，具有高度可行性和有价值的临床研究项目，重点是 阴道微生物组和女性健康。