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)，其特征是阴道微生物群中乳杆菌种类较少， 影响到近30%的美国女性；大多数(55%)是无症状(ABV)。目前的指导方针 建议仅对有症状的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)的风险增加有关 和艾滋病病毒的获取。尽管有研究区分女性之间发生性传播感染或艾滋病毒的不同风险 在ABV和SBV尚未发表的情况下，我们小组的初步数据表明，ABV是强有力的 与性传播感染事件和一项已发表的对ABV女性进行BV抑制治疗的先导性研究 显示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 受到限制，主要是因为缺乏关于ABV风险的数据，以及对现有BV疗效较低的看法 治疗。然而，尽管BV治疗具有挑战性，但大约50%患有SBV的女性服用 目前可用的治疗方法确实可以实现持久的治愈。此外，针对BV的新的、更有效的治疗方法正在进行中 地平线：最近一项备受瞩目的LACTIN V随机试验，一种经阴道活体治疗的皱纹夜蛾 产品显示BV复发率降低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的妇女是否也应该接受治疗，以防止STI或HIV等后遗症 收购。如果SBV和ABV女性的阴道微环境被证明是相同的，这将是 重要的第一步表明ABV是一种不应被忽视的情况，并将激励 进一步研究以确定ABV、STI和HIV风险，并推进治疗。在一项大规模的流行病学研究中 300名女性，我们的具体目标是评估患有ABV和SBV的女性是否在两个广泛的领域存在差异(1) 生物行为因素和(2)阴道微环境，包括与艾滋病毒和性传播感染有关的因素 获得性风险(阴道微生物区系、关键代谢物和炎症的可溶性介质)。这是一个 利用先前资助研究的现有数据进行二次分析(NIAID R01-AI116799，PI： 其16S rRNA基因扩增子、代谢组学和免疫学图谱已经被 由美国国立卫生研究院阴道菌群纵向研究中收集的宫颈阴道灌洗液样本产生。 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 确定未来确定与ABV相关的HIV和STI感染风险的研究，还是研究 需要将ABV治疗作为预防艾滋病毒和性传播感染的一种方法。此重新提交的申请在 对专为探索和开发而设计的计划公告(PAR-20-291)的回应 为NIAID K奖获得者提供的研究资助计划。它将为PI提供职业发展，以 通过高度可行和有价值的临床研究项目过渡到研究独立性，重点是 阴道微生物群与女性健康。