The Role of the Vaginal Microbiota in Urgency Urinary Incontinence in Older Women

阴道微生物群在老年女性急迫性尿失禁中的作用

基本信息

批准号：
10028090
负责人：
A. Lenore Ackerman
金额：
$ 16.7万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2020-09-16
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10028090
关键词：
Aerococcus Affect Age Aging Anatomy Anti-Bacterial Agents Anti-Inflammatory Agents Antibiotics Atopobium vaginae Atrophic Bacteria Bladder Bladder Dysfunction Cells Characteristics Chronic Communities Cross-Sectional Studies Cytology Data Decision Making Detection Diabetes Mellitus Disease Dose Enrollment Epidemiologic Factors Epithelial Epithelium Estradiol Estrogen Therapy Estrogens Etiology Exhibits Female Functional disorder Future Genitourinary System Infection Genitourinary system Health Health Care Costs Histologic Host resistance Impairment Individual Inflammation Intervention Intervention Trial Intravaginal Administration Lactobacillus Measures Menopausal Status Menopause Mental Depression Methods Microbe Outcome Overactive Bladder Participant Patient Outcomes Assessments Patients Pattern Physical activity Physiological Physiology Pilot Projects Postmenopause Premenopause Prevalence Prognostic Marker Public Health Quality of life Recording of previous events Resistance Resolution Role Severities Source Sterility Structure Supplementation Symptoms Testing Underserved Population Urinary Incontinence Urinary tract Urinary tract infection Urine Vagina Woman bacterial community disabling symptom falls improved incontinence symptom indexing microbial microbial community microbiome microbiome alteration microbiota micturition urgency next generation sequencing novel novel strategies older women resistance factors restoration sex transmission process urinary urogenital tract urologic vaginal infection vaginal lactobacilli vaginal microbiome vaginal microbiota

项目摘要

PROJECT SUMMARY Urgency Urinary Incontinence (UUI), the hallmark of overactive bladder (OAB), is a prevalent, chronic condition disproportionately affecting postmenopausal women. The debilitating symptoms substantially degrade physical activity and quality of life, yet despite the heavy burden on public health, little is understood of the pathophysiology of UUI. Multiple epidemiologic factors implicate a microbial influence in this disease. New detection methods have revealed microbial communities within the urinary tract, once thought to be sterile, and implicated changes in these communities in UUI. The role of these alterations in the urine is unclear, but in the vagina, loss of protective Lactobacilli after menopause leads to increased vaginal pH, increased local inflammation, and impaired resistance to both vaginal and urinary infections. Early data suggest free exchange of urinary and vaginal bacteria; thus, vaginal microbiota may promote UUI via transmission of this loss of protective Lactobacilli in the urine, promoting similar changes in bladder function as seen in the vagina. In postmenopausal women, vaginal estrogen supplementation can improve UUI symptoms, but the mechanism of this improvement is unknown. As vaginal estrogen can also alter vaginal bacteria, increasing the abundance of Lactobacilli, we hypothesize that vaginal estrogen will impact urinary microbiota in a similar way to ameliorate UUI symptoms. To examine the relation between vaginal and urinary microbiota and UUI symptoms, we will conduct a pre-post pilot study in postmenopausal women with UUI, who are <10 years from menopause and estrogen-naïve. We will use next-generation sequencing to define the baseline urinary and vaginal microbiota, validated OAB-specific patient-reported measures to assess the severity and impact of UUI symptoms, and vaginal cytologic indices to define vaginal epithelial quality. After a 3-month trial of standard-dose vaginal estrogen, these measures will be repeated. This proposal seeks to describe baseline vaginal features of postmenopausal women with UUI by characterizing vaginal microbiota of postmenopausal women with UUI and its concordance with urinary microbiota, and assessing vaginal epithelial quality at baseline in women with UUI. After the intervention, we will explore the effect of vaginal estrogen administration on: a) vaginal and urinary microbiota and b) vaginal quality indices in postmenopausal women with UUI and their relation to improvements in UUI symptom severity, allowing an exploration of the baseline participant characteristics positively associated with improvements in vaginal and urinary microbiota as well as the amelioration of UUI symptoms. We expect this will confirm the association of a loss of protective vaginal microbial communities and decreased vaginal epithelial quality with worsening UUI symptoms and provide evidence that local estrogen supplementation promotes symptomatic resolution by modifying vaginal microbiota and improving epithelial quality. Such findings would reveal novel approaches to treatment aimed at manipulation of the vaginal microbiome, which will provide the basis for larger, interventional trials for this underserved population.

项目摘要紧急尿失禁（UUI），过度活跃的膀胱（OAB）的标志，是一种普遍的慢性病对绝经后妇女的影响不成比例。令人衰弱的症状大大降解了物理活动和生活质量，尽管对公共卫生有沉重的伯恩，但对 UUI的病理生理学。多个流行病学因素暗示对该疾病的微生物影响。新的检测方法揭示了尿路内的微生物群落，一旦被认为是无菌的，并且在UUI中实施了这些社区的变化。这些改变在尿液中的作用尚不清楚，但在阴道，更年期后受保护的乳酸杆菌的丧失导致阴道pH增加，局部增加炎症，以及对阴道和泌尿感染的抗药性受损。早期数据表明免费交换尿和阴道细菌；因此，阴道菌群可以通过传播这种损失来促进UUI 尿液中的保护性乳杆菌，促进了阴道中膀胱功能的类似变化。绝经后女性，补充阴道雌激素可以改善UUI症状，但是这种改进是未知的。由于阴道雌激素也可以改变阴道细菌，从而增加乳酸杆菌，我们假设阴道雌激素会以相似的方式影响尿菌群 UUI符号。为了检查阴道和尿菌群与UUI符号之间的关系，我们将对UUI的绝经后妇女进行了前期试点研究，从年期和我们将使用下一代测序来定义基线尿和阴道菌群，经过验证的OAB特定患者报告的措施，以评估UUI符号的严重程度和影响，并阴道细胞学指数定义阴道上皮质量。经过3个月的标准剂量阴道试验雌激素，这些措施将被重复。该建议旨在描述阴道基线的阴道特征绝经后妇女患有UUI的妇女，表征了UUI和UUI和它与尿液菌群的一致性，并评估UUI女性基线时阴道上皮质量。干预后，我们将探讨阴道雌激素给药的影响：a）阴道和尿 Microbiota和b）绝经后妇女的阴道质量指数及其与改善的关系在UUI症状严重程度中，允许探索基线参与特征正相关随着阴道和尿菌群的改善以及UUI符号的改善。我们期望这将确认丧失受保护的阴道微生物群落并改善阴道的关联上皮质量和后悔的UUI症状，并提供了补充局部雌激素的证据通过修饰阴道菌群并提高上皮质量来促进症状分辨率。这样的发现将揭示针对操纵阴道微生物组的治疗方法的新方法，这将提供为该服务不足的人群进行较大的介入试验的基础。