Socioeconomic and Microenvironmental Factors Associated with the Vaginal Microbiota in Peri- and Post- Menopausal Women

项目摘要 在这个重新提交的论文项目描述提出了原创性的研究问题，并利用 分子流行病学的创新方法，以调查老年妇女的阴道微环境。 在美国，绝经期妇女的人口在不断增长。 女性的泌尿生殖系统症状包括阴道干涩和外阴阴道疼痛。本文 研究阴道细菌和免疫标记物如何与泌尿生殖系统症状相关， 绝经期和绝经后妇女。本论文还试图揭示如何差异，在阴道 老年妇女的微观环境因社会经济地位而异。这一建议的老龄化 研究论文奖，以增加多样性计划公告（R36）的重点是关键老化- 并促进老龄化流行病学和分子流行病学方面的培训。 阴道微生物群，主要是乳酸杆菌属，在防止殖民化方面发挥重要作用， 病原微生物，包括尿路感染和性传播感染，以及 保持妇女的妇科和生殖健康。阴道免疫微环境是 它深受性激素（包括雌激素）的影响，并与微生物共同进化，以维持一种 宿主与微生物的稳态关系在育龄妇女中，阴道乳酸杆菌的消耗，如 在细菌性阴道病（BV）的临床诊断中，可引起包括阴道炎在内的不良症状。 排出物和恶臭。然而，对女性外阴阴道症状的分子线索知之甚少， 绝经期泌尿生殖系统综合征（GSM）。此外，很少有研究仔细评估了潜在的 社会经济机制，包括教育、收入和邻里特征， 组合，可能有助于解释BV，STI和GSM中已知的种族/民族差异。该项目将填补 与绝经和SES在塑造阴道微生物群中的作用有关的关键知识空白。 本文的具体目标是确定：1）GSM之间的时变关联 绝经期和绝经后妇女10周内的症状和阴道微生物群组成 观察性研究; 2）GSM和阴道细胞因子/趋化因子水平之间的关联， 绝经期和绝经后妇女的阴道微生物群匹配病例对照研究; 3）阴道 使用SES因素的复合指数，绝经后和绝经后妇女的微生物群因SES而异， 大型横断面研究。R36将利用现有的微生物群和免疫数据进行有效的研究， 新的目标和分析与母研究不重叠。为了实现研究目标， 国家老龄化研究所，以确定影响微生物组组成和功能的因素， 老化过程中的特征，这项工作将评估阴道微环境中的成分差异 不同的绝经期妇女和确定治疗和/或预防GSM的分子靶点。

PROJECT SUMMARY The dissertation project described in this re-submission proposes original research questions and utilizes innovative methods in molecular epidemiology to investigate the vaginal microenvironment of older women. Menopausal women are a growing population in the U.S. A major morbidity that affect post-menopausal women is genitourinary symptoms, including vaginal dryness and vulvovaginal pain. This dissertation investigates how vaginal bacteria and immunologic markers are associated with genitourinary symptoms in peri- and postmenopausal women. This dissertation also seeks to reveal how disparities in the vaginal microenvironment for older women vary by socioeconomic statuses (SES). This proposal to the Aging Research Dissertation Awards to Increase Diversity Program Announcement (R36) focuses on key aging- related health concerns and facilitates training in epidemiology of aging and molecular epidemiology. Vaginal microbiota, dominated by Lactobacillus spp., play an important role in preventing colonization by pathogenic organisms, including urinary tract infections and sexually transmitted infections (STIs), and maintain a woman’s gynecologic and reproductive health. The vaginal immunologic microenvironment is profoundly influenced by sex hormones, including estrogens, and has co-evolved with microbes to maintain a homeostatic host-microbial relationship. In reproductive-aged women, depletion of vaginal lactobacilli, such as in the clinical diagnosis of bacterial vaginosis (BV), can cause undesirable symptoms including vaginal discharge and malodor. However, less is known about the molecular cues of vulvovaginal symptoms in the genitourinary syndrome of menopause (GSM). Further, few studies have carefully evaluated the underlying socioeconomic mechanisms, including education, income, and neighborhood characteristics, that, in combination, may help to explain known racial/ethnic disparities in BV, STIs, and GSM. This project will fill critical knowledge gaps related to the role of menopause and SES in shaping the vaginal microbiota. The specific aims of this dissertation are to determine: 1) the time-varying associations between GSM symptoms and the composition of the vaginal microbiota of peri- and postmenopausal women in a 10-week observational study; 2) the association between GSM and vaginal cytokine/chemokine levels in an age- and vaginal microbiota-matched case-control study of peri- and postmenopausal women; and 3) how vaginal microbiota of peri- and postmenopausal women differ by SES using a composite index of SES factors in a large cross-sectional study. The R36 will leverage existing microbiota and immune data for efficient research, and the novel aims and analyses do not overlap with the parent studies. In keeping with a research objective of the National Institute on Aging, to define the factors that influence microbiome composition and functional characteristics during aging, this work will evaluate compositional differences in the vaginal microenvironment of diverse menopausal women and identify molecular targets for treatment and/or prevention of GSM.