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

项目总结 本次重新提交的论文项目提出了原创性的研究问题，并利用 分子流行病学研究老年妇女阴道微环境的创新方法。 在美国，更年期妇女是一个不断增长的人口。这是影响绝经后妇女的主要发病率 女性的泌尿生殖系统症状包括阴道干燥和外阴阴道疼痛。本论文的主要内容是 研究阴道细菌和免疫标记物与泌尿生殖系统症状之间的关系 围绝经期和绝经后妇女。这篇论文还试图揭示阴道中的差异如何 老年妇女的微环境因社会经济地位(SES)而异。这项针对老年人的建议 增加多样性计划的研究论文奖公告(R36)侧重于关键的老化- 与健康有关的问题，并促进老龄流行病学和分子流行病学方面的培训。 以乳杆菌属为主的阴道微生物区系在防止细菌定植中起着重要作用。 病原体，包括尿路感染和性传播感染；以及 维护女性的妇科和生殖健康。阴道免疫微环境是 深受包括雌激素在内的性激素的影响，并与微生物共同进化，以保持 动态平衡的宿主-微生物关系。在育龄妇女中，阴道乳杆菌的枯竭，如 在细菌性阴道病(BV)的临床诊断中，可引起包括阴道在内的不良症状 排泄物和异味。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潜在的 社会经济机制，包括教育、收入和社区特征，在 结合起来，可能有助于解释BV、性传播感染和GSM中已知的种族/民族差异。这个项目将填补 与更年期和SES在塑造阴道微生物区系中的作用有关的关键知识差距。 本文的具体目的是确定：1)GSM之间的时变关联 围绝经期和绝经后妇女10周的症状和阴道微生物区系组成 观察性研究；2)GSM与同一年龄段阴道细胞因子/趋化因子水平的相关性 围绝经期和绝经后妇女阴道微生物区系匹配的病例对照研究；3)阴道 围绝经期和绝经后妇女的微生物区系存在SES的差异，使用SES因素的综合指数 大型横断面研究。R36将利用现有的微生物区系和免疫数据进行有效的研究， 小说的目的和分析并不与父辈的研究重叠。与以下研究目标保持一致 国家老龄研究所，以确定影响微生物组组成和功能的因素 在衰老过程中的特征，这项工作将评估阴道微环境中的成分差异 对不同的更年期妇女进行研究，并确定治疗和/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.