Vaginal microbiota, immune responses and vulvovaginal symptoms during menopause

更年期期间的阴道微生物群、免疫反应和外阴阴道症状

基本信息

批准号：
8568384
负责人：
REBECCA M. BROTMAN
金额：
$ 18.76万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-15 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8568384
关键词：
Address Adverse effects Affect Age Aging Anti-Inflammatory Agents Anti-inflammatory Archives Atrophic Bacteria Behavioral Bioinformatics Breast Burn injury Categories Cervical Chemicals Clinical Cohort Studies Coitus Communities Coronary Arteriosclerosis DNA Data Deposition Deterioration Disease Dryness Dyspareunia Educational workshop Enrollment Epidemiology Epithelium Estrogen Therapy Estrogens Event Female Funding Future Genital system Genitourinary system Genomics Glycogen Gonadal Steroid Hormones Growth Factor Guidelines Gynecologic Gynecology Health Hemorrhage Hormonal Human Human Papillomavirus Human body Immune response Immune system Immunoassay Immunologic Markers Immunologics Indigenous Individual Inflammatory Intervention Lactic acid Lactobacillus Lead Link Liver Longevity Lubricants Menopause Methods Microbe Microbiology Mission Pain Participant Patient Self-Report Perimenopause Play Postmenopause Probiotics Prospective Studies Protein Array Proteins Pruritus Quality of life Recording of previous events Recruitment Activity Relative (related person)Reporting Research Resources Role Route Sampling Sex Functioning Sexual Health Site Specimen Staging Stroke Swab Symptoms Therapeutic Tissues United States National Institutes of Health Urination Vagina Vaginal Discharge Venous Visit Woman Women&apos s Health aged antimicrobial base chemokine commensal microbes common treatment cytokine dosage experience follow-up hormone therapy improved inflammatory marker irritation malignant breast neoplasm microbial microbial community microbial host microbiome multidisciplinary novel strategies organic acid pathogen public health relevance rRNA Genes repository reproductive resilience statistics

项目摘要

DESCRIPTION (provided by applicant): Studies demonstrate that between 25-50% of menopausal women report vulvovaginal symptoms including vaginal dryness, irritation, burning, itching, and dyspareunia, all of which severely affect quality of life. As women approach menopause, decreased estrogen levels are accompanied by changes in the vagina including decreased glycogen accumulation in the epithelium, increased pH, and deterioration of vaginal tissues, which lead to symptoms of vaginal discomfort. Hormone therapy is the primary treatment for vulvovaginal symptoms in menopausal women, however it is contraindicated in some women. Non-hormonal therapeutic approaches for improving symptoms and quality of life in postmenopausal women have not been well studied. The vaginal microbial communities (termed the vaginal microbiota) play a critical role in protecting the female genital tract from disease; however, surprisingly little is known about the composition of vaginal bacteria across the different stages of menopausal transition, how they differ between individuals, the correlation with vaginal immunologic microenvironment, or the associations with gynecologic complaints and sexual functioning. Between 2009-2012, 885 women aged 35-60 years were enrolled in a prospective study of menopause transition and followed every six months for two years (R01-CA123467). Taking advantage of that resource, the proposed study will utilize 2500 longitudinal vaginal samples stored in a freezer archive to address the following three specific aims: (1) To describe the changes in the vaginal microbiota by age and stage of menopause over a 2-year period, (2) To evaluate the association between the vaginal microbiota and vulvovaginal complaints and (3) To assess the correlation between the vaginal immunologic microenvironment with the microbiota. Participants were categorized according to menopausal categories by the Stages of Reproductive Aging Workshop (STRAW) guidelines. The vaginal microbiota will be characterized using 16S rRNA gene analysis amplified from whole genomic DNA isolated from clinician-collected mid-vaginal swabs. Cervical secretions will be used to quantify concentrations of 27 different immune markers (cytokines, chemokines, and growth factors) using multiplexed bead-based immunoassays with total protein adjustment. By bringing together multidisciplinary expertise in bioinformatics, epidemiology, genomics, gynecology, microbiology and statistics, this study will be able to provide critical descriptive data on (1) differences in the composition and stability of the vaginal microbiome by menopausal stage, (2) association between microbial changes and presence of vulvovaginal complaints, and (3) the possible correlation between vulvovaginal microbial and immunologic microenvironmental changes during the menopausal transition. These data will be used to evaluate the potential for non-hormonal, anti-inflammatory, or probiotic interventions for the treatment of common vulvovaginal complaints in peri- and postmenopausal women.

描述（由申请人提供）：研究表明，25-50% 的更年期女性有外阴阴道症状，包括阴道干燥、刺激、灼烧感、瘙痒和性交痛，所有这些都严重影响生活质量。当女性接近更年期时，雌激素水平下降会伴随着阴道的变化，包括上皮糖原积累减少、pH值升高和阴道组织恶化，从而导致阴道不适的症状。激素疗法是更年期女性外阴阴道症状的主要治疗方法，但对某些女性来说是禁忌的。用于改善绝经后妇女症状和生活质量的非激素治疗方法尚未得到充分研究。阴道微生物群落（称为阴道微生物群）在保护女性生殖道免受疾病侵害方面发挥着关键作用；然而，令人惊讶的是，人们对绝经过渡不同阶段阴道细菌的组成、它们在个体之间的差异、与阴道免疫微环境的相关性或与妇科疾病和性功能的关系知之甚少。 2009 年至 2012 年间，885 名 35-60 岁的女性参加了一项更年期过渡的前瞻性研究，并每六个月进行一次随访，持续两年 (R01-CA123467)。利用该资源，拟议的研究将利用储存在冰箱档案中的 2500 个纵向阴道样本来实现以下三个具体目标：（1）描述两年内按年龄和绝经阶段划分的阴道微生物群的变化期间，（2）评估阴道微生物群与外阴阴道不适之间的关联，（3）评估阴道免疫微环境与微生物群之间的相关性。生殖衰老阶段研讨会 (STRAW) 指南根据更年期类别对参与者进行分类。将使用 16S rRNA 基因分析来表征阴道微生物群，该分析从临床医生收集的阴道中部拭子中分离出的全基因组 DNA 中扩增而来。宫颈分泌物将用于通过基于微珠的多重免疫分析和总蛋白调整来量化 27 种不同免疫标记物（细胞因子、趋化因子和生长因子）的浓度。通过汇集生物信息学、流行病学、基因组学、妇科、微生物学和统计学等多学科专业知识，这项研究将能够提供以下方面的关键描述性数据：(1) 绝经期阴道微生物组的组成和稳定性差异，(2) 关联性微生物变化与外阴阴道不适之间的关系，以及（3）外阴阴道微生物与免疫微环境变化之间可能的相关性更年期过渡。这些数据将用于评估非激素、抗炎或益生菌干预措施治疗围绝经期和绝经后妇女常见外阴阴道疾病的潜力。