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

• 批准号: 8721849
• 负责人: REBECCA M. BROTMAN
• 金额: $ 23.43万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8721849
• 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; Data; Deposition; Deterioration; Disease; Dryness; Dyspareunia; Educational workshop; Enrollment; Epidemiology; Epithelium; Estrogen Therapy; Estrogens; Event; Female; Funding; Future; Genital system; Genitourinary system; Genomic DNA; Genomics; Glycogen; Gonadal Steroid Hormones; Growth Factor; Guidelines; Gynecologic; Gynecology; Health; Hemorrhage; High-Throughput Nucleotide Sequencing; 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' 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

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％的绝经妇女报告了外阴阴道症状，包括阴道干燥，刺激，燃烧，瘙痒，瘙痒和性交障碍，这都严重影响了生活质量。随着女性接近更年期，雌激素水平的降低伴随着阴道的变化，包括上皮中糖原积累的降低，pH值增加和阴道组织的恶化，这导致阴道不适的症状。激素治疗是对绝经女性外阴阴道症状的主要治疗方法，但是在某些女性中禁忌。在绝经后妇女改善症状和生活质量的非激素治疗方法尚未得到很好的研究。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的影响方面起着关键作用。然而，令人惊讶的是，关于在绝经的不同阶段的阴道细菌组成，个人之间的差异，与阴道免疫学微环境的相关性或与妇科申诉和性功能的关联。在2009年至2012年之间，有885名35-60岁的妇女参加了对更年期过渡的前瞻性研究，并每六个月进行两年（R01-CA123467）。利用该资源，拟议的研究将利用2500个存储在冰柜档案中的纵向阴道样本来解决以下三个特定目的：（1）描述按2年期间的年龄和更年期的阴道微生物群的变化（2）评估阴道微生物群和（3）的相关性（2），以评估阴道型和外阴疾病之间的相关性（3）与微生物群。根据生殖老化研讨会（Straw）指南的阶段，根据更年期类别对参与者进行了分类。阴道菌群将使用从临床医生收集的中拭子分离的整个基因组DNA扩增的16S rRNA基因分析来表征。宫颈分泌物将使用基于总蛋白质调节的多重珠子免疫测定法来量化27种不同的免疫标记（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，微生物学和统计学方面的多学科专业知识，这项研究将能够提供有关（1）阴道微生物组组成和稳定性差异的关键描述性数据。在更年期过渡期间，外阴阴道的微生物和免疫学微环境变化。这些数据将用于评估绝经期和绝经后妇女的共同外阴阴道投诉的非激素，抗炎或益生菌干预措施的潜力。