Methods to Test the Role of Age-related Lifestyle and Vaginal Microenvironment Changes and the Prevention, Treatment, and Progression of Genitourinary Syndrome of Menopause
测试与年龄相关的生活方式和阴道微环境变化以及更年期泌尿生殖综合征的预防、治疗和进展的作用的方法
基本信息
- 批准号:10091738
- 负责人:
- 金额:$ 66.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAffectAgeAgingAlcohol consumptionAnaerobic BacteriaAnti-Inflammatory AgentsArchivesAtrophicBacteriaBiochemicalBiogenic AminesBiologicalBiological AgingBiological MarkersBiology of AgingBiometryBody mass indexCellsChronicChronic DiseaseClinicalCodeCollectionComplexComputer softwareDataData AnalysesDevelopmentEpidemiologyEpithelialEstrogen TherapyEstrogensFundingGenitourinary System InfectionGenitourinary systemGenomicsGlycogenGoalsGrowth FactorGynecologyHuman PapillomavirusImmuneImmunologic MarkersImmunologyInflammagingInterventionKynurenineLactic acidLactobacillusLeadLife StyleLinkLower urinary tractLubricantsMachine LearningMeasuresMediatingMediationMenopausal SymptomMenopausal SyndromeMenopauseMetabolicMethodsMicrobiologyModelingModernizationMolecularMolecular TargetNational Institute on AgingOutcomePerimenopausePlayPostmenopausePreventionPrevotellaProbioticsProductionPropertyProspective StudiesPublic HealthQuality of lifeRecording of previous eventsReportingRiskRoleSamplingSex BehaviorSexual DysfunctionSigns and SymptomsSmokingStatistical MethodsStreptococcusStructural ModelsStructureSymptomsSystemSystems BiologyTaurineTestingTimeUnited States National Institutes of HealthVaginaVisitVulvaWomanWomen&aposs Healthage relatedagedanalytical methodbiological specimen archivescervicovaginalchemokinecohortcostcytokinedietary supplementsdysbiosishealthy aginghormonal contraceptionhormone therapyinfection riskinnovationlifestyle factorsmicrobialmicrobiomemicrobiome compositionmicrobiome researchmicrobiotamicrobiota metabolitesmodifiable lifestyle factorsmultiple omicsnovelnovel strategiesnovel therapeuticspathogenpreventrepositoryside effectstatisticstherapy developmenturogenital tractvaginal drynessvaginal lactobacillivaginal microbiota
项目摘要
Over 50% of postmenopausal women are affected by the genitourinary syndrome of menopause (GSM), a
progressive, chronic condition related to estrogen decline that includes vaginal atrophy, vaginal dryness,
reduced sexual desire, and other signs and symptoms. GSM symptoms are a costly public health concern and
worsen if untreated. Estrogen decline in menopause is thought to lead to reduced accumulation of vaginal
glycogen and shifts in vaginal microbiota. These include low vaginal Lactobacillus spp. levels in 50-80% of
postmenopausal women. Lactobacillus spp. protect the urogenital tract from pathogens in part by lactic acid
production and hypothesized anti-inflammatory properties, but whether lactobacilli play a functional role in
GSM is unknown. Available treatments for vulvovaginal GSM symptoms have limitations. Some women are
contraindicated for hormonal therapy or are concerned about side effects. While vaginal lubricants provide
some relief, many are toxic to the vaginal epithelium, reduce lactobacilli, and raise urogenital infection risk.
Thus, new ways to treat and prevent GSM are needed. Because lactobacilli are often reduced in menopause,
vaginal microbiota are plausible treatment targets; however, probiotics alone have not been proven effective.
Also, age-related changes in vaginal microbiota co-vary with metabolite and immune profiles; but, the cross-
talk between these molecular features and their role in GSM is unknown. We hypothesize that core vaginal
micro-environment biomarkers (VMB; e.g., microbial, metabolite, and immune profiles) reflect vaginal biological
aging (V-BA) that increases in menopause but may be modifiable by lifestyle factors. Prospective studies are
needed to identify core age-related VMB and determine how they affect GSM. To achieve this goal, we will
leverage 2,301 archived cervicovaginal samples collected from 812 women aged 35-60 years with clinical
visits every six months for two years (R01-CA123467). Specific Aims are to 1) quantify V-BA using VMB; 2)
evaluate the longitudinal relationship between V-BA and GSM; 3) longitudinally assess the relationship of
lifestyle factors on V-BA and VMB; 4) quantify longitudinal mediation by V-BA and VMB between lifestyle and
GSM. Microbiota are already profiled by 16S rRNA gene amplicon sequencing (R21-AI107224). We will
quantify concentrations of 70 immune markers (cytokines, chemokines, growth factors) and metabolites
(GC/LC-MS) in cervicovaginal samples. A novelty of this proposed project is that we will develop, validate, and
apply new statistical methods for complex longitudinal data that refine and adapt modern structural modeling
and compositional microbiome data analyses. These methods will provide a rigorous framework to handle
missing data and confounding that has been a major limitation in many microbiome studies. The ultimate public
health impact is that findings from this project have potential to inform development of new therapy to prevent
or treat GSM to promote women’s health. Our team has the expertise in biostatistics, epidemiology, aging,
gynecology, genomics, microbiology, and immunology required for this systems-biology approach to GSM.
超过50%的绝经后妇女受到更年期泌尿生殖系统综合征(GSM)的影响
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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REBECCA M. BROTMAN其他文献
REBECCA M. BROTMAN的其他文献
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{{ truncateString('REBECCA M. BROTMAN', 18)}}的其他基金
Cervicovaginal microbiome, mucosal immunity, and pathogen factors that contribute to spontaneous clearance of Chlamydia trachomatis
宫颈阴道微生物群、粘膜免疫和有助于沙眼衣原体自发清除的病原体因素
- 批准号:
10463072 - 财政年份:2022
- 资助金额:
$ 66.04万 - 项目类别:
Cervicovaginal microbiome, mucosal immunity, and pathogen factors that contribute to spontaneous clearance of Chlamydia trachomatis
宫颈阴道微生物群、粘膜免疫和有助于沙眼衣原体自发清除的病原体因素
- 批准号:
10631994 - 财政年份:2022
- 资助金额:
$ 66.04万 - 项目类别:
Methods to Test the Role of Age-related Lifestyle and Vaginal Microenvironment Changes and the Prevention, Treatment, and Progression of Genitourinary Syndrome of Menopause
测试与年龄相关的生活方式和阴道微环境变化以及更年期泌尿生殖综合征的预防、治疗和进展的作用的方法
- 批准号:
10475571 - 财政年份:2021
- 资助金额:
$ 66.04万 - 项目类别:
Methods to Test the Role of Age-related Lifestyle and Vaginal Microenvironment Changes and the Prevention, Treatment, and Progression of Genitourinary Syndrome of Menopause
测试与年龄相关的生活方式和阴道微环境变化以及更年期泌尿生殖综合征的预防、治疗和进展的作用的方法
- 批准号:
10675518 - 财政年份:2021
- 资助金额:
$ 66.04万 - 项目类别:
Methods to Test Lifestyle, Vaginal Microenvironment, and Genitourinary Symptoms across Menopause Transition
测试更年期过渡期间生活方式、阴道微环境和泌尿生殖系统症状的方法
- 批准号:
10229293 - 财政年份:2020
- 资助金额:
$ 66.04万 - 项目类别:
Longitudinal Study of the Vaginal Microbiome Prior To Incident STI
性传播感染发生前阴道微生物组的纵向研究
- 批准号:
8963646 - 财政年份:2015
- 资助金额:
$ 66.04万 - 项目类别:
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 - 财政年份:2013
- 资助金额:
$ 66.04万 - 项目类别:
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:
8568384 - 财政年份:2013
- 资助金额:
$ 66.04万 - 项目类别:
Molecular Epidemiology of the Vaginal Microbiome
阴道微生物组的分子流行病学
- 批准号:
8042549 - 财政年份:2010
- 资助金额:
$ 66.04万 - 项目类别:
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