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

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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.