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Socioeconomic and microenvironmental factors associated with the vaginal microbiota throughout the adult lifespan

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2023
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dissertation
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Approximately 84% of menopausal women experience symptoms and signs of the genitourinary syndrome of menopause (GSM), including vaginal dryness and vulvovaginal atrophy. During peri- and postmenopause, decreased estrogen is often accompanied by alterations of the vaginal microbiota and a perturbed local immune environment. While the vaginal microbiota is known to be dynamic in premenopause, temporal dynamics are understudied in menopause, and shifts toward profiles deficient in protective Lactobacillus spp. (with higher abundance of other anerobic and aerobic bacteria) may increase risk of gynecologic infections and GSM. Immune biomarkers have not been assessed with GSM while considering the composition of the vaginal microbiota. Socioeconomic status (SES), race, and ethnicity also impact the vaginal microbiota. While a single variable for race is often included in microbiome studies, few have evaluated contextual socioeconomic mechanisms. In this dissertation, Aim 1 compared the vaginal microbial longitudinal dynamics (characterized by 16S rRNA gene sequencing of mid-vaginal samples collected twice weekly) of pre-, peri-, and postmenopausal participants in an 8-week cohort. Bacterial community stability, as measured by longitudinal clustering of vaginal community state types (CSTs), Yue-Clayton similarity indices, and other metrics, was comparable by reproductive stage. Aim 2 involved a case-control study of GSM cases and age- and CST-matched controls. Cervical specimens were used to quantify concentrations of 70 immune markers. A proinflammatory state, defined as having at least three of seven predetermined analytes (IL-1β, IL-8, IL-23, MIP-1α, MIP-1β, IP-10, and RANTES) in the upper quartile, was associated with higher odds of GSM. A network analysis also revealed a cluster with proinflammatory IL-17F and IL-31 as its hubs in association with GSM. Aim 3 examined how the vaginal microbiota of participants enrolled in a cohort study differed by a composite score of individual- and neighborhood-level SES factors. Participants classified in the lowest SES score tertile displayed higher odds of a profile characterized by low Lactobacillus spp. abundance compared to those in the upper tertiles, even after adjustment for race and ethnicity. These findings contribute to the understanding of compositional differences in the vaginal microenvironment of diverse women and identify molecular targets for treatment and/or prevention of GSM.

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University of Maryland, Baltimore, School of Medicine, Ph.D. 2023.
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