Vaginal Microbiome and Metabolites in Preterm Birth

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PROJECT SUMMARY/ABSTRACT This proposal presents a five year research career development program focused on the study of vaginal microbiome contributions to preterm birth among women with HIV to expand the breadth and depth of understanding of vaginal dysbiosis in preterm birth (PTB). The candidate is currently an Assistant Professor of Gynecology and Obstetrics at Johns Hopkins University School of Medicine. The outlined proposal builds on the candidate’s previous research and clinical experience in pregnancy outcomes among women with HIV and integrates two new domains of expertise of her mentors, Drs. Irina Burd and Khalil Ghanem at Johns Hopkins: inflammatory pathways leading to PTB with vaginal microbiome research. The proposed experiments and didactic work will position the candidate with a unique set of cross disciplinary skills that will enable her to transition to independence as a physician scientist with expertise in cohort study design and microbiome bioinformatics. Bacterial vaginosis (BV), an alteration in the vaginal microbiome, nearly doubles the risk of preterm birth, delivery prior to 37 weeks, and affects one third of women of reproductive age. In the US, women with HIV experience a two-fold increased risk of PTB compared to women without HIV. Women with HIV who have a Lactobacilus-deficient/ anaerobe-dominant vaginal microbiota have increased vaginal inflammation, higher genital HIV viral load and increased HIV viral shedding. The lacking data in US-based pregnant women with HIV risk perpetuating significant healthcare disparities. It is unknown whether the underlying mechanism between HIV infection and PTB is driven by vaginal dysbiosis. The foundation of this proposal is based on prior data documenting vaginal dysbiosis as a potential driver for altered inflammatory pathways and adverse pregnancy outcomes, particularly among African American women. Women with HIV and vaginal dysbiosis have increased risk for genital mucosa inflammation and viral shedding. The role of vaginal dysbiosis in pregnancy among women with HIV has not been explored to date, nor have the effects of ART on the vaginal microbiome in pregnancy. Specifically, this proposal aims to: 1) compare the structure (relative and absolute abundance) and composition (diversity) of the vaginal microbiota of pregnant women with HIV who experience PTB versus term birth, 2) determine the extent to which vaginal microbiota function, measured by median difference in metabolites (short chain fatty acids), correlates with PTB, and 3) measure and compare cervico- vaginal concentrations of soluble inflammatory mediators (antimicrobial peptides and pro-inflammatory cytokines) in PTB. The scientific objective of this proposal is to begin to define the strength of the association between vaginal microbiota, markers of mucosal inflammation and PTB among women with HIV and generate hypotheses that inform the direction and design of subsequent studies focused on potential interventions.