Social Determinants and Vaginal Microbiome Effects on Preterm Birth in Hawaii

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PROJECT SUMMARY - Social Determinants and Vaginal Microbiome Effects on Preterm Birth in Hawaii Preterm Birth (PTB) (delivery of a neonate before 37 weeks gestation) occurs at high rates in Native Hawaiians and Pacific Islanders in Hawaii (NHPI), resulting in significant long term neonatal morbidity of their offspring. Strong biologic markers for PTB are present within the maternal vaginal microbiome. A particular signature of anaerobic species abundance, depletion of Lactobacillus crispatus, and predominance of Lactobacillus iners results in inflammatory cytokines and metabolites theorized to set off a molecular cascade leading to preterm labor. Women with Lactobacillus Crispatus predominance have a 75% lower risk of PTB compared those with vaginal microbial community primarily of Gardnerella or other anerobic species. However, ethnic variation also exists in vaginal microbiome composition, and it is unknown if this same high risk vaginal microbiome profile portends similar risk of PTB in NHPI communities. In addition to racial and ethnic variation, social determinants of health such as income, nutrition, access to healthcare, or effects of systemic racism also play a role in microbial community composition, and may subsequently contribute to PTB risk. The initial goal of this project is to establish vaginal microbiome profiles of women at risk for PTB in Hawaiʻi. The long-term goal is to create a point of care test to predict PTB using vaginal molecular signals, and understand inflammatory pathways affected by vaginal dysbiosis that could be modulated with targeted therapy to prevent PTB. As foundational steps toward this goal, our project will address the following Specific Aims: 1.) Compare vaginal microbial composition in women at risk of PTB among low-risk multiparous women. Hypothesis: Women who deliver preterm will have higher abundance of Lactobacillus iners or anerobic species along with inflammatory markers and associated metabolites in early pregnancy. Research Approach: Pregnant women at risk for PTB and healthy controls will collect vaginal swab samples during mid-gestation (14-22 weeks). 16S sequencing will be performed, alpha and beta diversity profiles assigned, and Community State Types (CSTs) or predominant species designated. From vaginal swabs, inflammatory cytokines levels will be measured with multi-plex ELISA; and metabolites measured with mass spectroscopy. These metrics will be compared among women who did and did not deliver preterm. 2.) Determine the association between social determinants of health and vaginal microbiota in women who do and do not experience PTB. Hypothesis: Increased social adversity and stress, unmitigated by resiliency (ability to endure hardship), leading to poor diet quality, are associated with increased vaginal microbial dysbiosis, and subsequent PTB. Research Approach: Participants will complete a compilation of surveys including questions pertaining to stress, anxiety, dietary intake, food insecurity, perceived racism and resiliency. Machine learning techniques will be used to identify a PTB risk pattern profile incorporating environmental exposures and predominant microbial species.