The long-term objectives of the GLO VIP project are to define the virome of the female reproductive tract longitudinally before, during and after pregnancy, and to assess its relationship to preterm birth (PTB) and other adverse pregnancy outcomes. The study will employ three extant cohorts generated from our previous studies: 1) a cohort of ~1000 pregnant women who participated in our Vaginal Human Microbiome Project (VaHMP) which collected over 60,000 cross-sectional samples (cervical, vaginal, buccal, perianal, blood) from ~6500 visitors to our women?s clinics at the VCU Health Center; 2) a cohort of ~1000 pregnant women who participated in our Multi Omic Microbiome Study Pregnancy Initiative (MOMS PI) and were sampled longitudinally in VCU?s women?s clinics, Labor & Delivery, NICU, and Newborn Baby Clinic; and 3) a cohort of ~500 pregnant women who participated in MOMS PI but were sampled longitudinally at women?s clinics at Swedish Hospital, Yakima General Hospital, and the University of Washington Health Center. Approximately 150,000 longitudinal samples (cervical, vaginal, buccal, rectal, blood, urine, placenta, cord, cord blood, meconium and first stool) have been prepared for RNA, DNA, proteome, metabolome, and immunoproteome analyses. Slightly over 30% of the women in each of these cohorts experienced complicated pregnancies; e.g., 10-15% PTB, ~10% premature rupture of membranes (PROM) or preterm PROM (PPROM), ~20% hypertension, ~10% gestational diabetes, and ~5% pre-eclampsia. We have identified ~250 subjects (~150 with adverse outcomes) from the VaHMP cohort and ~240 (~200 with adverse outcomes) from the VCU cohort of MOMS PI for the discovery phase of this project, in which we will employ Whole Metagenome Sequencing (WMGS) and Whole Metatranscriptome Sequencing (WMTS) to characterize the DNA and RNA viromes, including both known and previously unknown viruses, of the female reproductive tract and probe for relationships between the virome and adverse pregnancy outcomes, and correlate the relationship between the bacterial microbiome, the virome, and health. Samples from participants (~100 with adverse outcomes) from the Seattle cohort of MOMS PI will be used in the validation phase of the study in which we will examine birth products and neonatal samples (meconium, buccal, first stool) for viral activity and replicate our results from the discovery phase of the project. In addition, we will characterize host responses in selected samples by metabolomics and immunoproteomic analysis of metabolyte and cytokine levels in blood and other relevant tissues from participants and neonates identified as of interest in the discovery phase of the project. Our results will provide both a comprehensive overview of the virome of the female reproductive tract and its impact on pregnancy, and indications of the role(s) of the virome in adverse pregnancy outcomes.
This project will identify and characterize the viruses, both known and unknown, that comprise the virome of the female reproductive tract. We will characterize differences between the viromes of pregnant and non-pregnant women, the impact of pregnancy on the virome, and the relationships of the virome to the bacterial microbiome and the host, using multiple omic strategies. Our overall goal is to identify relationships between the virome and the microbiome and adverse pregnancy and neonatal outcomes, with a particular focus on preterm birth.
