Impact of pregnancy and diet on the murine vaginal microbiota Raw sequence reads
Group B Streptococcus (GBS) is a leading cause of neonatal morbidity, mortality and preterm birth. In approximately 20 million women, GBS is a resident of the maternal vaginal microbiota and can be transmitted to the neonate during vaginal delivery or through in utero GBS invasion. Neonates born to mothers with gestational diabetes mellitus (GDM) have a 3.7 fold increased risk of GBS sepsis, but biological mechanisms are unknown. We hypothesize that gestational diabetes renders women and their neonates more susceptible to GBS by perturbing immune defenses and enhancing GBS virulence. To elucidate host and microbial factors that drive this increased susceptibility to GBS, we have developed an in vivo model of GBS reproductive tract ascension in mice with gestational diabetes induced by a high-fat-high-sucrose diet. Using this model, we performed integrative analysis of GBS burden and transmission, host and GBS global transcriptional profiling, reproductive tract cytokine and immune cell profiles, and longitudinal 16S rRNA amplicon sequencing of the vaginal microbiota during pregnancy. By collecting vaginal swabs every 3 days from diet introduction through E14 of pregnancy of mice from the pup outcomes and E17.5 experiments above, we longitudinally characterized the vaginal microbiota in this murine model with two primary objectives: A) to define how the murine vaginal microbiota changes throughout non-diabetic and diabetic pregnancy and B) to determine if there are signatures of vaginal communities that are protective or permissive against GBS in utero dissemination.