Utility of human milk oligosaccharides against the perinatal pathogen, Group B Streptococcus

Project Summary Adverse pregnancy outcomes are a global issue that affects more than 50 million people per year. Infections during gestation contribute significantly to adverse pregnancy outcomes, such as preterm birth and neonatal sepsis. Streptococcus agalactiae or Group B Streptococcus (GBS) is a major cause of ascending vaginal and intrauterine infection during pregnancy. To initiate infection, GBS must colonize the vagina and initiate a robust biofilm to turn the vaginal mucosa into a replicative niche. Subsequently, GBS ascends the reproductive tract in an undefined process to invade the gestational membranes, cross the placenta, and infect the amniotic cavity and the fetus. Currently, there is no commercially available vaccine against GBS to prevent its cognate disease outcomes. However, epidemiological data has indicated that exposure to maternal breast milk is associated with protection against GBS infection of the neonate. We have new and exciting data to suggest that components of human breast milk, such as human milk oligosaccharides (HMOs), have antibiofilm activity against GBS. Given this, we hypothesize that treatment with HMOs could lead to decreased GBS biofilm formation, colonization, invasive infection cognate inflammation, microbiome disruption, and disease progression. We will test this by determining the contribution of HMOs on bacterial and immunological responses in primary human placental macrophages, an organ-on-a-chip infection model, ex vivo gestational membrane model, vaginal tissue models and a mouse model of infection during pregnancy. This work will help us establish the efficacy of deployment of prebiotic HMOs as a cost-effective dietary or chemotherapeutic strategy against GBS which may improve pregnancy outcomes in vulnerable groups.