<i>Akkermansia muciniphila</i> impacts group B <i>Streptococcus</i> vaginal colonization

<i>Streptococcus agalactiae,</i> or group B <i>Streptococcus</i> (GBS), is an opportunistic pathogen that asymptomatically colonizes the vaginal tract of up to 30% of healthy individuals. However, during pregnancy, it is associated with adverse pregnancy outcomes, and GBS can be transmitted to the fetus <i>in utero</i> or the newborn during vaginal birth, resulting in invasive neonatal disease. Previously, we identified that <i>Akkermansia muciniphila</i> increases GBS vaginal persistence in a cohort of human vaginal microbiome samples collected throughout pregnancy and promotes GBS vaginal colonization in a murine model. However, the mechanisms responsible for these observations are unknown. Here, we analyze additional vaginal shotgun metagenomic data sets and show that across independent studies with diverse populations, <i>A. muciniphila</i>-positive samples had higher GBS abundance. We determined that <i>A. muciniphila</i> aggregates with human vaginal isolates of GBS across all serotypes and promotes GBS attachment to human vaginal epithelial cells (hVECs). RNA-sequencing analysis reveals that <i>A. muciniphila</i> changed the expression of 281 unique GBS genes during hVEC co-colonization, many of which are involved in cell wall/membrane/envelope biogenesis. We demonstrate the importance of the GBS capsule and pili for direct interaction with <i>A. muciniphila</i> and increased attachment to hVECs, respectively. Lastly, we found that <i>A. muciniphila</i> promoted GBS aggregation in the murine vaginal lumen and that continual treatment with <i>A. muciniphila</i> reduced GBS vaginal persistence. Our results provide mechanistic insights and further evidence of the impact of <i>A. muciniphila</i> on GBS vaginal colonization and also demonstrate a beneficial potential of <i>A. muciniphila</i> treatment in the vaginal environment.IMPORTANCEGroup B <i>Streptococcus</i> (GBS) is a frequent colonizer of the vaginal tract of healthy people; however, during pregnancy, maternal colonization is associated with adverse pregnancy outcomes. GBS is a leading cause of neonatal sepsis and meningitis, with transmission to neonates occurring either during vaginal delivery or through ascension into the uterus during pregnancy. The influence of the vaginal microbiota on GBS pathogenesis remains greatly underappreciated. We have found that GBS is associated with the mucin-degrading intestinal commensal <i>Akkermansia muciniphila</i>, a newly identified colonizer of the vaginal tract. Our research identifies the mechanistic impact of this commensal organism on GBS aggregation, cell adherence, and gene expression, as well as its therapeutic potential during GBS vaginal colonization. Unraveling relationships between GBS and the vaginal microbiota will improve maternal-fetal health and may facilitate the development of alternative methods to reduce GBS <i>in utero</i> complications and neonatal disease.