Human milk oligosaccharides reduce murine group B Streptococcus vaginal colonization with minimal impact on the vaginal microbiota

Abstract

Group B Streptococcus (GBS) colonizes the vaginal mucosa of a significant percentage of healthy women and is a leading cause of neonatal bacterial infections. Currently, pregnant women are screened in the last month of pregnancy and GBS-positive women are given antibiotics during parturition to prevent bacterial transmission to the neonate. Recently, human milk oligosaccharides (HMOs) isolated from breastmilk were found to inhibit GBS growth and biofilm formation in vitro, and women that make certain HMOs are less likely to be vaginally colonized with GBS. Using in vitro human vaginal epithelial cells and a murine vaginal colonization model, we tested the impact of HMO treatment on GBS burdens and the composition of the endogenous microbiota by 16S rRNA amplicon sequencing. HMO treatment reduced GBS vaginal burdens in vivo with minimal alterations to the vaginal microbiota. HMOs displayed potent inhibitory activity against GBS in vitro, but HMO pretreatment did not alter adherence of GBS or the probiotic Lactobacillus rhamnosus to human vaginal epithelial cells. Additionally, disruption of a putative GBS glycosyltransferase (Δsan_0913) rendered the bacterium largely resistant to HMO inhibition in vitro and in vivo but did not compromise its adherence, colonization, or biofilm formation in the absence of HMOs. We conclude that HMOs are a promising therapeutic bioactive to limit GBS vaginal colonization with minimal impacts on the vaginal microenvironment.

Vaginal microbial dynamics and pathogen colonization in a humanized microbiota mouse model

“…2). This finding suggests that host selective pressures drive the vaginal community towards a skewed dominance of a single organism independent of microbial exposure (23)(24)(25). We observed high variability between cohorts of HMb mice sampled at different times from the same colony, but this variability could still be grouped into consistent h mCSTs (Fig.…”

“…; however, there remain several limitations to this model. There is likely some "conventionalization" of HMb mice since we detected a S. succinus-dominant community ( h mCST II) which is the most common community present in conventional C57BL/6J Jackson mice (23,24).…”

“…Like prior studies, mice from Jackson Labs were primarily dominated by Staphylococcus succinus and Enterococcus spp. (23,24), with occasional appearance of Lactobacillus spp., Corynebacterium spp., or Acinetobacter spp. dominant communities (Fig.…”

“…Vaginal samples across cohorts were hierarchically clustered into murine community state types using Ward's linkage of Euclidean distances as done previously (23,24).…”

“…Staphylococcus succinus and Enterococcus spp. are the most common members in C57BL/6J mice (23,24), Enterobacteriaceae and Proteus spp. are dominant in CD-1 mice (25), and Streptococcus spp.…”