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

Vaginal microbial composition is associated with differential risk of urogenital infection. Although Lactobacillus spp. are thought to confer protection against infection, the lack of in vivo models resembling the human vaginal microbiota remains a prominent barrier to mechanistic discovery. Using 16S rRNA amplicon sequencing of C57BL/6J female mice, we found that vaginal microbial composition varies within and between colonies across three vivaria. Noting vaginal microbial plasticity in conventional mice, we assessed the vaginal microbiome of humanized microbiota mice ((HMb)mice). Like the community structure in conventional mice, (HMb)mice vaginal microbiota clustered into community state types but, uniquely, (HMb)mice communities were frequently dominated by Lactobacillus or Enterobacteriaceae. Compared to conventional mice, (HMb)mice were less susceptible to uterine ascension by urogenital pathobionts group B Streptococcus (GBS) and Prevotella bivia. Although Escherichia and Lactobacillus both correlated with the absence of uterine GBS, vaginal pre-inoculation with exogenous (HMb)mouse-derived E. coli, but not Ligilactobacillus murinus, reduced vaginal GBS burden. Overall, (HMb)mice serve as a useful model to elucidate the role of endogenous microbes in conferring protection against urogenital pathogens.