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

Area of Science:

• Microbiology and Immunology
• Host-Microbe Interactions
• Infectious Diseases

Background:

• Vaginal microbiota dysbiosis, often lacking Lactobacillus, increases urogenital infection risk.
• Mechanisms of Lactobacillus-mediated protection against urogenital pathogens remain unclear due to limited in vivo models.
• Existing mouse models do not accurately reflect the complexity of the human vaginal microbiota.

Approach:

• 16S rRNA amplicon sequencing was used to characterize vaginal microbiota in conventional and humanized microbiota mice (HMb mice).
• HMb mice were challenged with urogenital pathobionts, including Group B Streptococcus (GBS), Prevotella bivia, and uropathogenic E. coli.
• In vitro and in vivo assays were performed to assess the anti-pathogen activity of specific bacterial isolates from HMb mice.

Key Points:

• HMb mice exhibit a more human-like vaginal microbiota, with distinct community state types (h mCST).
• HMb mice demonstrated reduced susceptibility to uterine GBS and P. bivia colonization compared to conventional mice.
• Vaginal Enterobacteriaceae and Lactobacillus in HMb mice correlated with the absence of uterine GBS.
• HMb-derived E. coli, but not L. murinus, conferred protection against vaginal GBS burden in vivo.

Conclusions:

• The HMb mouse model provides a more accurate platform for studying the role of the vaginal microbiota in protection against urogenital pathogens.
• This model can elucidate mechanisms of microbial protection and facilitate the testing of novel probiotic strategies.
• Environmental factors significantly influence vaginal microbiome composition, highlighting the need for standardized models.