DOI
https://doi.org/10.25772/EDDT-1G77
Defense Date
2021
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Microbiology & Immunology
First Advisor
Kimberly Jefferson
Second Advisor
Jennifer Fettweis
Abstract
The vaginal microbiome is important in reproductive health and disease and is often dominated by lactobacilli. However, there are many other community state types dominated by single species that are still not well characterized. Bifidobacterium species such as Bifidobacterium breve and Bifidobacterium longum have been observed to dominate vaginal profiles. Bifidobacteria are important in infant gut development, but little is known about their role in vaginal health. Thus, we sought to use a multisystem approach to better characterize Bifidobacterium species present in the vaginal microbiome with an emphasis on B. breve. Eight strains of B. breve were isolated from vaginal samples and underwent bacterial whole genome sequencing. Phylogenetic and comparative genomic analyses were performed using 18 vaginal B. breve strains and 46 non-vaginal B. breve isolates from other human body sites. The phylogenetic results revealed three B. breve clades. Although all B. breve were closely related, one clade and a subgroup of a second clade were enriched in strains isolated from the vaginal environment. This study also identified two families of insertion sequences and a subset of proteins that were more prevalent in vaginal B. breve strains. These results may reflect the adaptation of B. breve to the vaginal environment. Through two 16S rRNA studies: 4,726 samples from the Vaginal Human Microbiome Project (VaHMP) and 2,058 samples from 597 participants in the Multi-Omic Microbiome Study-Pregnancy Initiative (MOMS-PI) pregnancy cohort, an extensive analysis was conducted on Bifidobacterium species within the vaginal microbiome. B. breve co-occurred with both pathogenic bacterial species and beneficial commensals. Women with vaginal microbiomes dominated by B. breve typically lacked symptoms and clinical signs of infection whereas women with any amount of B. breve were more likely to be diagnosed with trichomoniasis. These results suggest that B. breve may play different roles in health associated with different abundance levels in the vaginal microbiome. Lastly, the potential competitive role of B. breve compared to L. crispatus was further elucidated by performing biochemical and bioinformatic analyses. Biochemical analyses showed that some strains of B. breve produce bactericidal compounds comparable to L. crispatus 39G. In silico analyses also showed that B. breve is predicted to encode genes in pathways that may permit the production of hydrogen peroxide. This work furthers the support of the emerging concept that species other than lactobacilli can dominate the vaginal microbiome during health, and it reveals that some B. breve strains may be adapted to the vaginal environment. Additionally, the study suggests that some vaginal strains of B. breve may serve a protective role within the vaginal microbiome. This comprehensive study of vaginal B. breve provides insight into the evolutionary pressures between host and microbe, elucidates possible mechanisms by which the species likely thrive within different environments, and lays a foundation for understanding how Bifidobacterium impacts reproductive health in pregnancy and beyond.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
6-14-2021
Included in
Bioinformatics Commons, Computational Biology Commons, Other Microbiology Commons, Systems Biology Commons