Characterization of the vaginal microbiome in pregnancy

Abstract

The vaginal microbiome plays an important role in women's reproductive health. Imbalances in this microbiota are associated with bacterial vaginosis, increased susceptibility to sexually transmitted infections, and negative reproductive outcomes. The causes of such variations, however, are poorly understood. A healthy vaginal microbiota is defined as Lactobacillus-dominated and an overgrowth of other species is often associated with unhealthy conditions. An appreciation of "atypical" microbiomes in healthy women, such as Bifidobacterium-dominated, has been gradually increasing. Although bifidobacteria play an important role in gut health, vaginal bifidobacteria have not yet been fully characterized. In this study, a baseline description of the "healthy" vaginal microbiome in pregnancy has been established based on cpn60 gene amplicon sequencing. The vaginal microbiota of pregnant women relative to non-pregnant women had lower richness and diversity, higher Lactobacillus abundance and lower Mollicutes/Ureaplasma prevalence. This gives a better understanding of the vaginal microbiome in healthy pregnancies and provides a control group for a subsequent comparison to women who experienced preterm birth. An association between Mollicutes and preterm was confirmed, and further suggested that a more rich and diverse microbiome is associated with prematurity. To better understand the relationship between reproductive outcomes and microbiota, an improved definition of the healthy microbiome is also needed, which should include evaluation of "atypical" microbiomes, such as Bifidobacterium-dominated. Phenotypic characterization of vaginal bifidobacteria indicated that they have health promoting characteristics similar to beneficial vaginal lactobacilli. Considering the importance of bifidobacteria as one of the primary colonizers of the neonatal gut, the genomes of vaginal and gut isolates of Bifidobacterium breve and Bifidobacterium longum were compared. Results indicated that vaginal and gut microbiomes are colonized by a shared community of Bifidobacterium, which may be transferred from mother to infant. Taken together, the results presented in this thesis provide a better understanding of the vaginal microbiome of pregnant women with low and high risk for preterm birth. It also improves the understanding of a healthy microbiome by phenotypically characterizing vaginal bifidobacteria, and contributes to elucidate aspects of bifidobacteria ecology by comparing the genomes of vaginal and gut bifidobacteria.