Abstract
The vaginal microbiome has a rich history of research dating back more than a century. In recent years modern sequencing technologies have yielded significant new insights that challenge old paradigms and blur the boundaries between health and disease. We currently recognize that multiple kinds of vaginal communities exist in healthy women but are still very much in a natural history phase as we attempt to translate compositional diversity to meaningful differences in ecological function, community stability and, ultimately, women's health. The objective of this dissertation is to begin bridging this gap by incorporating functional characterization and longitudinal sampling into vaginal microbiome studies. In my opening chapter I provide an overview of vaginal microbiome research, recounting significant historical advances and highlighting remaining knowledge gaps. I advocate approaching the vaginal microbiome from an ecological perspective to facilitate our understanding of its role in health and disease.
Next, I describe the development and validation of a microarray designed for rapid functional screening of vaginal microbial communities. I demonstrate efficacy of the microarray on different types of samples and conclude that it could be used to develop informed hypotheses of community function and launch additional detailed studies.
In my third chapter, I characterize longitudinal changes in the vaginal communities of adolescent girls. To date most research has focused exclusively on reproductive age women, so this study addresses an important knowledge gap in understanding the transitions that occur in the microbiome during the formative years of puberty. Importantly I document trends in the rise of lactic acid bacteria, which occurs earlier in puberty than previously thought. I also report observations of Gardnerella vaginalis in several young adolescents, a notable finding considering this species is frequently considered a potential pathogen.
Finally, I explore the genomic diversity of Gardnerella vaginalis, which is increasingly recognized as a common inhabitant of healthy vaginal communities despite its strong association with bacterial vaginosis. Adopting the ecotype concept of intraspecies diversity, I show that G. vaginalis can be separated into multiple phylogenetic clades each in possession of a unique suite of functional traits that may be relevant to both its ecology and postulated virulence.