Our understanding of this relationship between the vaginal tract microbiome and human disease is now poised to change - A report by the National Research Council supporting a Global Metagenomics Initiative states that metagenomics “presents the greatest opportunity to revolutionize understanding of the microbial world” [55
]. The term metagenomics was first used in the late 1990s, and was defined as the genomic analysis of microorganisms by direct extraction and cloning of DNA from an assemblage of microorganisms without the necessity for culturing. The availability of “next generation” sequencing technologies have made it such that a cloning step is no longer essential for metagenomic projects and one can now rapidly, and with unprecedented depth, define the total microbial community or microbiome (the number and relative abundance of microbial species present), and their metagenomes (the microbial functional content). The application of these technological advances will provide an understanding of the overall composition and physiology of the vaginal microbiome, and will provide objective analytical and biomolecular tools to assess and improve women’s health. Ultimately, we believe this work will revolutionize the diagnosis and treatment of vaginal diseases, including pre-term birth, and thus will have a significant overall impact on women’s health.
Metagenomics holds significant promise for increasing our understanding of many microbial diseases associated with the human body, especially those considered to be polymicrobial in origin. Indeed, the landscape of microbial ecology as it relates to human disease has been altered forever by the advent of metagenomics and has led to the National Institutes of Health’s (NIH) Human Microbiome Project (HMP). The HMP has the overall goal of demonstrating the role the human microbiome plays in human health and disease by promoting a combined assessment of microbial population structure with an assessment of community function. Ultimately, the goal of the HMP is to provide a reference database of genome and metagenome sequences and an estimation of the microbial community structure at various body sites in healthy individuals. This will establish if there is a “core microbiome” at each body site indicative of a healthy status, and will provide the baseline community structure databases that will enable application of Koch’s Postulates to previously intractable human diseases. That is, the correlation of microbial community structure or microbiome, rather than a single microorganism, to healthy and diseased states.
Initial studies are beginning to define the microbial, metabolic and immunologic components of the vaginal ecosystem and the effects of demographic variables on these parameters. Despite this progress, several large gaps exist in our knowledge about the vaginal ecosystem including the role of factors such as host genetics[56
], environmental exposure[58
] and health status[59
] on the abundance and interactions of individual microbial species, related taxa, and groups of distantly related microorganisms. For example, it is commonly believed that the vaginal microbiome is an indicator of health, whereas women with an altered composition of vaginal microbes are more likely to exhibit symptomatic infections and increased risk of sexually acquired diseases or pregnancy complications [60
]. Culture-dependent identification of vaginal microbes has provided only an incomplete understanding of the vaginal microbiome [16
], and a profound knowledge gap remains regarding the linkage between the vaginal microbiome and pre-term birth. For example, until recently there was a common belief that the vaginal microbiome include only a few species, predominantly from the genus Lactobacillus
, the so-called “good” bacteria. Vaginal disease has been simplistically modeled to result from a decrease in the percentage of lactobacilli and concomitant overgrowth by other bacterial species such as Gardnerella vaginalis
. However, it is clear from genomic analysis of G. vaginalis[65
and Lacobacillus iners
that it is the virulence potential, both genomic and metabolic, of the strain of that is crucial, as BV isolates have numerous gene set and metabolic potentials that increase their pathogenic potential over non-BV isolates. Thus, the mere presence or absence of these bacterial species is not indicative of the disease state, but more importantly it is the metabolic potential harbored in these bacterial species that defines a commensal from a pathogenic strain.
Metagenomics and computational biology approaches are providing the biological, technological, and reference genome resources that we believe will enable significant advances in our understanding of health and disease and address the issues of metabolic potentials, not bacterial strains as indicators or mediators of disease. Whenever these techniques have been applied, whether to study environmental sites or commensal communities of humans and animals, the apparent diversity of microbes has been astounding. From the few such studies that have been conducted to survey the human vaginal microbiome, the number of species present has exceeded, by orders of magnitude, the diversity determined using classic culture-based methods [36
]. Not only is there is an incredible diversity of microorganisms present within individual women, but the vaginal populations among different healthy women are highly varied [36
]. Our recently published studies which showed that the vaginal microbiome is heterogeneous within an individual support this observation [70
], but this is just the beginning. Although two recent studies. have examined racial differences and host genotype in vaginal microbial communities [69
], the impact of other variables that might contribute to microbiome composition and diversity such as age, race/ethnicity, other demographics, medications, medical conditions, sexual practices, or hormone status (normal menstrual cycle, birth control pills, menopause, pregnancy) is currently unknown. There is thus a critical need for additional high-throughput genomics based approaches to characterize the vaginal microbiome.