Data repository

The VMRC is using multi-omics approaches, including 16S rRNA gene sequencing compositional survey, metagenomics, metatranscriptomics, metabolomics, culturomics and immunological evaluation of biological samples collected in pregnant and non-pregnant women who experienced microbiome stability and instability. The data will be freely available to the scientific community through this portal. Analyses will employ integrative modeling strategy to better understand the underlying factor and combination of factors that drive community stability and instability.

Problem statement

Microbial communities in the human vagina exhibit symbiotic relationships with the host and play critical roles in maintaining health and preventing disease. These roles include protection against colonization and disease by pathogens and regulation of local immune responses. Several different kinds of vaginal communities occur in reproductive age women and are associated with health; the majority of these community types are dominated by one of several Lactobacillus species (L. iners, L. crispatus, L. gasseri, and L. jensenii), each of which is believed to provide key ecosystem services. Lactic acid production is a particularly important trait of these species, one consequence of which is acidification of the vaginal habitat. Lactobacillus species and strains vary in their production of lactic acid, as well as in their associations with vaginal health- and disease-associated states. Other members of these Lactobacillus-dominated communities presumably play supporting and/or modulating roles in community-associated beneficial services. In contrast, a distinct set of vaginal communities is characterized by low-Lactobacillus abundance and high species diversity, including the presence of Gardnerella vaginalis and other strict and facultative anaerobic bacteria; these low-Lactobacillus, high diversity communities are sometimes associated with adverse health states, such as bacterial vaginosis, and increased risks of HIV acquisition, sexually-transmitted infections, vaginal candidiasis, and premature birth. These adverse states are believed to be associated with either overt or subclinical local inflammation, suggesting a potentially important role for host responses in these outcomes.

Vaginal community composition is temporally dynamic as the community composition shifts from one type to another (e.g., Lactobacillus-dominant versus Lactobacillus-impoverished), but this dynamic behavior differs among individual women. Importantly, the relationships between community composition and function (ecosystem services), potential functional changes during these periods of shift, and the drivers responsible for these shifts are all poorly understood. Some have hypothesized that the frequency and the duration of shifts to a low-Lactobacillus state correlate with risk of adverse health and that combinations of microbial species and strains (bacterial, viral and fungal), genes and/or gene expression, metabolites and host immune factors in the vagina may explain the frequency of changes and duration of the alternative community states. As in any robust ecosystem, the interactions among these features and factors are likely to play fundamental roles in determining stability and function. Given variation in composition, communities presumably will also differ in the number and kinds of interactions among community members and the host. Work on this critical ecosystem so far has focused on individual features and failed to take a holistic, ‘systems’ approach with measurements of many features, both microbial and host-based, and an integrative strategy. As a result, we have an insufficient understanding about the relationships among community species and strain composition, ecological functions, stability of the vaginal microbiota, and risk for disease or adverse gestational outcome.

Resources

Consortium Members

Dr. Jacques Ravel
Institute for Genome Sciences
University of Maryland School of Medicine

Dr. David Relman
Stanford University

Dr. Doug Kwon
Harvard University

Dr. Emily Balskus
Harvard University

Dr. Don Ingber
Wyss Institute
Harvard University

Funding

Bill & Melinda Gates Foundation

This resource is being hosted and maintained at:
Institute for Genome Sciences
University of Maryland School of Medicine
670 W. Baltimore Street
Baltimore, MD 21201
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