VCU news

By Sathya Achia Abraham

Humans are home to millions of microbes - and that’s not a bad thing. In fact, it is now generally accepted that communities of microbes – commonly called microbiomes – profoundly impact health via effects on the local microenvironment.

Gaining a more complete picture of the community of microorganisms inhabiting each of us can tell us a little about our own health and susceptibility to various diseases.

Enter a unique, cross-disciplinary cluster of researchers, nearly 40-people strong, from across Virginia Commonwealth University’s campuses working on a four-year study of how microorganisms found in the vagina influence health and disease in women.

The team, which includes women’s health experts, physicians, pathogenic microbiologists, geneticists, epidemiologists, biostaticians and systematic biologists, will determine the role of genetics in the composition of vaginal microorganisms, and how changes in the vaginal microbiome are associated with disease or common physiological states such as pregnancy and menopause, or abnormal conditions such as pre-term labor and diabetes.

One unique component to the project is that the group will be using twin research to examine the vaginal microbiome. Currently, the team is recruiting participants for the study through the VCU Mid-Atlantic Twin Registry and clinics at the VCU Medical Center. Read about VCU’s twin research here.

“Our project focuses on the vaginal microbiome because of our expertise in urogenital microbiology, women’s health and twin studies,” said Gregory Buck, Ph.D., director of the VCU Center for the Study of Biological Complexity and the principal investigator for the microbiome project at VCU. In addition to the vaginal microbiome being studied at VCU, other institutions are studying and collecting data on the microbiota inhabiting the gastrointestinal tract, oral cavity, naso-pharyngeal tract and skin as part of the National Institutes of Health Human Microbiome Project.

“VCU is extremely well placed to explore the impact of the vaginal microbiome on women’s health issues and to further explore the role of human genetics on the composition of the vaginal microbiome,” Buck said.

Once researchers have gathered samples from women participating in the study, the DNA of the microorganisms will be analyzed using VCU’s advanced “next generation sequencing” capabilities – powerful technologies used to sequence genomes of humans, microorganisms and other species of interest to scientists. Ultimately, the information will help the team identify associations among these microbiome profiles and vaginal disorders.

A Roadmap Project

The VCU project is one of eight across the country that were launched in 2009 as part of the NIH Human Microbiome Project, a $157 million, five-year effort started in 2008 as part of the NIH Common Fund’s Roadmap for Medical Research.

The project will produce a resource for researchers seeking to understand the function of the human microbiome in health and disease and to provide strategies to develop new therapies that manipulate the human microbiome to improve health.

Researchers will pool the data collected from their investigations into a central database, where specialized analysis can take place. The purpose of the Human Microbiome Project is to advance the rate of discovery and translate the findings for use in new strategies to prevent, diagnose or treat disease and to get them to health care providers and the bedsides of patients.

A unique microbiome

The vagina, like many other body sites, is colonized by complex communities of protective bacteria and other microorganisms. Unhealthy and pathological conditions such as bacterial vaginosis and sexually transmitted disease, and viral infections such as HPV or even HIV-1, are known to impact the vaginal microbiome. Normal events such as menstruation, menopause and pregnancy are also known to change the microbiome.

For example, microflora associated with bacterial vaginosis is believed to contribute to the risk of miscarriage in the second trimester or preterm birth. And alterations that occur in pregnancy or menopause can change the makeup of normal vaginal microflora, which may increase the risk for infection, disease or transmission of a virus, such as HIV-1.

Changes in the vaginal microflora are thought to have an effect on disease progression and severity and may impact treatment outcomes. Despite its perceived importance to women’s health and disease, the microbiome of the vagina in pathological conditions has neither been well characterized nor quantified.

“If certain genetic characteristics of the woman are associated with vaginal disease, or with susceptibility to vaginal disease, it may be possible to affect the progression of those diseases. Knowing associations between microbiome profiles and disease would also permit us to carefully monitor susceptible women and prevent the development of pathological conditions,” said Buck, who is a professor of microbiology and immunology in the VCU School of Medicine

Putting together the pieces

According to Buck, “next generation” sequencing includes several new technologies that have significantly enhanced the throughput /output of DNA Sequencers and will help tremendously in moving this research forward.

“Next generation sequencers have dramatically increased the efficiency and decreased the overall cost of DNA sequencing to the extent that large genome projects  that were previously the domain of massive genome centers can now be performed with a single instrument in a single laboratory,” said Buck.

Co-principal investigators on the grant are Jerome F. Strauss III, M.D., Ph.D., dean of the VCU School of Medicine; Cynthia Cornelissen, Ph.D., from the Department of Microbiology and Immunology; and Lindon Eaves, Ph.D., from the Department of Human and Molecular Genetics.