Urologic Diseases Research Updates
Fall 2009

NIH Funds DNA Sequencing Centers and Pilot Projects to Study Influence of Microorganisms on Human Health and Disease

Pilot Projects Will Investigate Relationships to Urologic Diseases

While a great deal is known about disease-causing pathogens, relatively little is known about the seemingly innocuous microorganisms living in and on the human body. Called the microbiome, this microbial community outnumbers the body’s own cells by a factor of 10. Mounting evidence suggests the microbiome plays a bigger role in human health and disease than previously thought.

Human Microbiome Sequencing Centers

In June, the National Institutes of Health (NIH) awarded additional funds to the Human Microbiome Project’s (HMP’s) ambitious 5-year effort to sequence the DNA of about 400 humanassociated microorganisms. These microbial “genomes” will be added to the 500 or so that have already been or are in the process of being sequenced.

The net result will be a reference database that researchers can use to study associations between human-associated microorganisms and diseases, including urologic conditions.

“This effort will accelerate our understanding of how our bodies and microorganisms interact to influence health and disease,” said Raynard S. Kington, M.D., Ph.D., NIH deputy director.

The HMP is sequencing microbial DNA collected from five areas of the body: the digestive tract, the mouth, the skin, the nose, and the vagina. HMP-funded sequencing centers include

• The Human Genome Sequencing Center, Baylor College of Medicine, Houston
• The Washington University Genome Sequencing Center, Washington University School of Medicine, St. Louis
• The J. Craig Venter Institute, Rockville, MD

The Broad Institute of the Massachusetts Institute of Technology and Harvard, which previously participated in the project, is also expected to participate in this phase of the project.

Pilot Projects

The HMP also received funding for several pilot projects to compare the microbiomes of healthy people with those of people with specific diseases affecting the mouth, nose, skin, blood, digestive tract, vagina, and male urethra.

“Examining differences between the microbiomes of healthy people and people suffering from disease promises to change how we diagnose, treat, and ultimately prevent many health conditions,” said Kington.

Each pilot project will be reviewed after 1 year to evaluate its progress and its ability to demonstrate a definable relationship between a body site microbiome and disease.

Three pilot projects are relevant to urologic diseases.

Bacterial Vaginosis

Two pilot projects will examine the relationship between the vaginal microbiome and bacterial vaginosis—a common condition in which certain bacteria in the vagina outgrow others. Bacterial vaginosis can cause great discomfort and has been shown to be associated with increased risks of sexually transmitted disease, premature birth, and other conditions.

Gregory A. Buck, Ph.D., of Virginia Commonwealth University, Richmond, and colleagues are examining factors that may influence the composition of the vaginal microbiome, such as the woman’s genetics, pregnancy, menopause, infection, and other environmental factors. Using ”metagenomic“ techniques that characterize microbial communities according to their DNA composition, Buck and colleagues will examine and compare vaginal microbiomes of identical and fraternal twins, individuals of various ethnicity, and women with infections or other pathologies.

“There is a lot we still do not know about the human microbiome. Studying microbial populations of the vagina will allow us to better understand women’s health issues, particularly those related to the urogenital tract, and lead to important therapies or interventions to keep women healthy,” said Buck.

Jacques Ravel, Ph.D., of the Institute for Genome Sciences, part of the University of Maryland School of Medicine, and Larry Forney, Ph.D., of the University of Idaho have received HMP funds to characterize the daily variations of the vaginal microbiome during a 10-week period. Understanding how these variations correlate with bacterial vaginosis are elemental to understanding the interplay among vaginal microorganisms, the human host, and the environment as they relate to health and disease, according to Ravel. By examining daily samples from 250 women, Ravel, Forney, and colleagues will develop models of the molecular and environmental events that maintain health and lead to bacterial vaginosis. Information from these studies, said Ravel, is essential to developing better and more personalized treatments.

Male Urethra

J. Dennis Fortenberry, M.D., of the Indiana University School of Medicine, Indianapolis, and colleagues were funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to characterize the microbiome of the adolescent male urethra, which may play a role in sexually transmitted infection (STI).

By evaluating monthly urine samples collected from an ethnically diverse population of males, 14 to 17 years old at study enrollment, the research team will look for changes in the urethral microbiome over time and their correlation with development, sexual activity, and STI. The study will provide participants with cell phones to report key events, including participation in specific sexual acts, antibiotic use, condom failure, and genital symptoms.

NIH Roadmap

The HMP is part of the NIH Roadmap for Medical Research, which, through a series of initiatives, addresses major opportunities and gaps in biomedical research that no single NIH Institute can tackle alone. The HMP is managed by several Institutes, including the NIDDK.

For more information about the HMP, visit www.hmpdacc.org and www.nihroadmap.nih.gov/hmp.

The NIDDK has patient information about urologic diseases. Fact sheets and easy-to-read booklets are available at www.urologic.niddk.nih.gov.

NIH Publication No. 10–5743
December 2009

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