WASHINGTON, D.C.—Aimed at unlocking the mystery of the human microbiome and understanding how and why the alteration of normal microbes in the body promotes disease, the U.S. National Institutes of Health (NIH) has earmarked $22.1 million for 2013, 2014 and 2015 to fund three innovative research projects related to the relationship of bacteria and infectious diseases to diabetes, to Crohn's disease and colitis and to reproductive health issues—specifically, how pregnant mothers pass along these diseases to their newborns.
These projects constitute the second phase of the Human Microbiome Project (HMP). The first phase began in 2007, and focused on the composition and genetic potential of the microbial communities on the body and how these differ in health and disease. The second phase focuses on measuring the biochemical activities that hold the key to how microbes influence the physiology of the human host. "People are host to trillions of microbes living on their skin and in the gut, vagina, mouth, nose, lungs and penis," the NIH stated in a Sept. 9 press release. "For the most part, we peacefully co-exist with these microbes. But sometimes, some of these microorganisms such as bacteria can trigger responses that may cause people to develop a disease."
The NIH has set aside $2.5 million for fiscal year 2013 to fund the first joint project by research teams at Stanford University and Washington University in St. Louis to examine the microbes in the gut and nose, and to determine how alteration in certain microorganisms (for example, during viral infections) may trigger the development of diseases such as diabetes. Researchers will use several 'omics approaches, including genomics, transcriptomics and proteomics to follow the dynamic changes in the microbiome and in the host over time.
The NIH has also earmarked $2.5 million to fund the second joint project, conducted by research teams at the Broad Institute and the Harvard School of Public Health in Cambridge, Mass. Also using 'omics technologies, investigators will assess the populations and physiological activities of gut microbes in people with Crohn's disease and ulcerative colitis—two chronic inflammatory bowel diseases (IBD), in order to advance knowledge of the disease mechanisms. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) will manage these grants.
The NIH has also agreed to give $2.5 million to a third project. Conducted by a research team at Virginia Commonwealth University in Richmond, investigators will also use genomics and other 'omics technologies to study bacteria that live in the vagina and assess the roles these bacteria play in health and disease in pregnant women as well as in their babies, particularly for preterm birth. The Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) will manage this grant. The awards are primarily funded through the NIH Common Fund, which supports high-impact pioneering research across the agency. The NIH has not yet decided on the funding amounts for the three projects in 2014 and 2015.
"This is a new area of research for the NIH and NICHD," says John V. Ilekis, health science administrator at NICHD's Pregnancy and Perinatology Branch. "It has broad implications, including reproductive health, pregnancy and overall pediatric health." Initially, researchers will conduct a study of 2,000 women and their babies at Virginia Commonwealth University Health Center Women's Clinics and Seattle Children's Hospital. The long-term objective is to promote studies of women's health during pregnancy, and specifically to assess the role of the microbiome as a potential cause of preterm birth, according to Gregory A. Buck, director of the Center for the Study of Biological Complexity.
On the diabetes front, Dr. Salvatore Sechi, NIDDK senior advisor for proteomics and systems biology, says the diabetes project got off the ground after Dr. Michael Snyder at Stanford University and Dr. George Weinstock at Washington University submitted a proposal for establishing a center for the longitudinal analysis of the microbiome and the human host during healthy and disease states using several 'omics technologies such as proteomics and genomics. The disease focus is on subjects at risk of developing type 2 diabetes.
"Dr. Snyder has already published data suggesting that a viral infection with human respiratory syncytial virus—a common virus that causes respiratory tract infections—can induce type 2 diabetes," Sechi says.
Type 2 diabetes "is a complex and heterogeneous disease that can lead to hyperglycemia," he notes. "Many factors have been shown to be important in the pathophysiology of this disease. These include genetic predisposition, obesity and lifestyle."
However, this study "may help understand the mechanism by which a viral infection, or more generally, the microbiome, can influence glucose homeostasis to the point of making a subject diabetic," Sechi adds. "In its beginning, this study will be performed on approximately 40 patients. The extensive 'omics characterization and its present cost limit the present project to what could be called a pilot study from the point of view of population size. However, the very detailed characterization of the microbiome and host could lead to major changes in the way we think about type 2 diabetes."
In preliminary data published by Dr. Snyder's group, "a lifestyle intervention (i.e., change in exercise and diet) was very successful in reverting the subject's glycemic level to normal," Sechi says. "Perhaps if the interventions occur in a very early stage of the disease development, as it occurred in Dr. Snyder's case, we can be more successful in treating the disease with simple lifestyle changes."