Metagenomics - HMP Funded Projects

Project Principal Investigator
Obesity Claire M. Fraser Ph.D.
Crohn's Disease Claire M. Fraser Ph.D.
Bacterial Vaginosis Jacques Ravel Ph.D.


Two large studies within IGS are focused on unraveling the contribution of the bacteria that normally inhabit the human gastrointestinal tract and their role in the development of obesity, which has severe metabolic consequences including cardiovascular disease, insulin resistance and Type II diabetes. IGS researchers take a multidisciplinary approach studying changes in the structure and function of gut microbial communities in three sets of Old Order Amish patients from Lancaster Pennsylvania: obese patients, obese patients with metabolic syndrome and non-obese individuals. The Old Order Amish are ideal for genetic studies because they are a genetically closed homogeneous population of Central European ancestry. This work has the potential to provide new insights into the role of gut microbes in obesity and metabolic syndrome, a disease that is responsible for significant morbidity in the adult population, and may ultimately lead to novel approaches for prevention and treatment of this disorder.


Crohn's Disease

Inflammatory bowel diseases (IBD), such as Crohn's disease, are chronic disorders that have severe medical consequences. These diseases may result from an overly aggressive immune response to a subset of bacteria that live in the intestines. While the exact causes of IBD are not known, some studies have suggested that the disorders may be caused by a combination of bacteria and host susceptibility. IGS researchers are working with Drs. Janet Jansson (Lawrence Berkeley National Laboratory) and Robert Hettich (Oak Ridge National Laboratory) to profile Crohn's disease at an unprecedented molecular level by identifying biomarkers (bacterial strains, genes, or proteins) that correlate to disease symptoms. To achieve this goal, the scientists are taking a multidisciplinary approach based on metagenomic and metaproteomic molecular tools to study the composition of the commensal microbiota in identical twins that are either healthy or exhibit Crohn's disease.


Bacterial vaginosis

The vaginal microbiota play an important role in maintaining womens' health. Disruption of the relationship between bacterial communities in the vagina and their hosts can lead to bacterial vaginosis (BV), a condition in which lactic-acid producing bacteria are supplanted by a diverse array of other bacteria. BV has been shown to be a risk factor for pre-term delivery and low infant birth weight, susceptibility to sexually transmitted infections and HIV, and development of pelvic inflammatory disease. National surveys indicate the prevalence of BV among U.S. women is 29%, and yet, despite considerable effort, the exact cause of BV remains unknown. Moreover, there are no broadly effective therapies for the treatment of BV and recurrence is common.

IGS scientists are working with several collaborators, including Co-Principal Investigator Larry Forney, PhD, of the University of Idaho and Co-Principal Investigator Jane Schwebke, M.D. , of the University of Alabama School of Medicine, to try to find out whether the structure and dynamics of vaginal microbial communities are indicators of risk for BV. Samples collected daily from 200 reproductive-age women over two menstrual cycles are the basis for this project to characterize molecular events that take place before, during, and after the remission of BV episodes. Cutting-edge genomic technologies are being used to obtain the data that scientists need to be able to correlate shifts in vaginal microbial community composition and function, changes in metabolism, and other factors with the occurrence of BV.

This project will utilize genomic epidemiology to better define the syndrome itself and to identify patterns that mediate onset and remission of BV. This information will help scientists understand the dynamics of vaginal microbial communities and the causes of BV, both of which are important in developing better diagnostic tools. The research will also enable medical researchers to develop more personalized and effective treatments.