Image used with permission: The Broad Institute. Illustration by Steven H. Lee
The cells of the human body are outnumbered ten to one by bacteria, but large-scale surveys of the human microbiome were not feasible until the advent of next-generation sequencing. The first stage of the Human Microbiome Project sampled 300 healthy subjects to determine normal microbial composition of healthy Americans (which microbial species were there), their biochemical function (what the microbes were doing), and microbial variation both between individuals and over time. Now that we have determined the healthy human microbiome, the next stage of the Human Microbiome Project is to understand how the microbiome changes in and contributes toward disease.
Inflammatory bowel disease (IBD), which includes both Crohn's Disease (CD) and ulcerative colitis (UC), affects approximately 1.5 million Americans and is one of the most-studied imbalances between microbes and the immune system. Genetic and environmental risk factors exist that are associated with IBD, however they are inadequate to explain the dramatic (more than 400%) increase in IBD over the past 50 years. Rather, a comprehensive body of evidence has linked IBD to the gut microbiota (the bacteria, viruses, archaea, and fungi resident in the gut). In contrast to traditional disease models, no single pathogen seems to cause IBD. Rather, many studies have found an association between IBD and an overall disrupted gut ecology and decrease in diversity.
The IBDMDB will provide an integrated resource for analyzing the gut microbial ecosystem in the context of IBD, improving our ability to understand, diagnose, and treat IBD. It will use several existing, well-described patient cohorts to provide many different types of longitudinal data. By integrating taxonomic, metagenomic, metatranscriptomic, metaproteomic, and metabolic data on the microbiome, we can follow over time which microbial species are present, which biochemical functions they are capable of performing, which functions they are actually performing at any given point in time, and which nutrients are available to the host and microbial community. In addition, in order to better understand how the microbes are interacting with their hosts, the IBDMDB will profile host genetics, epigenetics (DNA modification), and gene expression. A total of 90 subjects will be profiled for one year, and the data will be made publicly available. The IBDMDB project will validate and share both its sample collection protocols and its bioinformatic methods, allowing the scientific community to greatly increase its understanding of interactions between microbes and their hosts in IBD. Please contact us as needed for more information.