Microbiome Initiative

Since 1967 the Crohn's & Colitis Foundation has been the leader in inflammatory bowel diseases (IBD) research.  Funding over $150 million to researchers all over the world, the Foundation funds scientists at all phases of their career, supporting investigators at the forefront of IBD research and establishing the Foundation as the pre-eminent IBD research program for non-partisan, peer-reviewed, and results oriented basic and clinical IBD research.

Background

We know that intestinal microbial agents have a key role in causing IBD, but only a limited number of the enormously complex bacteria, viruses and fungi have been identified and their functions are largely unknown.  This project will transform the field by (1) Identifying the components, genes and metabolic products of intestinal bacteria and viruses in normal healthy people, (2) Comparing the bacterial and viral species, genes and metabolic products in IBD patients with those of normals to identify unique differences in IBD patient, (3) Developing bioinformatic techniques to analyze these huge data sets so that all IBD investigators can effectively utilize the results, which will be in public databases accessible to all investigators, and (4) Developing a gene chip that can easily be used by IBD investigators to determine if a functional gene is present in a clinical or experimental sample.

Phase Descriptions and Results

  • Phase 1 of the Gut Microbiome Initiative was initiated on March 2008 and was completed in October 2008.  The goal of Phase I was to develop novel techniques designed to study the microbiomes of both identical and non-identical twins and their mothers, all whom have healthy guts (154 patients total).The study allowed investigators to develop techniques to perform metagenomic (comprehensive analysis of bacterial genes) studies in a small fraction of the time and costs originally projected.

  • Phases 2a & 2b were instituted in October 2008 and are now completed. These phases delved deeper into analyzing the intestinal communities of twin pairs with the communities of their fathers, mothers, and siblings. The gut microbiomes of identical twins were then sequenced in-depth to create “population genomes,” and pilot projects were conducted to explore the patters of gene expression in the gut microbiome. Finally, additional computational tools were developed to analyze massive datasets generated by deep sequencing of the rare biosphere, gene expression profiles, and community structure variation over time.

  • Phase 3a & 3b- Phase 3a builds on the results and collected data of the earlier phases with deep sequencing and new tools for computational analysis. This work, led by Dr. Jeff Gordon, has been remarkably successful and will be completed by end of 2012. Phase 3b will comprehensively compare the fecal microbiome of 30 patients with Crohn’s disease with that of their non-affected sibling and parents daily to coincide the occurrence of flare with any change in the patient’s microbial composition. This study is designed to identify microbial markers that are linked to disease onset or remission.

  • Phase 4 involves 7 multidisciplinary, multi-institutional consortia that include a broad group of IBD investigators who are studying large populations of defined IBD subsets (UC, Crohn’s disease subsets, postoperative recurrence, etc). The investigators share their knowledge, resources and samples to have a better understanding of how the microbiome in different subsets of IBD is similar (or different) and to identify the best microbial biomarkers for IBD. Currently in its second year of funding, the microbiome consortium has already made several key findings which have been published in the form of 4 scientific papers and 15 abstracts.

    • Work from the consortium confirms that the presence of IBD gene variants modifies microbial composition. This is true even in patients with inactive disease and among healthy individuals who carry these genes.

    • Different subsets of IBD have discrete microbial compostions.

    • The consortium has started its first look at viruses and their composition in IBD patients.

Cost

CCFA has raised over $8 million towards the Gut Microbiome Initiative, and seeks continued funding to expand this important project.

For more information about the Microbiome Initiative, click here.

You can support CCFA by clicking here or you can speak with Judith Brown at (646) 943-7441 to learn how to support the Microbiome Initiative.