Inside our Microbiome Initiative—Creating Molecular and Bioinformatic Tools for the Development of IBD Cures
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 people without IBD to identify unique differences in IBD patients, (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, 2 and 3: PI: Jeff Gordon, co-PI: Rob Knight
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.
Phase 2 was instituted in October 2008 and is now completed. This phase 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 builds on the results and collected data of the earlier phases with deep sequencing and new tools for computational analysis. This work has been remarkably successful and was completed in 2012. The new tools generated as part of this research form the basis of phases 3b and 4 (see below).
Phase 4: The Microbiome Consortium
PIS: Dr. Jonathan Braun, UCLA (Lead PI), Dr. Balfour Sartor, Dr. Skip Virgin, Dr. Ramnik Xavier, Dr. Nita Salzman, Dr. Kenneth Simpson, Dr. Luciano Marraffini.
Based on the successes of phases 1-3, the final phase of the microbiome consortium was initiated in January 2011 to identify gut microbioata and their link to IBD flares and remission. The Consortium involves seven multidisciplinary, multi-institutional groups 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.