Lay Summary

Proposal No. IBD-0250

Principal Investigator: Thaddeus S. Stappenbeck, M.D., Ph.D.

Applicant Organization: Washington University (St. Louis, Missouri, U.S.A.)

Project Title: Identification of colitogenic bacteria in an antibiotic-responsive model of fulminant ulcerative colitis

Period of Award: September 1, 2008 – February 28, 2011

 

Humans are susceptible to developing inflammatory bowel disease (IBD) in part because of inherited alterations in specific genes. However, no one of these genetic predispositions alone accounts for IBD. One idea is that multiple alterations in several genes are required. We recently created a new mouse model that suggests this is the case. We combined two genetic alterations that each by themselves create mild disease that takes a long time to develop. However, these two genetic alterations together create severe inflammation throughout the colon of every mouse that contains these two genetic hits.

 

We also found that the inflammation in this model can be abruptly turned off by specific antibiotics and can then in the same mouse be very quickly restarted by re-introduction of colonic microbes from healthy donor mice. This experiment suggests that the microbe or microbes that cause disease in this IBD model are normally present in the colon. The goal of this proposal is to determine what the species of microbes in the mouse colon are that can cause disease. We will attempt to grow these microorganisms in culture. If this proves to be difficult, we have alternative, culture-independent strategies to tackle problem. We will then evaluate patients with pouchitis (a typically antibiotic-sensitive form of IBD) to determine if these are functionally colonized by microbes that can elicit disease.