Lay Summary

Proposal No. IBD-0027R
Principal Investigator:  Eugene B. Chang, M.D.
Applicant Organization: The University of Chicago (Illinois, U.S.A.)
Project Title:  Identification of probiotic-derived cytoprotective and anti-inflammatory proteins:  novel agents for treatment of inflammatory bowel diseases
Period of Award:  November 1, 2002 - October 31, 2003

Colonic bacteria have an important role in maintaining the health of our gut and in preventing disease by other pathogenic organisms.  However, the composition of intestinal bacteria varies among individuals and can play a major role in the development of experimental colitis and possibly Crohn’s disease.  The unfortunate combination of predisposing genetic background with exposure or colonization by certain inciting commensal bacteria can result in the development of IBD in susceptible individuals.  Because little can be presently done to correct genetic susceptibility, changing the gut flora of IBD patients with probiotic agents is being intensely studied as a therapeutic strategy.  Probiotics are living organisms in food and dietary supplements that have beneficial health effects beyond their inherent nutritive value.  These agents have been shown to be effective in either preventing or mitigating the intestinal mucosal inflammation of colitis.

Our studies will focus on the identification and isolation of the active factor(s) of VSL#3 and other native enteric organisms, as these studies will have immediate relevance to the treatment of IBD.  Several soluble, heat-labile proteins secreted by these organisms have already been partially isolated.  Standard biochemical approaches will be used to identify and further purify the active probiotic factors.

Identification of specific secreted probiotic products represents a major step towards the eventual harvest, concentration, and therapeutic application of these agents.  We believe this approach has a significant advantage over current probiotic practice where efficacy may be limited by unsuccessful bacterial colonization, variations and unregulated composition of formulations, and homeopathic delivery of active agents.  These investigations can therefore lead to the development of new type of therapeutic agents that will benefit patients with IBD.