Scientific Abstract

Proposal No. IBD-0014
Principal Investigator:  Stephen J. Danon, Ph.D.
Applicant Organization:  University of New South Wales (Sydney, Australia)
Project Title:  Immunization with mucous-associated bacteria of the intestine, including helicobacter species, as a novel approach to the prevention and amelioration of inflammatory bowel disease
Award Period:  August 1, 2002 - July 31, 2003

The role of bacteria in inflammatory bowel disease (IBD) has been suspected for many years, yet no specific microorganism(s) have been conclusively associated with this condition.  Recent animal studies have indicated that novel mucous-associated spiral bacteria could play a role in the initiation and thus cause the inflammation in IBD.  These bacteria, which until recently have been largely ignored, live in the mucous layer close to the gut surface of both humans and animals.  Genetic analysis of these mucous-associated bacteria has indicated that many belong to a group called the Helicobacters.

Exciting preliminary experiments from our laboratory have shown that therapeutic immunization with bacterial antigens, derived from sonicated preparations of these mucous-associated bacteria, plus a mucosal adjuvant, can eliminate the IBD in an IL-10^-/- transgenic animal model of IBD.  This proposal is designed to extend our initial observations by repeating these studies using antigens obtained from mixtures of mucous-associated bacteria as well as investigating the effectiveness of single bacterial preparations of Helicobacter spp and other mucous-associated bacteria.

The purpose of our study is to gain an understanding of the processes involved in disease progression and prevention.  This will be achieved by:  i) identifying possible initiators of the disease by analyzing mucous- associated bacteria of the lower bowel before and after immunization and ii) investigating the immunological processes that occur (in particular, the expression of various cytokines) prior to and after immunization.  The overall goal of this project is to better understand the role of mucous-associated bacteria in gastrointestinal inflammation using a mouse model of IBD so that this information can ultimately be used to devise successful therapies to prevent and cure human inflammatory bowel disease.