Scientific Abstract

Proposal No.   IBD-0023
Principal Investigator:  Douglas Morrison, Ph.D.
Applicant Organization:  University of Glasgow (United Kingdom)
Project Title:  Novel strategies for the colonic provision of butyric acid
Period of Award:  June 1, 2003 - March 31, 2006

Inflammatory bowel disease (IBD) is a chronic, relapsing disease involving the whole gut (Crohn’s) or limited to the large bowel (ulcerative colitis (UC)), leading to bloody diarrhea, abdominal pain and weight loss.  The events that trigger the inflammatory response are not clearly defined, but they are multifactorial and may involve genetic, dietary and environmental factors.  Suppressing the inflammatory response may heal the mucosa and control the symptoms of IBD.

Butyric acid is a product of carbohydrate fermentation by the bacterial flora in the large intestine.  It provides the majority of the energy requirements of colonocytes.  It has also been recently shown that butyric acid can suppress pro-inflammatory mediators.  These actions have led to the supposition that increased luminal availability of butyric acid may protect against and ameliorate IBD.  However, there are conflicting data on the capacity of colonocytes to utilize butyric acid in IBD.  It remains unclear whether IBD is a malfunction in the primary oxidation mechanism or the result of an inadequate supply of butyric acid from bacterial fermentation.

Several strategies have been employed to increase the luminal availability of butyric acid, but their efficacy has been difficult to assess because there are no available methods to measure butyric acid production in vivo.  Therapeutic provision of butyric acid may have an advantage over conventional therapy because butyric acid is a natural product of colonic fermentation and may therefore provide a treatment that is free from side effects.  Moreover, because butyric acid is the primary fuel for colonocytes and an important signaling molecule, therapies that increase the luminal provision may be an important adjuvant to current and emerging treatments for IBD.

Ways of reproducibly delivering butyric acid to the colon are therefore necessary to test its potential as a therapeutic agent in colorectal disease.  We have developed a novel carrier system to deliver butyric acid to the colon that can be taken orally.  Using stable isotope methods, we will measure the amount of butyric acid that is delivered to the large intestine by this system.  This innovative delivery system, which will be capable of supplying and sustaining known amounts of butyric acid in the colon, will allow clinical trials to be conducted to evaluate the efficacy of butyric acid as a therapeutic agent in IBD.