Lay Summary

Proposal No. IBD-0240R2
Principal Investigator: Paris Tekkis, M.D. 
Applicant Organization: Imperial College of Science, Technology and Medicine (London, England)
Project Title: Investigation of the bacterial pathogenesis of inflammation of the ileal reservoir following restorative proctocolectomy for ulcerative colitis and familial adenomatous polyposis 
Award Period: April 1, 2009 – September 30, 2010

Almost one third of patients with ulcerative colitis will require surgery to remove the diseased large bowel (colon and rectum) due to the failure of drug treatment or the development of pre-cancerous changes. Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is accepted as the operation of choice. Unfortunately up to half of ulcerative colitis patients will develop inflammation in the ileal pouch, so called ‘pouchitis’, following surgery. This operation is also performed in some patients with the pre-cancerous disease familial adenomatous polyposis but a much smaller percentage (about 5%) of these patients develops pouchitis. Because IPAA is performed for both ulcerative colitis and familial adenomatous polyposis it provides an excellent model to better understand the causation of inflammatory bowel disease (IBD).

Pouchitis is an inflammatory condition which affects the lining (mucous membrane) of the pouch causing symptoms similar to that of ulcerative colitis such as increased stool frequency, urgency, bleeding and stomach cramps. The cause of this condition is unknown, however most doctors and scientists agree that this disease (as well as other forms of IBD) is driven by bacteria, probably either through an imbalance between disease protective and disease predisposing bacteria or simply by the presence of abnormal harmful bacteria.

There are approximately 600 bacterial species associated with the human gut. The identification of these has been difficult because many of them cannot be cultured or identified by conventional techniques. We will use a powerful modern molecular biology technique, 16S ribosomal RNA sequencing. This technique uses polymerase chain reaction (PCR) to amplify copies of the gene which encodes the 16S subunit of bacterial ribosomes. This gene is present in all but unique in its DNA sequence to individual bacterial species. The resultant copies of the 16S gene are then sequenced, enabling the isolated bacterial species to be identified from their unique genetic code.

We will identify and compare the bacteria present in the pouches of patients with active pouchits and non-pouchitis in patients having IPAA for ulcerative colitis and familial adenomatous polyposis.

We will also investigate for the presence of molecules which bind cells together by staining sections of pieces of tissue from patients with pouchitis, FAP and control patients and potentially correlate this with the changes in the gut bacterial population. The results of this study should lead to significant improvements in the understanding of both pouchitis and IBD in general. Identification of individual bacterial species which predispose individuals to or cause pouchitis should allow the development of specific antibiotic or probiotic regimes to treat or prevent episodes of pouchitis and possibly ulcerative colitis and Crohn’s disease.