Project Details
Projekt
The role of luminal contents and intestinal alkaline phosphatase in patients with pouchitis after ileal-pouch anal anastomosis for ulcerative colitis
Applicant
Privatdozent Dr. Florian Kühn
Subject Area
General and Visceral Surgery
Term
from 2015 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 298801939
About 30% of patients with ulcerative colitis (UC) will require surgery at some point. Ileal pouch-anal anastomosis (IPAA) has become the standard option for reconstruction after proctocolectomy. The IPAA operation involves the removal of the diseased colon / rectum followed by reconstruction of intestinal continuity, usually with a J-pouch comprised of the termial ileum. An idiopathic primary pouchitis (an inflammation of the new stool reservoir) occurs in up to 50% of patients with UC during the first 10 years after surgery. Pouchitis is clinically marked by abdominal pain and an increase in frequency of bowel movements. Although with proctocolectomy the substrate of UC is removed, pouchitis seems to be associated with the underlying disease since in patients with familial adenomatous polyposis who undergo the same surgical procedure, pouchitis is exceedingly rare. However, the etiology and pathogenesis of pouchitis remain poorly understood; but there is significant clinical evidence that the microbial community plays an important role in its pathogenesis.Toll-like Receptors (TLR) belong to a family of transmembrane receptors that respond to target inflammatory stimuli; they are known to play a principle role in maintaining intestinal barrier integrity and regulating inflammatory cascades within the luminal epithelium. Aberrant modulation of TLR pathways by constituents in the fecal stream is known to play a major role in the pathogenesis of IBD, but there has been little focus on the therapeutic targeting of these luminal factors. We propose to examine for the first time the pro-inflammatory properties of intestinal luminal fluid contents from patients with and without pouchitis after IPAA for UC. In addition, we will test the potential role for the brush border enzyme intestinal alkaline phosphatase (IAP) as a novel therapy to inhibit the inflammatory impact of human enteric contents. We already know that there are decreased IAP levels in IBD and that IAP is exclusively produced in the small bowel. Given that after proctocolectomy with IPAA the substrate of disease should be removed, two major questions remain: (I) will IAP levels be still decreased and (II) is there a connection with pouchitis? If so, we suggest that IAP supplementation could provide a novel therapeutic option for pouchitis.
DFG Programme
Research Fellowships
International Connection
USA
