title: Pathogenesis of and unifying hypothesis for idiopathic pouchitis.
abstract: Ileal pouch-anal anastomosis is the procedure of choice in the surgical management of refractory ulcerative colitis. Pouchitis affects up to 60% of patients following ileal pouch-anal anastomosis for ulcerative colitis. It overlaps significantly with ulcerative colitis such that improvements in our understanding of one will impact considerably on the other. The symptoms are distressing and impinge significantly on patients' quality of life. Despite 30 years of scientific and clinical investigation, the pathogenesis of pouchitis is unknown; however, recent advances in molecular and cell biology make a synergistic hypothesis possible. This hypothesis links interaction between epithelial metaplasia, changes in luminal bacteria (in particular sulfate-reducing bacteria), and altered mucosal immunity. Specifically, colonic metaplasia supports colonization by sulfate-reducing bacteria that produce hydrogen sulfide. This causes mucosal depletion and subsequent inflammation. Although in most cases antibiotics lead to bacterial clearance and symptom resolution, immunogenetic subpopulations can develop a chronic refractory variant of pouchitis. The aims of this paper are to discuss proposed pathogenic mechanisms and to describe a novel mechanism that combines many hypotheses and explains several aspects of pouchitis. The implications for the management of both pouchitis and ulcerative colitis are discussed.
authors.affiliation: School of Medicine and Medical Sciences University College Dublin, St Vincent's University Hospital, Dublin, Ireland. calvincoffey@hotmail.com
authors.forename: J Calvin
authors.initials: JC
authors.lastname: Coffey
authors.forename: Fiachra
authors.initials: F
authors.lastname: Rowan
authors.forename: John
authors.initials: J
authors.lastname: Burke
authors.forename: Neil G
authors.initials: NG
authors.lastname: Dochery
authors.forename: Neil
authors.initials: N
authors.lastname: Dochery
authors.forename: William O
authors.initials: WO
authors.lastname: Kirwan
authors.forename: P Ronan
authors.initials: PR
authors.lastname: O'Connell
mesh_terms: D001003:Anal Canal / Q000382:microbiology / Q000473:pathology / Q000601:surgery; D000714:Anastomosis, Surgical / Q000379:methods; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001419:Bacteria / Q000254:growth & development*; D003093:Colitis, Ulcerative / Q000601:surgery; D039021:Colonic Pouches / Q000382:microbiology / Q000473:pathology; D003937:Diagnosis, Differential; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology*; D008679:Metaplasia / Q000473:pathology; D011183:Postoperative Complications; D019449:Pouchitis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology
chemical_list: D000900:Anti-Bacterial Agents