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.

Cyclosporine A Regulates Pro-Inflammatory Cytokine Production in Ulcerative Colitis

“…Although the aetiology and pathogenesis of IBD are far from being understood in detail, there is the general consensus that defects in the maintenance of immune responses, diminished barrier integrity, luminal antigens and alterations in pattern recognition receptors expressed in epithelial cells exacerbate the pathogenesis of IBD (Günther et al 2011;Mandai et al 2013;Vivinus-Nebot et al 2014;Zheng et al 2013). Another putative form of IBD is pouchitis, which is mostly developed by UC patients after ileal pouch-anal anastomosis (Coffey et al 2009;Shen 2013). It has been shown before that IBD patients are characterized by altered profiles of pro-and anti-inflammatory cytokines in lamina propria CD4…”

FK506-Binding Protein 5 mRNA Levels in Ileal Mucosa Are Associated with Pouchitis in Patients with Ulcerative Colitis

“…The incidence of pouchitis has been reported to be 40-70 % in ulcerative colitis patients who receive IPAA [15,16]. Although the etiology of pouchitis remains unclear, several studies have reported an increased incidence of pouchitis in patients with extraintestinal manifestations [17][18][19][20][21], especially for primary sclerosing cholangitis [22][23][24], shorter disease duration [15], extent of disease [15,21], younger age [21], more severe preoperative clinical course [2], and steroid dependency [2].…”

The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis

“…2,4 The pathogenesis of pouchitis is still poorly understood and may result from several causes such as ischaemia, 5 altered mucosal metabolism, 4 bile acid cytotoxicity, 6,7 recurrence of UC and genetic susceptibility. 8 Allelic variations in genes encoding for IL-1 receptor antagonist (IL-1 RN), TNF and NOD2 have all been associated with an increased risk of developing pouchitis in UC patients. [9][10][11] These factors are in various ways related to regulation of epithelial physiology and defence, thus suggesting a pathophysiological role for mucosal barrier function in pouchitis.…”