Review article: the pathogenesis of pouchitis

Abstract

SUMMARY Background A total proctocolectomy followed by ileal pouch-anal anastomosis (IPAA) is a potentially curative surgery for ulcerative colitis (UC) or familial adenomatous polyposis (FAP). About 5-35% of UC patients and 0-11% of FAP patients develop subsequent inflammation of the ileal pouch termed pouchitis. Aim The aim of this review was to provide a comprehensive analysis of the research studying the possible pathogenesis of pouchitis. The goals were to identify promising areas of investigation, to help focus clinicians, researchers, and patients on how to better understand and then potentially manage ileal pouchitis, and to provide avenues for future research investigations. Methods This review examined manuscripts from 1981 through 2015 that discussed and/or proposed hypotheses with supportive evidence for the potential underlying pathogenic mechanism for pouchitis. Results The pathogenesis of pouchitis is not definitively understood, but various hypotheses have been proposed, including: 1) recurrence of UC, 2) dysbiosis of the ileal pouch microbiota, 3) deprivation of nutritional short chain fatty acids, 4) mucosal ischemia and oxygen free radical injury, 5) host genetic susceptibility, and 6) immune dysregulation. However, none of these alone are able to fully explain pouchitis pathogenesis. Conclusions Pouchitis, similar to IBD, is a complex disorder that is not caused by any one single factor. More likely, pouchitis occurs through a combination of both dysregulated host inflammatory mechanisms and interaction with luminal microbiota.

Systematic review: ileoanal pouch microbiota in health and disease

“…A significant limitation of studies in ileoanal pouch microbiota is accounting for confounders that influence the gut microbiota such as medications, diet, smoking and age. It has been suggested that pouchitis is not caused by a single factor and the microbiota is just one of the factors that contribute to inflammation. This is obviously an issue with any disease and is something that cannot be avoided but should be considered when analysing the literature.…”

“…The role of the microbiota has been suggested to contribute to the pathogenesis of pouchitis, although its exact aetiology remains unclear. Novel laboratory techniques including next generation sequencing have transformed our understanding of the gut microbiota although the exact bacterial taxonomical shifts in the ileoanal pouch have been difficult to interpret due to the heterogeneity in study designs, sampling techniques and analysis.…”

The outcome of ulcerative colitis patients undergoing pouch surgery is determined by pre‐surgical factors

“…Most importantly, given that pouch surgery is inevitable in many cases, post‐operative preventive measures could be suggested to patients with the aforementioned predictive characteristics such as refractory indications. As the chronic forms of pouchitis are complex and difficult to treat these patients with higher risk to develop pouchitis may be considered for early preventive measures such as early use of probiotics or antibiotic or in specific cases immunomodulatory/biological therapy.…”

“…Since UC is primarily restricted to the large bowel, it was expected that pouch surgery will enable eradication of diseased mucosa and a cure for UC. However, following the surgery, up to 60% of patients will develop inflammation of the pouch (“pouchitis”), and up to 30% may develop the more complicated phenotypes of chronic pouchitis (CP) or Crohn's‐like disease of the pouch (CLDP) . These conditions negatively impact patients' quality of life and often require long‐term medical therapy, mostly difficult and empirical .…”

Recombinant Probiotics and Microbiota Modulation as a Good Therapy for Diseases Related to the GIT

“…The reported incidence of pouchitis is variable, generally because of the diagnostic criteria that have been used to define this syndrome [38,39]. In addition, although its pathogenesis is uncertain, the main hypothesis for the mechanism by which the disease occurs is the break in the mucosal barrier generated by dysbiotic microbiome in susceptible patients, generating an unusual mucosal immune activation [40]; still the disease typically responds to antibiotics.…”