The Interaction Between Intestinal Microbiota, Innate Defense and Epithelial Integrity in the Development of Pouchitis

The Interaction Between the Intestinal Microbiota, Innate Defense and Epithelial Integrity in the Development of Pouchitis: a Multifactorial Approach

Pouchitis is a common complication following proctocolectomy with ileal pouch anal anastomosis (IPAA) in patients with ulcerative colitis (UC). It affects the quality of life and can become a chronic problem. The aetiology of pouchitis is not completely understood. A crucial role of the intestinal microbiota has been suggested, but no causative agent has been identified so far. Furthermore, the defensin expression and the epithelial integrity are altered in inflammatory bowel diseases and may play an important role in the development of intestinal inflammation. Therefore, it has been hypothesized that the interaction between an altered microbiota composition, a defective epithelial integrity and changes in innate defense parameters such as defensins has a pivotal role in the development of pouchitis in UC patients.

Study Overview

• Status: Unknown
• Conditions: Pouchitis

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: D. Jonkers, PhD; Phone Number: *31-43-3875021; Email: d.jonkers@intmed.unimaas.nl
• Study Contact Backup: Name: M. Pierik, PhD MD; Phone Number: *31-43-3875021; Email: m.pierik@mumc.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6226AZ
      • Maastricht University Medical Center, div. Gastroenterology-Hepatology
      • Contact: D. Jonkers, PhD; Phone Number: *31-43-3875021; Email: d.jonkers@intmed.unimaas.nl
      • Contact: M. Pierik, PhD MD; Phone Number: *31-43-3875021; Email: m.pierik@mumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients undergoing proctocolectomy with the construction of an ileal pouch anal anastomosis will be asked to participate in the study

Description

Inclusion Criteria:

• patients with ulcerative colitis undergoing a total colectomy with IPAA for steroid dependent disease, therapy-refractory disease, colorectal cancer or severe dysplasia
• 18-65 years of age

Exclusion Criteria:

• unable to give informed consent
• pregnant or breastfeeding

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ulcerative colitis patients with a pouch; ulcerative colitis patients undergoing proctocolectomy with an ileal pouch anal anastomosis; comparing patients with versus those without pouchitis; no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in the intestinal microbiota composition between pouch patients with and without pouchitis	A phylogenetic microarray will be used to characterize the luminal and mucosal microbiota composition (based on the SSU rRNA gene)of pouch patients with and without pouchitis. Anticipated results are the identification of specific bacterial profiles, genera and/or species dat are discriminating between subgroups.	24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The expression of defensins in the intestinal mucosa	The mRNA expression levels of human alfa and beta-defensins in intestinal mucosal biopsies will be assessed by real time PCR	24 months
The intestinal permeability	The epithelial integrity will be studied by the multiple sugar test to assess small intestinal and whole gut permeability.	24 months.
Inflammatory mediators	Cytokine levels will be studied in serum and in intestinal biopsies. Furthermore, a histological evaluation and the MPO activity will be studied in these biopsies and calprotectin levels will be determined in 'fecal' sampels.	24 months
The expression of tight-junction associated proteins	The intestinal tight junctions-associated proteins will be studied by immune staining of intestinal biopsies and mRNA levels in intestinal biopsies using real time PCR. Biopsies will be collected from standardised locations.	24 months.

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: A. Masclee, Prof MD PhD, Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Anticipated): November 1, 2014
• Study Completion (Anticipated): November 1, 2015

Study Registration Dates

• First Submitted: September 2, 2010
• First Submitted That Met QC Criteria: September 14, 2010
• First Posted (Estimate): September 15, 2010

Study Record Updates

• Last Update Posted (Estimate): September 15, 2010
• Last Update Submitted That Met QC Criteria: September 14, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: ulcerative colitis; microbiota; pouch; pouchitis; defensins; epithelial integrity
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enteritis; Ileitis; Ileal Diseases; Pouchitis
• Other Study ID Numbers: MEC-10-2-033