The Interaction Between Intestinal Microbiota, Innate Defense and Epithelial Integrity in the Development of Pouchitis
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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 |
Outcome Measures
Primary Outcome Measures
- Differences in the intestinal microbiota composition between pouch patients with and without pouchitis [24 months.]
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.
Secondary Outcome Measures
- The expression of defensins in the intestinal mucosa [24 months]
The mRNA expression levels of human alfa and beta-defensins in intestinal mucosal biopsies will be assessed by real time PCR
- The intestinal permeability [24 months.]
The epithelial integrity will be studied by the multiple sugar test to assess small intestinal and whole gut permeability.
- Inflammatory mediators [24 months]
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.
- The expression of tight-junction associated proteins [24 months.]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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patients with ulcerative colitis undergoing a total colectomy with IPAA for steroid dependent disease, therapy-refractory disease, colorectal cancer or severe dysplasia
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18-65 years of age
Exclusion Criteria:
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unable to give informed consent
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pregnant or breastfeeding
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Maastricht University Medical Center, div. Gastroenterology-Hepatology | Maastricht | Limburg | Netherlands | 6226AZ |
Sponsors and Collaborators
- Maastricht University Medical Center
Investigators
- Principal Investigator: A. Masclee, Prof MD PhD, Maastricht University Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MEC-10-2-033