PPCD: Gut Peptides and Intestinal Permeability in Celiac Disease and Irritable Bowel Syndrome
Study Details
Study Description
Brief Summary
It is well known that the intestinal barrier is altered in celiac disease (CD), an autoimmune disease that develops in genetically predisposed subjects exposed to ingestion of wheat gliadin and of related prolamines of barley and rye. More recently, defective epithelial barrier has been implicated in the pathogenesis of other conditions such as irritable bowel syndrome (IBS). At present IBS is still considered a functional condition although low-grade inflammation has been associated with its manifestation, particularly that following infection. Different substances have been implicated in the (dis)regulation of intestinal barrier, among them zonulin seems to play a key role. Other gastrointestinal peptides are GPL-2, Ghrelin, and Epidermal growth factor (EGF). In order to shed light on the hormonal regulation of intestinal barrier function in celiac patients before undergoing a gluten free diet and possible differences with those of IBS patients, in the present study the investigators will apply the non-invasive lactulose/mannitol permeability test toward the evaluation of intestinal damage. The pattern of intestinal permeability and the GI peptides concentration will be compared in celiac patients, IBS patients and healthy controls.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Celiac Disease Patients suffering from coeliac diseases confirmed by small intestinal biopsy |
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| IBS patients Patients suffering from irritable bowel syndrome (IBS) according to Rome III criteria |
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| Healthy subjects Healthy subjects as control group |
Outcome Measures
Primary Outcome Measures
- Plasma concentrations of GI peptides (Zonulin, GLP-2, Ghrelin and EGF) [within one month after the enrollment]
Secondary Outcome Measures
- Intestinal permeability [within one month after the enrollment]
The detection and measurement of two sugar probes, lactulose (La) and mannitol (Ma), in the urine will be performed by chromatographic analysis. For each sample the percentage of ingested La and Ma in urine will be evaluated and their ratio (La-Ma) will be calculated.
Eligibility Criteria
Criteria
Inclusion criteria of celiac disease patients:
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Diagnosis of CD was based on the detection of IgA antiendomysial and IgA antitissue transglutaminase antibodies in serum
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Diagnosis must be confirmed by a small intestinal biopsy obtained at the time of gastrointestinal endoscopy.
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All patients must show Marsh 3 grade villous atrophy at the time of the diagnosis.
Inclusion criteria of IBS patients.
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Subjects suffering from irritable bowel syndrome according to the Rome III criteria.
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Availability of at least one GI imaging study during the last five years (colonoscopy, sigmoidoscopy, abdominal ultrasound, barium enema)
Exclusion criteria for both the above groups:
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None were taking anti-inflammatory drugs (including mast cell stabilisers, histamine antagonists, anticholinergics, anti-diarrhoea medication, probiotics, immunosuppressants and steroids)
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Presence of organic syndrome, including food allergy, atopy and severe clinical depression or anxiety.
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Abnormal laboratory data or thyroid function
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Major abdominal surgery Healthy subjects will be recruited in the administrative staff of the Institute after thorough exclusion of GI symptoms.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Institute of Digestive Diseases IRCCS "S. de Bellis" | Castellana Grotte | Bari | Italy | 70013 |
Sponsors and Collaborators
- Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
Investigators
- Principal Investigator: Giuseppe Riezzo, MD, National Institute of Digestive Diseases IRCCS "S. de Bellis"
Study Documents (Full-Text)
None provided.More Information
Publications
- Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009 Aug;58(8):1091-103. doi: 10.1136/gut.2008.165886. Epub 2009 Feb 24.
- Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75. doi: 10.1152/physrev.00003.2008. Review.
- Gecse K, Róka R, Séra T, Rosztóczy A, Annaházi A, Izbéki F, Nagy F, Molnár T, Szepes Z, Pávics L, Bueno L, Wittmann T. Leaky gut in patients with diarrhea-predominant irritable bowel syndrome and inactive ulcerative colitis. Digestion. 2012;85(1):40-6. doi: 10.1159/000333083. Epub 2011 Dec 14.
- Malandrino N, Capristo E, Farnetti S, Leggio L, Abenavoli L, Addolorato G, Gasbarrini G. Metabolic and nutritional features in adult celiac patients. Dig Dis. 2008;26(2):128-33. doi: 10.1159/000116770. Epub 2008 Apr 21. Review.
- Ménard S, Lebreton C, Schumann M, Matysiak-Budnik T, Dugave C, Bouhnik Y, Malamut G, Cellier C, Allez M, Crenn P, Schulzke JD, Cerf-Bensussan N, Heyman M. Paracellular versus transcellular intestinal permeability to gliadin peptides in active celiac disease. Am J Pathol. 2012 Feb;180(2):608-15. doi: 10.1016/j.ajpath.2011.10.019. Epub 2011 Nov 24.
- CD5X1000