Gluten Intolerance in Patients With Diarrhea Predominant Irritable Bowel Syndrome

The study design is a double-blind, randomized, controlled, parallel-group, 6-week study comparing the effects of gluten rich versus gluten free diets in diarrhea or diarrhea predominant IBS patients. All participants will keep a daily bowel pattern diary throughout the study. All participants will have negative serum tissue transglutaminase (TTg) assay, and anti-endomysial antibody test, if TTg is positive or equivocal. All participants will have the following studies performed both before and after the 4-week dietary intervention:

• Stool samples to check markers of inflammation such as fecal calprotectin.
• Blood samples to check markers of inflammation and for genetic testing.
• After ingestion of the mannitol, lactulose and sucralose sugars, urine samples to indirectly measure small intestinal and colonic permeability.
• After sedation, upper gastrointestinal endoscopy and flexible sigmoidoscopy to obtain 6 mucosal biopsies from the small bowel and sigmoid colon for immunohistochemical analysis.
• Scintigraphy to measure gastrointestinal transit.

Inclusion criteria

• Diarrhea or diarrhea predominant IBS patients
• Age 18 to 65
• BDQ confirms presence of IBS-D or functional diarrhea, positive by Rome III criteria
• No restrictions on Hospital Anxiety Depression score
• No abdominal surgery (except appendectomy and cholecystectomy)

Exclusion criteria

• Serum tissue transglutaminase IgA or IgG positive or medical record of small bowel biopsy suggestive of celiac disease
• Use of tobacco products within the past 6 months (since nicotine may affect intestinal permeability)
• Use of NSAIDs or aspirin within the past week (since NSAIDs affect intestinal permeability)
• Use of oral corticosteroids within the previous 6 weeks
• Ingestion of artificial sweeteners such as SplendaTM (sucralose), Nutrasweet TM(aspartame), lactulose or mannitol 2 days before the study begins, e.g., foods to be avoided are sugarless gums or mints and diet soda
• Ingestion of any prescription, over the counter, or herbal medications which can affect gastrointestinal transit 7 days before study begins.
• Any females who are pregnant or trying to become pregnant (due to radiation exposure)
• Bleeding disorders or medications that increase risk of bleeding from mucosal