The specific hypotheses are: Gluten supplementation for four weeks increases small intestinal permeability and accelerates colonic transit in patients with irritable bowel syndrome with diarrhea (IBS-D) or functional diarrhea (FD) who are HLA-DQ2 positive.
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: 1. Stool samples to check markers of inflammation such as fecal calprotectin. 2. Blood samples to check markers of inflammation and for genetic testing. 3. After ingestion of the mannitol, lactulose and sucralose sugars, urine samples to indirectly measure small intestinal and colonic permeability. 4. After sedation, upper gastrointestinal endoscopy and flexible sigmoidoscopy to obtain 6 mucosal biopsies from the small bowel and sigmoid colon for immunohistochemical analysis. 5. Scintigraphy to measure gastrointestinal transit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
50
A 4-week gluten free diet provided
A 4-week gluten rich diet is provided
Mayo Clinic
Rochester, Minnesota, United States
Small bowel permeability
Excretion of mannitol 0-2 hours after liquid formulation
Time frame: 0 - 2 hours post sugar ingestion
Colonic permeability
Cumulative excretion of mannitol at 2-24 hours after liquid
Time frame: 2 -24 hours post sugars ingestion
Colonic transit
Colonic transit geometric center at 24 hours
Time frame: 24 hours
Colon transit
Ascending colon emptying T1/2
Time frame: 6-12 hours
Colonic permeability
Cumulative excretion of lactulose
Time frame: 2-24 hours after sugars ingestion
Colonic permeability
Hourly excretion of mannitol
Time frame: 8 to 24 hours after ingestion of sugars
Small bowel transit time
Colonic filling at 6 hours (%)
Time frame: 6 hours
Gastric emptying
Gastric emptying T1/2
Time frame: 0-2 hours
Colonic inflammatory response
Sigmoid colon mucosal immunocyte count in lamina propria
Time frame: 4 weeks
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Stool frequency and consistency
Bowel pattern diary
Time frame: 6 weeks
Small bowel inflammatory response
Duodenal mucosal immunocyte count in lamina propria
Time frame: 4 weeks