A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: Effects on bowel frequency and intestinal function

Maria I Vazquez Roque, Michael Camilleri, Thomas Christopher Smyrk, Joseph A Murray, Eric Marietta, Jessica O'Neill, Paula Carlson, Jesse Lamsam, Denise Janzow, Deborah Eckert, Duane Burton, Alan R. Zinsmeister

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Abstract

Background & Aims: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) could benefit from a gluten-free diet (GFD). Methods: We performed a randomized controlled 4-week trial of a gluten-containing diet (GCD) or GFD in 45 patients with IBS-D; genotype analysis was performed for HLA-DQ2 and HLA-DQ8. Twenty-two patients were placed on the GCD (11 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive) and 23 patients were placed on the GFD (12 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive). We measured bowel function daily, small-bowel (SB) and colonic transit, mucosal permeability (by lactulose and mannitol excretion), and cytokine production by peripheral blood mononuclear cells after exposure to gluten and rice. We collected rectosigmoid biopsy specimens from 28 patients, analyzed levels of messenger RNAs encoding tight junction proteins, and performed H&E staining and immunohistochemical analyses. Analysis of covariance models was used to compare data from the GCD and GFD groups. Results: Subjects on the GCD had more bowel movements per day (P =.04); the GCD had a greater effect on bowel movements per day of HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P =.019). The GCD was associated with higher SB permeability (based on 0-2 h levels of mannitol and the lactulose:mannitol ratio); SB permeability was greater in HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P =.018). No significant differences in colonic permeability were observed. Patients on the GCD had a small decrease in expression of zonula occludens 1 in SB mucosa and significant decreases in expression of zonula occludens 1, claudin-1, and occludin in rectosigmoid mucosa; the effects of the GCD on expression were significantly greater in HLA-DQ2/8-positive patients. The GCD vs the GFD had no significant effects on transit or histology. Peripheral blood mononuclear cells produced higher levels of interleukin-10, granulocyte colony-stimulating factor, and transforming growth factor-α in response to gluten than rice (unrelated to HLA genotype). Conclusions: Gluten alters bowel barrier functions in patients with IBS-D, particularly in HLA-DQ2/8-positive patients. These findings reveal a reversible mechanism for the disorder. Clinical trials.gov NCT01094041.

Original languageEnglish (US)
JournalGastroenterology
Volume144
Issue number5
DOIs
StatePublished - May 2013

Fingerprint

Gluten-Free Diet
Glutens
Irritable Bowel Syndrome
Diarrhea
Diet
Permeability
Mannitol
Lactulose
Tight Junctions
Blood Cells
Mucous Membrane
Genotype
Claudin-1
Occludin
Tight Junction Proteins
Transforming Growth Factors
Granulocyte Colony-Stimulating Factor
Interleukin-10
Histology

Keywords

  • Cytokines
  • Immunity
  • Permeability
  • Transit

ASJC Scopus subject areas

  • Gastroenterology

Cite this

A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea : Effects on bowel frequency and intestinal function. / Vazquez Roque, Maria I; Camilleri, Michael; Smyrk, Thomas Christopher; Murray, Joseph A; Marietta, Eric; O'Neill, Jessica; Carlson, Paula; Lamsam, Jesse; Janzow, Denise; Eckert, Deborah; Burton, Duane; Zinsmeister, Alan R.

In: Gastroenterology, Vol. 144, No. 5, 05.2013.

Research output: Contribution to journalArticle

Vazquez Roque, Maria I ; Camilleri, Michael ; Smyrk, Thomas Christopher ; Murray, Joseph A ; Marietta, Eric ; O'Neill, Jessica ; Carlson, Paula ; Lamsam, Jesse ; Janzow, Denise ; Eckert, Deborah ; Burton, Duane ; Zinsmeister, Alan R. / A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea : Effects on bowel frequency and intestinal function. In: Gastroenterology. 2013 ; Vol. 144, No. 5.
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abstract = "Background & Aims: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) could benefit from a gluten-free diet (GFD). Methods: We performed a randomized controlled 4-week trial of a gluten-containing diet (GCD) or GFD in 45 patients with IBS-D; genotype analysis was performed for HLA-DQ2 and HLA-DQ8. Twenty-two patients were placed on the GCD (11 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive) and 23 patients were placed on the GFD (12 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive). We measured bowel function daily, small-bowel (SB) and colonic transit, mucosal permeability (by lactulose and mannitol excretion), and cytokine production by peripheral blood mononuclear cells after exposure to gluten and rice. We collected rectosigmoid biopsy specimens from 28 patients, analyzed levels of messenger RNAs encoding tight junction proteins, and performed H&E staining and immunohistochemical analyses. Analysis of covariance models was used to compare data from the GCD and GFD groups. Results: Subjects on the GCD had more bowel movements per day (P =.04); the GCD had a greater effect on bowel movements per day of HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P =.019). The GCD was associated with higher SB permeability (based on 0-2 h levels of mannitol and the lactulose:mannitol ratio); SB permeability was greater in HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P =.018). No significant differences in colonic permeability were observed. Patients on the GCD had a small decrease in expression of zonula occludens 1 in SB mucosa and significant decreases in expression of zonula occludens 1, claudin-1, and occludin in rectosigmoid mucosa; the effects of the GCD on expression were significantly greater in HLA-DQ2/8-positive patients. The GCD vs the GFD had no significant effects on transit or histology. Peripheral blood mononuclear cells produced higher levels of interleukin-10, granulocyte colony-stimulating factor, and transforming growth factor-α in response to gluten than rice (unrelated to HLA genotype). Conclusions: Gluten alters bowel barrier functions in patients with IBS-D, particularly in HLA-DQ2/8-positive patients. These findings reveal a reversible mechanism for the disorder. Clinical trials.gov NCT01094041.",
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AU - Camilleri, Michael

AU - Smyrk, Thomas Christopher

AU - Murray, Joseph A

AU - Marietta, Eric

AU - O'Neill, Jessica

AU - Carlson, Paula

AU - Lamsam, Jesse

AU - Janzow, Denise

AU - Eckert, Deborah

AU - Burton, Duane

AU - Zinsmeister, Alan R.

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N2 - Background & Aims: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) could benefit from a gluten-free diet (GFD). Methods: We performed a randomized controlled 4-week trial of a gluten-containing diet (GCD) or GFD in 45 patients with IBS-D; genotype analysis was performed for HLA-DQ2 and HLA-DQ8. Twenty-two patients were placed on the GCD (11 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive) and 23 patients were placed on the GFD (12 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive). We measured bowel function daily, small-bowel (SB) and colonic transit, mucosal permeability (by lactulose and mannitol excretion), and cytokine production by peripheral blood mononuclear cells after exposure to gluten and rice. We collected rectosigmoid biopsy specimens from 28 patients, analyzed levels of messenger RNAs encoding tight junction proteins, and performed H&E staining and immunohistochemical analyses. Analysis of covariance models was used to compare data from the GCD and GFD groups. Results: Subjects on the GCD had more bowel movements per day (P =.04); the GCD had a greater effect on bowel movements per day of HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P =.019). The GCD was associated with higher SB permeability (based on 0-2 h levels of mannitol and the lactulose:mannitol ratio); SB permeability was greater in HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P =.018). No significant differences in colonic permeability were observed. Patients on the GCD had a small decrease in expression of zonula occludens 1 in SB mucosa and significant decreases in expression of zonula occludens 1, claudin-1, and occludin in rectosigmoid mucosa; the effects of the GCD on expression were significantly greater in HLA-DQ2/8-positive patients. The GCD vs the GFD had no significant effects on transit or histology. Peripheral blood mononuclear cells produced higher levels of interleukin-10, granulocyte colony-stimulating factor, and transforming growth factor-α in response to gluten than rice (unrelated to HLA genotype). Conclusions: Gluten alters bowel barrier functions in patients with IBS-D, particularly in HLA-DQ2/8-positive patients. These findings reveal a reversible mechanism for the disorder. Clinical trials.gov NCT01094041.

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KW - Permeability

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