A Controlled Trial of Gluten-Free Diet in Patients With Irritable Bowel Syndrome-Diarrhea: Effects on Bowel Frequency and Intestinal Function

doi:10.1053/j.gastro.2013.01.049

Gastroenterology

Volume 144, Issue 5, May 2013, Pages 903-911.e3

https://doi.org/10.1053/j.gastro.2013.01.049 Get rights and content

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.

Section snippets

Study Design and Intervention

Between January 2010 and February 2012, we conducted a single-center, parallel-group, randomized, controlled, 4-week trial of GCD and GFD in 45 gluten-ingesting patients with IBS-D. They were recruited from a database of more than 800 patients with IBS who had been evaluated clinically by the investigators or clinical staff at Mayo Clinic. These patients reside within 150 miles of Mayo Clinic in Rochester, Minnesota, and the database is maintained in the laboratory of the principal

Demographics and Baseline Characteristics

Supplementary Figure 1 shows the trial flow and summarizes the baseline demographic data. There were no differences in age, sex distribution, Hospital Anxiety and Depression scores, body mass index, baseline 0–2 hour excretion of mannitol and lactulose, and baseline colonic transit in the groups assigned to each diet. As expected in this patient population, there was a female predominance.

The prestudy diet questionnaire showed that the patients were not ingesting a gluten-free diet before the

Discussion

In this 4-week, randomized, controlled, diet intervention study, the intervention was associated with several significant effects. Subjects on a GCD had increased stool frequency compared with a GFD; this effect was greater in HLA-DQ2– or HLA-DQ8–positive patients. Although the absolute difference in stool frequency was small, it is important to appreciate that this increased frequency is on a background of the typical increase in stool frequency (average, 2.6 bowel movements/day at baseline)

Acknowledgments

The authors thank Michael Ryks and Debbie Rhoten for technical support, and Cindy Stanislav for secretarial assistance.

Maria Vazquez-Roque was the fellow investigator, and was responsible for participant recruitment and wrote the article; Michael Camilleri was the principal investigator, wrote the protocol, and wrote the article; Thomas Smyrk was responsible for surgical pathology; Joseph Murray wrote the article; Jessica O'Neill was the study coordinator and was responsible for participant

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Sieving out non-celiac gluten sensitivity amongst patients with irritable bowel syndrome
2024, Digestive and Liver Disease
It is challenging to make diagnosis of non-celiac gluten sensitivity/non-celiac wheat sensitivity (NCGS/NCWS) in clinical practice, since there is no biomarker and diagnosis is based on response to gluten-free-diet (GFD). We used anti-gliadin antibody (AGA) for screening patients with IBS for gluten-sensitivity.
492 Adult-patients with IBS underwent screening for celiac disease and gluten-sensitivity using IgA anti-tissue transglutaminase antibody and IgA-AGA and IgG-AGA, respectively. Patients with positive AGA (IgA and/or IgG) were invited to follow GFD, those willing were put on GFD for 6-weeks. Responsive patients were given gluten re-challenge. Diagnosis of NCGS was confirmed if they had recurrence of symptoms.
Of 492 patients with IBS, AGA was positive in 61(12.4 %), hence suspected to have gluten-sensitivity. Of 31 who agreed to participate and followed GFD for 6-weeks, 17 (54.8 %) had complete (>30 % improvement) and 10(32.2 %) had partial (>20 % improvement) response. All 17 complete-responders were given gluten re-challenge for 6-weeks, symptoms recurred in all and hence were confirmed to have NCGS/NCWS. Significant decrease in AGA levels occurred almost in all GFD-responders.
12.4 % IBS patients have biological evidence of gluten/wheat-sensitivity. Almost 87 % patients with IBS having AGA responded to GFD. The value of AGA may further be explored as a biomarker for screening for the presence of NCGS, before recommending this test for the clinical practice.
Dietary Interventions and Brain–Gut Disorders
2024, The Gut-Brain Axis, Second Edition
Several lines of evidence suggest that the gut microbiome may represent a valid target for new therapeutic interventions in relation to disorders of the gut–brain axis. Indeed, the concept of a microbiome–gut–brain axis has gained considerable traction in recent years. While several diseases and disorders may reflect disruption of, or dysfunction along, the microbiome–gut–brain axis this chapter will focus on one very common and challenging disorder long perceived as representing dysfunction along the gut–brain axis: irritable bowel syndrome (IBS). Recognizing the frequency with which patients report exacerbation of their IBS symptoms on eating there has been, of late considerable interest in diet in the treatment of IBS. A variety of dietary approaches have been advocated with the diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) achieving most traction. The physiological basis for its efficacy as well as evidence to support its efficacy are reviewed. While comparisons between the low FODMAP diet and other dietary approaches to IBS have yielded variable results, interest in the gluten-free diet has receded somewhat though it may be of benefit to certain select populations. Various therapeutic strategies have been employed to address gut microbial factors that may contribute to IBS and include probiotics, prebiotics, and postbiotics. With regard to prebiotics and probiotics, while a considerable volume of experimental data attests to their ability to address various pathophysiologic parameters relevant to IBS, the interpretation of clinical trials continues to pose challenges. Thus, while probiotics, in general, appear to be beneficial in IBS, less is known about ideal strain, preparation, and dosage; for prebiotics and postbiotics, data are scant but appear promising. More high-quality clinical trials are needed.
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La perméabilité intestinale est liée au passage des nutriments et des électrolytes au travers de l’épithélium intestinal, soit par voie paracellulaire, soit par voie transcellulaire. Elle est altérée par l’inflammation et la destruction de l’épithélium intestinal, comme au cours des entéropathies auto-immunes. Le transport transcellulaire des peptides de gluten non dégradés dans le chorion est une particularité de la maladie cœliaque active. Il est responsable de l’activation de la réponse immune adaptative qui participe à la destruction de l’épithélium. Des altérations minimes de la perméabilité paracellulaire ont été décrites au cours de l’hypersensibilité au gluten, comme au cours de l’ensemble des troubles fonctionnels intestinaux à tendance diarrhéique.
Intestinal permeability allows transfer of nutrients and electrolytes through the epithelial paracellular and transcellular route. It is altered by inflammation and lesion of the intestinal epithelium as observed in autoimmune enteropathy. Transcellular transport of undegraded gluten peptides into the chorion is a specific feature of active coeliac disease. It induces activation of the adaptive immune response involved in the epithelium destruction. Slight alterations in paracellular permeability have been described in non-coeliac gluten sensitivity as well as in several functional intestinal disorders with diarrheal tendency.
Approach to Disorders of Gut-Brain Interaction
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Disorders of gut-brain interaction, previously known as functional gastrointestinal disorders (eg, functional dyspepsia and irritable bowel syndrome), are commonly encountered in both the primary care and gastroenterology clinics. These disorders are often associated with high morbidity and poor patient quality of life and often lead to increased health care use. The management of these disorders can be challenging, as patients often present after having undergone an extensive workup without a definite etiology. In this review, we provide a practical five-step approach to the clinical assessment and management of disorders of gut-brain interaction. The five-step approach includes (1) excluding organic etiologies of the patient’s symptoms and using Rome IV criteria for diagnosis, (2) empathizing with the patient to develop trust and a therapeutic relationship, (3) educating the patient about the pathophysiology of these gastrointestinal disorders, (4) expectation setting with a focus on improving function and quality of life, and (5) establishing a treatment plan with central and peripherally acting medications and nonpharmacological modalities. We discuss the pathophysiology of disorders of gut-brain interaction (eg, visceral hypersensitivity), initial assessment and risk stratification, as well as treatment for a variety of diseases with a focus on irritable bowel syndrome and functional dyspepsia.
Diet for Functional Gastrointestinal Disorders/Disorders of Gut–Brain Interaction
2022, Medical Clinics of North America
AGA Clinical Practice Update on the Role of Diet in Irritable Bowel Syndrome: Expert Review
2022, Gastroenterology
Irritable bowel syndrome (IBS) is a commonly diagnosed gastrointestinal disorder that can have a substantial impact on quality of life. Most patients with IBS associate their gastrointestinal symptoms with eating food. Mounting evidence supports dietary modifications, such as the low–fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet, as a primary treatment for IBS symptoms. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) is to provide best practice advice statements, primarily to clinical gastroenterologists, covering the role of diet in IBS treatment.
This expert review was commissioned and approved by the AGA CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Gastroenterology. The best practice advice statements were drawn from reviewing existing literature combined with expert opinion to provide practical advice on the role of diet in treating patients with IBS. Because this was not a systematic review, formal rating of the quality of evidence or strength of the presented considerations was not performed.
Best Practice Advice Statements
Dietary advice is ideally prescribed to patients with IBS who have insight into their meal-related gastrointestinal symptoms and are motivated to make the necessary changes. To optimize the quality of teaching and clinical response, referral to a registered dietitian nutritionist (RDN) should be made to patients who are willing to collaborate with a RDN and patients who are not able to implement beneficial dietary changes on their own. If a gastrointestinal RDN is not available, other resources can assist with implementation of diet interventions.
Patients with IBS who are poor candidates for restrictive diet interventions include those consuming few culprit foods, those at risk for malnutrition, those who are food insecure, and those with an eating disorder or uncontrolled psychiatric disorder. Routine screening for disordered eating or eating disorders by careful dietary history is critical because they are common and often overlooked in gastrointestinal conditions.
Specific diet interventions should be attempted for a predetermined length of time. If there is no clinical response, the diet intervention should be abandoned for another treatment alternative, for example, a different diet, medication, or other form of therapy.
In preparation for a visit with a RDN, patients should provide dietary information that will assist in developing an individualized nutrition care plan.
Soluble fiber is efficacious in treating global symptoms of IBS.
The low-FODMAP diet is currently the most evidence-based diet intervention for IBS. Healthy eating advice as described by the National Institute of Health and Care Excellence Guidelines, among others, also offers benefit to a subset of patients with IBS.
The low-FODMAP diet consists of the following 3 phases: 1) restriction (lasting no more than 4–6 weeks), 2) reintroduction of FODMAP foods, and 3) personalization based on results from reintroduction.
Although observational studies found that most patients with IBS improve with a gluten-free diet, randomized controlled trials have yielded mixed results.
There are limited data showing that selected biomarkers can predict response to diet interventions in patients with IBS, but there is insufficient evidence to support their routine use in clinical practice.

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: Conflicts of interest This author discloses the following: Joseph Murray has received grants from Alba Therapeutics for clinical trials with the drug larazotide. The remaining authors disclose no conflicts.

: Funding This study was supported in part by National Institutes of Health grants 1RC1-DK086182 and R01-DK092179 (M.C.) and by a National Institutes of Health Clinical Translational Science Awards Program grant (UL1 TR000135).

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Original ResearchFull Report: Clinical—Alimentary TractA Controlled Trial of Gluten-Free Diet in Patients With Irritable Bowel Syndrome-Diarrhea: Effects on Bowel Frequency and Intestinal Function

Background & Aims

Methods

Results

Conclusions

Section snippets

Study Design and Intervention

Demographics and Baseline Characteristics

Discussion

Acknowledgments

Gastroenterology

Clin Gastroenterol Hepatol

Am J Clin Nutr

Mayo Clin Proc

Gastroenterology

Clin Biochem

FEBS Lett

Pain

Hum Immunol

Gastroenterology

Gliadin-dependent neuromuscular and epithelial secretory responses in gluten-sensitive HLA-DQ8 transgenic mice

Am J Physiol

Urine sugars for in vivo gut permeability: validation and comparisons in irritable bowel syndrome-diarrhea and controls

Am J Physiol

The jejunum of diarrhea-predominant irritable bowel syndrome shows molecular alterations in the tight junction signaling pathway that are associated with mucosal pathobiology and clinical manifestations

Am J Gastroenterol

Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes

Am J Gastroenterol

Original Research
Full Report: Clinical—Alimentary Tract
A Controlled Trial of Gluten-Free Diet in Patients With Irritable Bowel Syndrome-Diarrhea: Effects on Bowel Frequency and Intestinal Function