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TOPLINE:

Patients with irritable bowel syndrome (IBS) who believe that gluten or wheat trigger their symptoms showed similar reactions to gluten, wheat, and gluten-free sham challenges, which suggested that expectations drove most of their symptoms and that only a few might truly benefit from dietary restrictions. 

METHODOLOGY:

• Many patients with IBS believe that gluten or wheat triggers their symptoms and switch to gluten-free diets, but it remains unclear whether these symptoms are caused by the substances or by patients’ expectation of a reaction.
• Researchers conducted a double‐blind, sham‐controlled, crossover study to compare symptomatic responses to wheat, gluten, and gluten‐free sham challenges in patients with IBS who had previously perceived benefits from a gluten‐free diet.
• They randomly assigned 28 patients (median age, 39 years; 93% women) who were on a gluten-free diet for at least 3 weeks before enrollment to one of six sequences (wheat-gluten-sham, wheat-sham-gluten, gluten-wheat-sham, gluten-sham-wheat, sham-wheat-gluten, and sham-gluten-wheat).
• For each challenge, patients consumed one cereal bar daily — either containing whole wheat, purified gluten, or gluten- and wheat-free flour — in three 7-day periods, each separated by a 14-day washout.
• The primary outcome was a worsening of symptoms, defined as an increase of at least 50 points in the IBS Symptom Severity Score after each dietary challenge.

TAKEAWAY:

• Among the participants, 39% experienced worsening symptoms after the wheat challenge, 36% after the gluten challenge, and 29% after the sham challenge. In all, 36% of patients did not report symptom worsening after any challenge.
• There were no statistically significant differences between challenges (risk difference, 0.11 for wheat vs sham and 0.07 for gluten vs sham).
• Moreover, there was no significant difference in median IBS Symptom Severity Scores at the end of each challenge: wheat (179.5), gluten (166.5), and sham (166).
• Adverse events occurred at similar rates across challenges (five with wheat, five with gluten, and seven with sham). None of the patients reported severe adverse events.
• Most patients continued a gluten-free diet and believed gluten or wheat were triggers, even after learning that challenges did not worsen symptoms.

IN PRACTICE:

“These findings suggest that expectations played a major role in symptom generation, and that only some of these patients could benefit from gluten or wheat restriction. Identifying this subset of patients while destigmatizing wheat and gluten in the remaining ones should be considered for effective management of patients with IBS,” the authors of the study wrote.

“[This] study represents a valuable step forward in highlighting expectancy effects in IBS…It offers insights for both researchers and clinicians and shows the potential for integrating expectancy research into dietary and pharmacological treatment strategies. Improved patient-provider communication could enhance patient management. As psychology and gastroenterology continue to converge, interdisciplinary collaboration will be key to personalizing treatment and improving patient outcomes in disorders of gut-brain interaction and other conditions in gastroenterology,” Sigrid Elsenbruch, PhD, professor at the Center for Translational and Neuro- and Behavioral Sciences, Essen, Germany, wrote in an accompanying editorial.

SOURCE:

This study, led by Caroline Larissa Seiler, PhD, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada, was published online in The Lancet Gastroenterology & Hepatology.

LIMITATIONS:

IBS is highly heterogeneous and prone to placebo or nocebo effects, so larger trials are needed for definitive results and safety data. Including both experienced patients and recent gluten-free diet initiators may have introduced variability. A predominantly female and White cohort may have limited generalizability. Subgroup analyses by IBS type were not conducted due to underpowering.

DISCLOSURES:

This study received funding from the Canadian Digestive Health Foundation and the Society for the Study of Celiac Disease. Some authors reported receiving honoraria, payment, consulting fees, or grants from and having other ties with several pharmaceutical companies and other organizations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.