Study Finds Gluten, Wheat Safe for Most IBS Patients Despite Self-Perceived Sensitivities

New research is shedding light on the potential safety of gluten and wheat consumption among patients with irritable bowel syndrome (IBS) and self-perceived sensitivities to either ingredient.1

Findings from the randomized, double-blind, sham-controlled crossover study showed only some patients reacted to gluten or wheat. Despite learning that neither gluten nor wheat was triggering their symptoms, most patients continued a gluten-free diet, posing important implications for the potential perpetuation of IBS symptoms, malnutrition, and reduced quality of life.1

“Not every patient who believes they are reacting to gluten actually does,” senior author Premysl Bercik, MD, PhD, a professor in the department of medicine at McMaster University, said in a statement.2 “Some truly have a sensitivity to this food protein, but for many others, it’s the belief itself that’s driving their symptoms and subsequent choices to avoid gluten-containing foods.”

IBS management frequently includes lifestyle changes, particularly as it relates to what patients eat. While the low FODMAP diet is among the most common recommended for individuals with IBS, dietary fiber, gluten, caffeine, fat, dairy, and alcohol are also widely recognized IBS triggers.3 However, evidence about the degree to which these food components exacerbate symptoms and whether patients’ expectations about these dietary triggers contribute to their symptoms and behaviors is not well understood.1

To compare symptomatic responses to wheat and gluten with gluten-free sham challenge in patients with IBS who previously perceived benefit from a gluten-free diet, investigators conducted a randomized, double-blind, sham-controlled crossover study at McMaster University Medical Centre. Eligible participants were adults ≥ 18 years of age who met Rome IV criteria for IBS and had previously self-reported improvement on a gluten-free diet, which was implemented for ≥ 3 weeks before enrollment.1

Eligible participants were randomly assigned in a 1:1:1:1:1:1 ratio to receive 1 of 6 sequences of wheat, gluten, and sham containing gluten and wheat free flour in 3 periods of 7 days, separated by 14-day washout periods. The cereal bars were designed to have the same appearance, taste, and smell to maintain blinding.1

The primary outcome was worsening of IBS symptoms of > 50 points on the IBS Symptom Severity Score (IBS-SSS) after dietary challenges. Outcome and safety analyses were performed in patients who completed all 3 challenges.1

Between Nov 2018, and June 2023, investigators assessed 101 people for eligibility, 29 of whom were enrolled and randomly assigned to wheat–gluten–sham (n = 5), wheat–sham–gluten (n = 5), gluten–wheat–sham (n = 5), gluten– sham–wheat (n = 5), sham–wheat–gluten (n = 5), and sham–gluten–wheat (n = 4). Investigators noted a single participant in the wheat–sham– gluten group completed the first challenge but withdrew without providing a reason, leaving 28 patients who completed the study.1

Due to the COVID-19 pandemic, 14 participants completed the study in-person and 14 completed it online. Of the participants included in the analyses, 26 (93%) were female, 22 (79%) were White, and 17 patients were on a long-term gluten-free diet (median duration, 6.75 years) versus 11 who initiated the gluten-free diet shortly before the study (median duration, 3 weeks).1

Among the 28 patients who completed the study, there were no statistically significant differences in the proportion of participants with a worsening of IBS-SSS of ≥ 50 points after wheat (39%; risk difference vs sham, 0.11; 95% CI, –0.16 to 0.35) or gluten (36%, risk difference, 0.07; 95% CI, –0.19 to 0.32) versus sham (29%). Additionally, according to the IBS-SSS, there were no clinical or statistical differences between wheat (median value at end of challenge, 179.5; 95% CI, 116.0 to 215.0), gluten (166.5; 95% CI, 105.0 to 242.0), or sham challenges (166.0; 95% CI, 92.0 to 255.0).1

Adverse events were reported in 26 (93%) patients after wheat, 26 (93%) patients after gluten, and 26 (93%) patients after sham. Investigators noted study emergent adverse events were similar between challenges, including 5 (18%) patients after wheat, five (18%) patients after gluten, and 7 (25%) patients after sham, with no patients reporting severe adverse events.1

During the baseline visit, 22 of 26 participants who received their personalised study results believed their symptoms were triggered by wheat, 23 by gluten, and 2 by all challenges, including sham. Of these 26 patients, 17 continued the gluten-free diet, while 9 discontinued the gluten-free diet. Additionally, 1 month post-disclosure, neither wheat or gluten responders nor sham responders or non-responders reported changes in their belief in gluten-free diet efficacy, and gluten-free diet adherence and symptoms did not change post-disclosure.1

“What we need to improve in our clinical management of these patients is to work with them further, not just tell them that gluten is not the trigger and move on,” Bercik said.2 “Many of them may benefit from psychological support and guidance to help destigmatize gluten and wheat and reintroduce them safely in their diet.”

References

1. Seiler CL, Rueda GH, Miranda PM, et al. Effect of gluten and wheat on symptoms and behaviours in adults with irritable bowel syndrome: a single-centre, randomised, double-blind, sham-controlled crossover trial. Lancet Gastroenterol Hepatol. https://www.thelancet.com/journals/langas/article/PIIS2468-1253(25)00090-1/abstract

2. McMaster University. Despite Self-Perceived Sensitivities, Study Finds Gluten and Wheat Safe for Many People with IBS. Newswise. July 21, 2025. Accessed July 22, 2025. https://www.newswise.com/articles/despite-self-perceived-sensitivities-study-finds-gluten-and-wheat-safe-for-many-people-with-ibs

3. Monash University. IBS Diet. Accessed July 22, 2025. https://www.monashfodmap.com/ibs-central/diets/