Diet Based on Confocal Laser Endomicroscopy Did Not Improve Irritable Bowel Syndrome Symptoms: A Randomized Controlled Crossover Trial

L Balsiger et al. Gastroenterology, 2026. Individualized Targeted Exclusion Diet Based on Confocal Laser Endomicroscopy Does Not Improve Irritable Bowel Syndrome Symptoms: A Randomized Controlled Crossover Trial

While foods often trigger IBS symptoms, there has not been a simple way to identify these foods with objective testing. Previous small studies have indicated that confocal laser endomicroscopy has the potential to identify these triggers (See prior post: Is There a Way to Prove Which Dietary Factors Trigger Irritable Bowel Syndrome?).

“The advent of confocal laser endomicroscopy (CLE) has enabled in vivo real-time visualization of the gastrointestinal mucosa.9 Using this approach, researchers have demonstrated acute food-induced mucosal alterations in the duodenum of patients with IBS.10,11 …The reliable identification of foods responsible for symptoms in individual patients with IBS is of great interest. Not only would it streamline the current trial-and-error approach, but it could also potentially avoid overly restrictive dietary patterns, which potentially can lead to avoidant restrictive food intake disorder.”

Methods: “This was a double-blind, controlled, crossover study in patients with IBS. After CLE, patients excluded up to 2 foods that did (= real diet) and up to 2 foods that did not (= sham diet) cause alterations in a randomized order. Diets were followed for 4 weeks each. Clinical response was defined as improving ≥50 points on the IBS Symptom Severity Score. Healthy controls underwent the same CLE protocol as patients with IBS.” 31 patients (median age 33 years) completed both phases of dietary interventions.

Key findings:

  • Clinical response rates were not different between real and sham diet (42% vs 36%; odds ratio, 1.33; P = .6). Symptoms improved both on the real and the sham diet (−30 vs −20; P = .7). 
  • In 15 healthy volunteers, altered mucosa was visualized in 100% of the examinations either at baseline (13%) or after food administration.

My take: CLE-based tailored diet was not beneficial compared to a sham diet. In addition, CLE changes were present in all of the healthy volunteers indicating that altered mucosa is a nonspecific reaction rather than pathognomonic IBS reaction. Thus, there remains no proven way to identify trigger foods in IBS. Exclusion diets can improve symptoms but require careful monitoring.

Related blog posts:

Is There a Way to Prove Which Dietary Factors Trigger Irritable Bowel Syndrome?

In a recent study (A Fritscher-Ravens et al. Gastroenterol 2019; 157: 109-18) uses confocal laser endomicroscopy (CLE) for “real-time detection and quantification of changes in intestinal tissues” related to food challenges. The authors previously had used this technique in a feasibility study (Gastroenterol 2014; 147: 1012-20). In this study, two-thirds of patients with CLE+ IBS showed improvement of IBS symptoms after a 12-month exclusion diet.

In the current study, the authors prospectively examined patients (n=108 completed study) who had irritable bowel syndrome and were convinced that this was triggered by foods (with negative IgE food allergy testing).  The CLE testing evaluated four food components

Key findings:

  • 76 of 108 (70%) had abnormal CLE; 46 of these reactions were to wheat
  • In those with CLE+ reactions, intraepithelial lymphocytes were significantly higher compared to those with CLE-negative (normal evaluations).
  • Other biomarkers associated with CLE+ included increased claudin-2 expression from crypt to villous tip, lower levels of occludin, and higher eosinophilic cationic protein.

Abnormal CLE indicated abnormal mucosal appearance including formation of epithelial leaks/gaps and widening of the intervillous spaces after food challenge.

My take: This study shows that in individuals with a strong suspicion of food-triggered IBS, immediate reactions in the mucosa can be detected with CLE in more than 50%. Whether this type of approach could/should be developed for wider use in targeting a specific diet is unclear.  More studies are needed.

Related blog posts:

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