Individualized targeted exclusion diet based on confocal laser endomicroscopy does not improve irritable bowel syndrome symptoms: a randomized controlled crossover trial

BACKGROUND & AIMS: In the duodenum of patients with irritable bowel syndrome (IBS), acute food‐induced mucosal reactions have been visualized using confocal laser endomicroscopy (CLE). In uncontrolled studies, a diet excluding trigger foods led to symptomatic improvement. Here, we aim to assess the association of food‐induced alterations identified using CLE and the efficacy of a targeted diet in a controlled study. 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. RESULTS: Altered mucosa was visualized in all patients either before (11%) or after food administration. 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). Also, in 15 healthy volunteers, altered mucosa was visualized in 100% of the examinations either at baseline (13%) or after food administration. CONCLUSIONS: Acute alterations visualized using CLE have poor sensitivity and specificity for dietary responses in IBS patients. Moreover, altered mucosa was present in 100% of healthy volunteers and likely represents a nonspecific mucosal reaction to food exposure rather than pathology, challenging the use of CLE in clinical practice to identify culprit foods. (ClinicalTrials.gov, Number: NCT05097872).