After a thorough baseline evaluation, IBS patients will be exposed to nutrients while undergoing confocal laser endomicroscopy (CLE). Patients presenting an acute mucosal reaction upon nutrient exposure will be instructed to exclude their respective trigger nutrient or a nutrient without mucosal reaction (=sham diet) from their diet for 4 weeks in a randomized, blinded crossover fashion.

The aim of the trial is to assess the symptomatic response to the targeted diet and further elucidate mechanisms underlying the acute mucosal reactions observed in CLE upon nutrient exposure.

Inclusion Criteria:

• Age 18-70 y/o (70 years included)
• Male or female subjects
• IBS-D and IBS-M (i.e. IBS-non-C) according to Rome IV criteria
• Moderate to severe symptom severity as defined by the Irritable bowel syndrome severity scoring system (IBS-SSS) (i.e. IBS-SSS >175 points)
• Provide written informed consent to participate in the study
• Women of child-bearing potential agree to apply a highly effective method of birth control during the entire duration of the trial. Highly effective birth control is defined as those which result in a low failure rate (i.e., less than 1% per year) when used constantly and correctly such as implants, injectables, combined oral contraceptive method, or some intrauterine devices (IUDs), sexual abstinence, or vasectomized partner. Women of non-childbearing potential may be included if surgically sterile (tubal ligation or hysterectomy) or postmenopausal with at least 2 year without spontaneous menses.
• Subjects who are capable to understand the study and the questionnaires, and to comply with the study requirements.

Exclusion Criteria:

• - Pregnant or breastfeeding women
• History of major surgery of the gastrointestinal tract (cholecystectomy and uncomplicated appendectomy are allowed)
• Symptoms predominantly associated with functional dyspepsia or gastro-esophageal reflux disease
• Immunoglobuline E (IgE)-mediated food allergies identified by immunocap blood tests or skin prick testing
• Known underlying organic gastrointestinal disease
• Current or recent use of NSAIDs, proton-pump inhibitors, systemic histamine-receptor antagonists, mast cell stabilizers, corticosteroids, opioids (need to be stopped at least 2 weeks). Use of antibiotics in the past 6 weeks.
• Allergy to Fluorescein, Xylocaine or Propofol
• Known celiac disease
• Following a diet interfering with the study diet in opinion of the investigator