The aim of our study will be to establish in how many subjects with gastrointestinal symptoms and previous diagnosis of irritable bowel syndrome (IBS), the clinical picture is attributable to non celiac gluten sensitivity (NCGS) or fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) intolerance. For this purpose, all subjects with IBS will take a low FODMAPs diet, which implies the absence of cereals and consequently of gluten, and those presenting symptom improvement during this dietary treatment, will be exposed to a double-blind gluten or placebo challenge, to make a diagnosis of NCGS.

Study design:

For this study, patients with diagnosis of IBS performed by Rome IV criteria and followed as outpatients at the Clinical Nutrition Clinic of "Petrucciani" Nursing Home of Lecce (LE), Italy, will be enrolled.

At baseline, the enrolled subjects will follow a balanced normal-caloric low-FODMAP and gluten-free diet for a period of 4 weeks. At the end of the 4 weeks patients who did not experience an improvement in symptoms will be considered "non-responders" and discontinue the clinical trial. Only those subjects who had showed a significant improvement in symptoms, will be enrolled for the phase 2 of the study that includes a challenge with gluten or with placebo, as described by the Salerno criteria.

Inclusion Criteria:

• a gluten-containing diet for at least six months before enrollment
• anti-transglutaminase antibodies (IgA and IgG) absence
• normal serum IgA levels
• prick and specific IgE tests for wheat allergy negative

Exclusion Criteria:

• celiac disease
• wheat allergy
• chronic intestinal inflammatory diseases
• psychiatric disorders
• major abdominal surgery (in particular intestinal resections)
• diabetes mellitus
• previous anaphylactic episodes
• gluten-free diet in the previous six months
• pregnant or lactating women.