These past years, double-blinded placebo controlled food challenges in subjects with irritable bowel syndrome (IBS) reporting sensitivity to gluten have identified a group of individuals without celiac disease (CD) in whom symptoms were clearly aggravated by wheat. Not only did the exposure to wheat trigger intestinal symptoms, but also frequently fatigue and a sensation of foggy mind. Recent studies in mice and sensitive subjects suggest an immune activation by various wheat proteins, with a rapid increase of intestinal mucosal permeability and recruitment of intraepithelial lymphocytes. Moreover, markers of epithelial damage and immune activation are increased in the peripheral blood of wheat-sensitive subjects upon challenge, and decrease under gluten-free diet. Larger studies are needed to better characterize this entity and to distinguish it from food-aggravated IBS and a « forme fruste » of CD.