Local immune response to dietary antigens triggered by bacterial infection leads to food-induced abdominal pain

Ingestion of food provides nutrients critical for life/survival, but also represents an important social element in daily life. Up to 20% of the world population, however, develops gastrointestinal symptoms following a meal leading to decreased quality of life, significant morbidity and high medical costs. Although the interest of both the scientific and lay community has increased dramatically with a worldwideintroduction of gluten-free and other diets, the underlying mechanisms leading to food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response leading to dietary antigen-specific IgE antibodies in mice, a mechanism confined to the intestine. Subsequent oral ingestion of the respective dietary antigen results in increased visceral pain via an IgE- and mast cell-dependent mechanism. We show that aberrant painsignaling results from histamine 1 receptor-mediated sensitization of visceral afferents. Moreover, in patients with irritable bowel syndrome (IBS), we also show that local injection of food antigens (gluten,wheat, soy and milk) into the rectosigmoid induced local edema and mast cell activation. Hence, we have unveiled and characterized a novel peripheral