Local immune response to food antigens drives meal-induced abdominal pain
Javier Aguilera‐Lizarraga, Morgane Florens, Maria Francesca Viola, Piyush Jain, Lisse Decraecker, Iris Appeltans, María Cuende‐Estévez, Naomi Fabre, Kim Van Beek, Eluisa Perna, Dafne Balemans, Nathalie Stakenborg, Stavroula Theofanous, Goele Bosmans, Stéphanie Mondelaers, Gianluca Matteoli, Sales Ibiza Martínez, Cintya López-López, Josue Jaramillo-Polanco, Karel Talavera, Yeranddy A. Alpízar, Thorsten B. Feyerabend, Hans‐Reimer Rodewald, Ricard Farré, Frank A. Redegeld, Jiyeon Si, Jeroen Raes, Christine Breynaert, Rik Schrijvers, Cédric Bosteels, Bart N. Lambrecht, Scott D. Boyd, Ramona A. Hoh, Deirdre Cabooter, Maxim Nelis, Patrick Augustijns, Sven Hendrix, Jessica Strid, Raf Bisschops, David E. Reed, Stephen Vanner, Alexandre Denadai‐Souza, Mira M. Wouters, Guy E. Boeckxstaens
Abstract
Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders. In mice, oral tolerance to food antigens can break down after enteric infection, and this leads to food-induced pain resembling irritable bowel syndrome in humans.