Local immune response to food antigens drives meal-induced abdominal pain

Javier Aguilera-Lizarraga, Morgane V. Florens, Maria Francesca Viola, Piyush Jain, Lisse Decraecker, Iris Appeltans, Maria Cuende-Estevez, Naomi Fabre, Kim Van Beek, Eluisa Perna, Dafne Balemans, Nathalie Stakenborg, Stavroula Theofanous, Goele Bosmans, Stéphanie U. Mondelaers, Gianluca Matteoli, Sales Ibiza Martínez, Cintya Lopez-Lopez, Josue Jaramillo-Polanco, Karel TalaveraYeranddy A. Alpizar, Thorsten B. Feyerabend, Hans Reimer Rodewald, Ricard Farre, 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 J. Vanner, Alexandre Denadai-Souza, Mira M. Wouters, Guy E. Boeckxstaens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

159 Citations (Scopus)
37 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)151-156
Number of pages6
Issue number7844
Publication statusPublished - 4 Feb 2021

Bibliographical note

Funding Information:
Acknowledgements We thank I. Croux and R. De Keyser for technical assistance; L. Beullens, A. W. Essilfie, H. Willekens and H. Volkaerts for nursing assistance in the studies involving human subjects; M. Rasulova for assistance with ELISpot plate read-out; and the Cell and Tissue Imaging Cluster for the use of the NIKON inverted TillVision microscope, epifluorescence microscope BX 41 Olympus and Zeiss LSM880—Airyscan—and Zeiss LSM 780—SP Mai Tai HP DS—confocal microscopes (Cell and Tissue Imaging Cluster, CIC, supported by Hercules AKUL/15/37_GOH1816N and FWO G.0929.15 to P. Vanden Berghe). Flow cytometry was done at the FACS Core facility (KU Leuven) and we thank P. Andrée Penttila and P. Kumar for technical assistance. We thank the National Reference Centre (NRC) for S. aureus of Université Libre de Bruxelles (ULB) for SAgs-positive S. aureus strains; and Genentech for the IgG2a anti-CD20 antibody and its isotype control. M.V.F., M.F.V. and D.B. were supported by FWO PhD fellowships (1110019N, 11C2219N and 1127415N, respectively). C. Breynaert is supported by the Clinical Research Fund, University Hospitals, Leuven. J.A.-L., M.M.W., P.J., N.S. and Y.A.A. were supported by FWO postdoctoral fellowships (12X9820N, 1248513N, 12R5219N, 12V3619N and 12H8220N, respectively). During this project J.A.-L. was also previously supported by an FWO PhD fellowship (11Y2116N). T.B.F. and H.-R.R. were supported by SFB-TRR156-A07. S.D.B. is supported by NIH grant NIAID R01 AI125567 and an endowment from the Crown Family Foundation. G.E.B. was funded by a KU Leuven university grant (Global Opportunities for Associations GOA 14.011, C14/18/086) and an FWO grant (G0A9516N).

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© 2021, The Author(s), under exclusive licence to Springer Nature Limited.


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