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Local immune response to food antigens drives meal-induced abdominal pain
Open accessAbstract
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.
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“In a mouse model, bacterial infection led to an increase in intestinal permeability, which appeared to allow previously tolerated food antigens to activate a localised host immune response in the gastrointestinal tract, via IgE, leading to histamine release, altered motility and visceral hypersensitivity.73”
From British Society of Gastroenterology guidelines on the management of irritable bowel syndrome (2021) · cites this paper as [73]
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Zi-wen, Z. H. O. U., Liu, L., Fu, J., Yan, H., Sheng, Y. J., & Zhang, Z. (2026) · Medicine · doi:10.1097/md.0000000000049899
Metadata
- Authors
- Aguilera-Lizarraga, J., Florens, M. V., Viola, M. F., Jain, P., Decraecker, L., Appeltans, I., Cuende-Estevez, M., Fabre, N., Van Beek, K., Perna, E., Balemans, D., Stakenborg, N., Theofanous, S., Bosmans, G., Mondelaers, S. U., Matteoli, G., Ibiza Martínez, S., Lopez-Lopez, C., Jaramillo-Polanco, J., Talavera, K., Alpizar, Y. A., Feyerabend, T. B., Rodewald, H.-R., Farre, R., Redegeld, F. A., Si, J., Raes, J., Breynaert, C., Schrijvers, R., Bosteels, C., Lambrecht, B. N., Boyd, S. D., Hoh, R. A., Cabooter, D., Nelis, M., Augustijns, P., Hendrix, S., Strid, J., Bisschops, R., Reed, D. E., Vanner, S. J., Denadai-Souza, A., Wouters, M. M., & Boeckxstaens, G. E.
- Affiliations
- KU Leuven (BE)
- Queen's University (CA)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- Hasselt University (BE)
- German Cancer Research Center (DE)
- Utrecht University (NL)
- Rega Institute for Medical Research (BE)
- Ghent University (BE)
- Erasmus MC (NL)
- Stanford Medicine (US)
- MSH Medical School Hamburg – University of Applied Sciences and Medical University (DE)
- Imperial College London (GB)
- Corresponding author
- Boeckxstaens, Guy E.
- ORCID
- Aguilera-Lizarraga, Javier
- Florens, Morgane V.
- Viola, Maria Francesca
- Jain, Piyush
- Decraecker, Lisse
- Fabre, Naomi
- Perna, Eluisa
- Stakenborg, Nathalie
- Theofanous, Stavroula
- Bosmans, Goele
- Matteoli, Gianluca
- Jaramillo-Polanco, Josue
- Talavera, Karel
- Alpizar, Yeranddy A.
- Feyerabend, Thorsten B.
- Rodewald, Hans-Reimer
- Farre, Ricard
- Redegeld, Frank A.
- Si, Jiyeon
- Raes, Jeroen
- Breynaert, Christine
- Schrijvers, Rik
- Bosteels, Cédric
- Lambrecht, Bart N.
- Boyd, Scott D.
- Hoh, Ramona A.
- Cabooter, Deirdre
- Augustijns, Patrick
- Hendrix, Sven
- Strid, Jessica
- Bisschops, Raf
- Reed, David E.
- Vanner, Stephen J.
- Denadai-Souza, Alexandre
- Wouters, Mira M.
- Boeckxstaens, Guy E.
- Venue
- Nature
- Published
- 2021-01-13
- Volume
- 590
- Issue
- 7844
- Pages
- 151-156
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7610810
- OpenAlex
- W3120299325
- Cited by
- 311
- References
- 55
- Citations by year
- 2026: 46 · 2025: 55 · 2024: 58 · 2023: 52 · 2022: 56 · 2021: 44
- FWCI
- 48.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- Document Server@UHasselt (UHasselt) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Lirias (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- Wellcome Trust (215488/Z/19/Z)
- Fonds Wetenschappelijk Onderzoek (11C2219N, 1110019 N, G092915, 12V3619N, 1248513 N, 12H8220N, 12R5219N, FWO G.0929.15, 12X9820N, G0A9516N, 1127415N)
- KU Leuven (GOA 14.011, GOA 14.011, C14/18/086, C14/18/086)
- Crohn's and Colitis Canada (625742)
- National Institutes of Health (LSM880, NIAID-R01)
- Genentech
- National Institute of Allergy and Infectious Diseases (R01AI025567, R01AI125567)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Keywords
- irritable bowel syndrome, food antigens, IgE antibodies, mast cells, histamine H1 receptor, visceral pain, oral tolerance, gastrointestinal infections, bacterial toxins, gluten, wheat, soybean, milk, peripheral immune response
- MeSH terms
- Adult, Allergens, Animals, Diarrhea, Enterobacteriaceae Infections, Female, Food, Food Hypersensitivity, Glutens, Humans, Immunoglobulin E, Intestinal Mucosa, Intestines, Male, Mast Cells, Mice, Inbred BALB C, Middle Aged, Milk, Ovalbumin, Quality of Life, Receptors, Histamine H1, Triticum, Abdominal Pain, Soybean Proteins, Irritable Bowel Syndrome, Citrobacter rodentium, Mice
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