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Despite ongoing efforts, treatment options remain limited. Novel models of food allergy are needed to study response patterns downstream of IgE\u2010crosslinking and evaluate drugs modifying acute events. Here, we report a novel human ex vivo model that displays acute, allergen\u2010specific, IgE\u2010mediated smooth muscle contractions using precision cut intestinal slices (PCIS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PCIS were generated using gut tissue samples from children who underwent clinically indicated surgery. Viability and metabolic activity were assessed from 0 to 24\u2009h. Distribution of relevant cell subsets was confirmed using single nucleus RNA sequencing. PCIS were passively sensitized using plasma from peanut allergic donors or peanut\u2010sensitized non\u2010allergic donors, and exposed to various stimuli including serotonin, histamine, Fc\u025bRI\u2010crosslinker, and food allergens. Smooth muscle contractions and mediator release functioned as readouts. A novel program designed to measure contractions was developed to quantify responses. The ability to demonstrate the impact of antihistamines and immunomodulation from peanut oral immunotherapy (OIT) was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PCIS viability was maintained for 24\u2009h. Cellular distribution confirmed the presence of key cell subsets including mast cells. The video analysis tool reliably quantified responses to different stimulatory conditions. Smooth muscle contractions were allergen\u2010specific and reflected the clinical phenotype of the plasma donor. Tryptase measurement confirmed IgE\u2010dependent mast cell\u2010derived mediator release. Antihistamines suppressed histamine\u2010induced contraction and plasma from successful peanut OIT suppressed peanut\u2010specific PCIS contraction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PCIS represent a novel human tissue\u2010based model to study acute, IgE\u2010mediated food allergy and pharmaceutical impacts on allergic responses in the gut.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15579","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T07:12:55Z","timestamp":1668496375000},"page":"500-511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Precision cut intestinal slices, a novel model of acute food allergic reactions"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4590-1895","authenticated-orcid":false,"given":"Lisa","family":"Hung","sequence":"first","affiliation":[{"name":"Translational Medicine Program, Research Institute Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Immunology, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alper","family":"Celik","sequence":"additional","affiliation":[{"name":"Centre for Computational Medicine, Research Institute Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Yin","sequence":"additional","affiliation":[{"name":"Translational Medicine Program, Research Institute Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Advanced Diagnostics, Toronto General Hospital Research Institute University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Berenjy","sequence":"additional","affiliation":[{"name":"Translational Medicine Program, Research Institute Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1980-161X","authenticated-orcid":false,"given":"Akash","family":"Kothari","sequence":"additional","affiliation":[{"name":"Translational Medicine Program, Research Institute Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Institute of Medical Science, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Obernolte","sequence":"additional","affiliation":[{"name":"Department of Preclinical Pharmacology and In\u2010Vitro Toxicology Fraunhofer Institute for Toxicology and Experimental Medicine  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5320-4232","authenticated-orcid":false,"given":"Julia E. M.","family":"Upton","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, SickKids Food Allergy and Anaphylaxis Program Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Paediatrics, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5266-0372","authenticated-orcid":false,"given":"Katrine","family":"Lindholm B\u00f8gh","sequence":"additional","affiliation":[{"name":"National Food Institute Technical University of Denmark  Kongens Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gino R.","family":"Somers","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Department of Paediatric Laboratory Medicine The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iram","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Department of Paediatric Laboratory Medicine The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Grealish","sequence":"additional","affiliation":[{"name":"Surgical Pathology University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fayez A.","family":"Quereshy","sequence":"additional","affiliation":[{"name":"Surgical Oncology and Minimally Invasive Surgery, Princess Margaret Cancer Centre University Health Network  Toronto Ontario Canada"},{"name":"Department of Surgery, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherina","family":"Sewald","sequence":"additional","affiliation":[{"name":"Department of Preclinical Pharmacology and In\u2010Vitro Toxicology Fraunhofer Institute for Toxicology and Experimental Medicine  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla P. 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