{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:49:49Z","timestamp":1789469389209,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T00:00:00Z","timestamp":1631404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Eosinophilic esophagitis (EoE) is a food allergen driven disease that is accompanied by interleukin (IL) 13 overexpression and esophageal barrier dysfunction allowing transepithelial food allergen permeation. Nutraceuticals, such as short\u2010chain fatty acids (SCFAs) that restore barrier function and increase immune fitness may be a promising tool in the management of EoE. Here, we investigated the effects of the SCFAs acetate, propionate, and butyrate on an IL\u201013\u2010compromised human esophageal epithelial barrier, including the mechanisms involved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An air\u2010liquid interface culture model of differentiated human EPC2\u2010hTERT (EPC2) was used to study whether SCFAs could restore barrier function after IL\u201013\u2010induced impairment. Esophageal epithelial barrier function was monitored by transepithelial electrical resistance (TEER) and FITC\u2010dextran paracellular flux, and was further examined by qPCR and immunohistochemical analysis. G protein\u2010coupled receptor (GPR) GPR41, GPR43, GPR109a, or histone deacetylase (HDAC) (ant)agonists were used to assess mechanisms of action of SCFAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IL\u201013\u00a0stimulation decreased TEER and increased FITC flux, which was counteracted by butyrate and propionate, but not acetate treatment. Barrier proteins <jats:italic>FLG<\/jats:italic> and <jats:italic>DSG1<\/jats:italic>\u00a0mRNA expression was upregulated following butyrate and propionate treatment, whereas expression of eosinophil chemoattractant <jats:italic>CCL26<\/jats:italic> and protease <jats:italic>CAPN14<\/jats:italic> was downregulated. Similarly, butyrate and propionate restored FLG and DSG1 protein expression. Similar effects were observed with an HDAC antagonist but not with GPR agonists.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Nutraceuticals butyrate and propionate restore the barrier function of esophageal epithelial cells after an inflammatory insult and may be of therapeutic benefit in the management of EoE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15069","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T08:25:51Z","timestamp":1630311951000},"page":"1510-1521","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Butyrate and propionate restore interleukin 13\u2010compromised esophageal epithelial barrier function"],"prefix":"10.1111","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1366-6034","authenticated-orcid":false,"given":"Mirelle T.A.","family":"Kleuskens","sequence":"first","affiliation":[{"name":"Division of Pharmacology Utrecht Institute for Pharmaceutical Sciences Faculty of Science Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Haasnoot","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology &amp; Hepatology Amsterdam UMC, location AMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart M.","family":"Herpers","sequence":"additional","affiliation":[{"name":"Division of Pharmacology Utrecht Institute for Pharmaceutical Sciences Faculty of Science Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen T. 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