{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:28:13Z","timestamp":1788996493741,"version":"build-2803163510"},"reference-count":68,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The epithelial barrier theory has been proposed to link the onset of many chronic inflammatory diseases to the damaged epithelial barrier induced by numerous environmental factors, including food emulsifiers. This study aimed to investigate the effects of food emulsifiers kappa\u2010, iota\u2010 and lambda\u2010carrageenan on intestinal epithelial barrier integrity and the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The cytotoxicity and apoptosis of carrageenans were determined using Hoechst\/propidium iodide staining and FITC annexin V\/propidium iodide staining, respectively. The gut\u2010on\u2010a\u2010chip was established and transepithelial electrical resistance measurement, paracellular flux assay, immunofluorescence staining of tight junction proteins, RNA\u2010sequencing and targeted proteomics were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Kappa\u2010, iota\u2010 and lambda\u2010carrageenans induced dose\u2010dependent cytotoxicity, with lambda\u2010carrageenan showing a more severe cytotoxic effect in relatively lower doses. All three carrageenans elicited a dose\u2010 and time\u2010dependent decrease of gut epithelial barrier strength, a significant increase in the paracellular flux and irregular and heterogeneous staining of occludin and ZO\u20101 compared to the untreated group, suggesting the disruption of the intestinal epithelial barrier integrity. Transcriptomics data revealed that iota\u2010 and lambda\u2010carrageenan induced more severe pro\u2010inflammatory responses, which were associated with the upregulation of genes involved in TNF signalling, IL\u201017 signalling cellular response to chemokines, cholesterol metabolism and NF\u2010kappa B signalling pathways. Targeted proteomics data from exposed gut\u2010on\u2010a\u2010chips indicated an upregulation of inflammation\u2010 and immune response\u2010related proteins for all three carrageenans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present study provides direct evidence for the detrimental effects of kappa\u2010, iota\u2010 and lambda\u2010carrageenans on gut epithelial cell activation and barrier integrity. The underlying mechanism of epithelial barrier disruption was largely attributed to the activation of innate immune responses by carrageenans, resulting in a pro\u2010inflammatory response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cea.70266","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T02:48:11Z","timestamp":1775530091000},"page":"769-783","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of Common Food Additives Kappa\u2010, Iota\u2010 and Lambda\u2010Carrageenans on Intestinal Epithelial Cell Activation and Barrier Disruption"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9936-6907","authenticated-orcid":false,"given":"Na","family":"Sun","sequence":"first","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"},{"name":"SKL of Marine Food Processing &amp; Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology Dalian Polytechnic University  Dalian P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yagiz","family":"Pat","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6985-9436","authenticated-orcid":false,"given":"Huseyn","family":"Babayev","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sena","family":"Ardicli","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"},{"name":"Department of Genetics, Faculty of Veterinary Medicine Bursa Uludag University  Bursa Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Ogulur","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5488-062X","authenticated-orcid":false,"given":"Xianting","family":"Bu","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manru","family":"Li","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Jia","sequence":"additional","affiliation":[{"name":"SKL of Marine Food Processing &amp; Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology Dalian Polytechnic University  Dalian P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"R\u00fcckert","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja","family":"Dhir","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2146-2955","authenticated-orcid":false,"given":"Kari C.","family":"Nadeau","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, T.H. Chan School of Public Health Harvard University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubeccel","family":"Akdis","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cezmi A.","family":"Akdis","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duygu","family":"Yazici","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00538-7"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101846"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.9b06379"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.11.010"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.16318"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cod.13959"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11051111"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41430-022-01225-z"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2020.12.018"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ypmed.2019.05.004"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14232"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.11.006"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15825"},{"key":"e_1_2_11_15_1","unstructured":"\u201cEN Evaluation of Certain Food Additives \u201d2015."},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/1541-4337.12790"},{"key":"e_1_2_11_17_1","article-title":"Re\u2010Evaluation of Carrageenan (E 407) and Processed Eucheuma Seaweed (E 407a) as Food Additives","volume":"16","author":"Additives EPoF, Food NSat","year":"2018","journal-title":"EFSA Journal"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7FO01721A"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7FO01721A"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13103402"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2022.120374"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2013.1726"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2012.04.012"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/397642"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2017.07.904"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8634865"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0LC00770F"},{"key":"e_1_2_11_28_1","article-title":"An Automated Differential Nuclear Staining Assay for Accurate Determination of Mitocan Cytotoxicity","volume":"159","author":"Pei J.","year":"2020","journal-title":"JoVE (Journal of Visualized Experiments)"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-024-00893-5"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuaa038"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.11.030"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2023.113369"},{"key":"e_1_2_11_33_1","unstructured":"L.PereiraandL.Al \u201cCarrageenans \u2010 Sources and Extraction Methods Molecular Structure Bioactive Properties and Health Effects \u201d2016."},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10811-007-9252-x"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods14040635"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1967.tb08023.x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2021.118830"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105940"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-006-0377-7"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1768-322X.1986.tb00471.x"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(84)90297-8"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929866524666170724113452"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.01.002"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4682rev"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2012.02.031"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.104"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2024828118"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00380.2006"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.2174\/0127722708303188240708071523"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2009.07.002"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0190-7"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R114.583658"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)02064-5"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.12.7199"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-016-0458-4"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.021"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.4070\/kcj.2021.0252"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207619"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0701-2"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.23034"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2005.00218.x"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-017-0566-5"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00030.2015"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.05.021"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06918-3"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI124884"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tifs.2020.11.015"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2019.108906"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.16343"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.70266","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cea.70266","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.70266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:44:46Z","timestamp":1783014286000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.70266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,6]]},"references-count":68,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/cea.70266"],"URL":"https:\/\/doi.org\/10.1111\/cea.70266","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,6]]},"assertion":[{"value":"2025-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}