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A link between stress and intestinal permeability has been shown in animal models as well as in human small intestine, but stress effects on the human colorectal mucosal barrier has not been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the potential effects of acute psychological stress on colorectal mucosal barrier function and to explore stress\u2010induced molecular events in the rectal mucosa under healthy conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Endoscopic biopsies were taken from the rectosigmoid region of healthy volunteers, who had been subjected to dichotomous listening stress and after a control session, respectively. Paracellular and transcellular permeability were assessed in modified Ussing chambers. RNA expression (microarray technology confirmed by quantitative real\u2010time polymerase chain reaction) and biological pathway analysis were used to investigate the local mucosal response to acute stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Dichotomous listening stress induced a subjective and objective stress response, and significantly increased paracellular but not transcellular permeability. We also identified a stress\u2010induced reduction in RNA expression of genes related to immune cell activation and maturation (<jats:italic>CR2<\/jats:italic>, <jats:italic>CD20<\/jats:italic>, <jats:italic>TCLA1<\/jats:italic>, <jats:italic>BANK1<\/jats:italic>, <jats:italic>CD22<\/jats:italic>, <jats:italic>FDCSP<\/jats:italic>), signaling molecules of homing of immune cells to the gut (chemokines: <jats:italic>CCL21<\/jats:italic>, <jats:italic>CXCL13<\/jats:italic>, and <jats:italic>CCL19<\/jats:italic>, and receptors: <jats:italic>CCR7<\/jats:italic>, <jats:italic>CXCR5<\/jats:italic>), and innate immunity (<jats:italic>DUOX2<\/jats:italic>). Eight of the 10 top down\u2010regulated genes are directly involved in B cell activation, signaling and migration. The systemic stress response correlated positively with paracellular permeability and negatively with <jats:italic>DUOX2<\/jats:italic> expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Dichotomous listening stress increases paracellular permeability and modulates immune cell activity in the rectal mucosa. Further studies are warranted to identify the primary mechanisms of stress\u2010mediated reduction of mucosal defensive activity and barrier dysfunction, and their potential implications for gastrointestinal disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ueg2.12329","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T13:46:40Z","timestamp":1667224000000},"page":"31-41","source":"Crossref","is-referenced-by-count":11,"title":["Acute psychological stress increases paracellular permeability and modulates immune activity in rectal mucosa of healthy volunteers"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-7303","authenticated-orcid":false,"given":"Linda","family":"Gerdin","sequence":"first","affiliation":[{"name":"Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Department of Surgery Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Surgical Clinic of J\u00f6nk\u00f6ping County  J\u00f6nk\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Gonz\u00e1lez\u2010Castro","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Mucosal Immunology Digestive Diseases Research Unit Vall d'Hebron Institut de Recerca Hospital Universitari Vall d'Hebron &amp; Facultat de Medicina Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann\u2010Charlott","family":"Ericson","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Department of Surgery Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"Persborn","sequence":"additional","affiliation":[{"name":"Surgical Clinic of J\u00f6nk\u00f6ping County  J\u00f6nk\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Neuro\u2010immuno\u2010gastroenterology Digestive Diseases Research Unit Vall d'Hebron Institut de Recerca Hospital Universitari Vall d'Hebron &amp; Facultat de Medicina Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna A.","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Department of Surgery Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Department of Gastroenterology Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6820-0215","authenticated-orcid":false,"given":"\u00c5sa V.","family":"Keita","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Department of Surgery Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Vicario","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Mucosal Immunology Digestive Diseases Research Unit Vall d'Hebron Institut de Recerca Hospital Universitari Vall d'Hebron &amp; Facultat de Medicina Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)  Barcelona Spain"},{"name":"Department of Gastrointestinal Health Nestl\u00e9 Institute of Health Sciences Nestl\u00e9 Research, Soci\u00e9t\u00e9 des Produits Nestl\u00e9 S.A.  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