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Therefore, we aimed to determine effects of fecal luminal factors from IBS patients on the colonic epithelium using colonoids.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Colon\u2010derived organoid monolayers, colonoids, generated from a healthy subject, underwent stimulation with fecal supernatants from healthy subjects and IBS patients with predominant diarrhea, phosphate\u2010buffered saline (PBS), or lipopolysaccharide (LPS). Cytokines in cell cultures and fecal LPS were measured by ELISA and mRNA gene expression of monolayers was analyzed using Qiagen RT<jats:sup>2<\/jats:sup> Profiler PCR Arrays. The fecal microbiota profile was determined by the GA\u2010map<jats:sup>\u2122<\/jats:sup> dysbiosis test and the fecal metabolite profile was analyzed by untargeted liquid chromatography\/mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results<\/jats:title><jats:p>Colonoid monolayers stimulated with fecal supernatants from healthy subjects (<jats:italic>n<\/jats:italic>\u00a0=\u00a07), PBS (<jats:italic>n<\/jats:italic>\u00a0=\u00a04) or LPS (<jats:italic>n<\/jats:italic>\u00a0=\u00a03) presented distinct gene expression profiles, with some overlap (R<jats:sup>2<\/jats:sup>Y\u00a0=\u00a00.70, Q<jats:sup>2\u00a0<\/jats:sup>=\u00a00.43). Addition of fecal supernatants from healthy subjects and IBS patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a09) gave rise to different gene expression profiles of the colonoid monolayers (R<jats:sup>2<\/jats:sup>Y\u00a0=\u00a00.79, Q<jats:sup>2\u00a0<\/jats:sup>=\u00a00.64). Genes (<jats:italic>n<\/jats:italic>\u00a0=\u00a022) related to immune response (CD1D, TLR5) and barrier integrity (CLDN15, DSC2) contributed to the separation. Levels of proinflammatory cytokines in colonoid monolayer cultures were comparable when stimulated with fecal supernatants from either donor types. Fecal microbiota and metabolite profiles, but not LPS content, differed between the study groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Fecal luminal factors from IBS patients induce a distinct colonic epithelial gene expression, potentially reflecting the disease pathophysiology. The culture of colonoids from healthy subjects with fecal supernatants from IBS patients may facilitate the exploration of IBS related intestinal micro\u2010environmental and barrier interactions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14390","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T13:56:10Z","timestamp":1651240570000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Fecal luminal factors from patients with irritable bowel syndrome induce distinct gene expression of colonoids"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0632-7552","authenticated-orcid":false,"given":"Cristina","family":"Iribarren","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Institute of Biomedicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Molecular and Clinical Medicine Institute of Medicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1353-3781","authenticated-orcid":false,"given":"Sofia","family":"Nordlander","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Institute of Biomedicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Molecular and Clinical Medicine Institute of Medicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-1772","authenticated-orcid":false,"given":"Johanna","family":"Sundin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Institute of Biomedicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Isaksson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Institute of Biomedicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Savolainen","sequence":"additional","affiliation":[{"name":"Chalmers Mass Spectrometry Infrastructure Department of Biology and Biological Engineering Chalmers University of Technology  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"T\u00f6rnblom","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Medicine Institute of Medicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria K.","family":"Magnusson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Institute of Biomedicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Simr\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Medicine Institute of Medicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"},{"name":"Center for Functional GI and Motility Disorders University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8142-2106","authenticated-orcid":false,"given":"Lena","family":"\u00d6hman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Institute of Biomedicine Sahlgrenska Academy University of Gothenburg  Gothenburg 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