{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361137044862113152.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1152/ajpgi.00267.2012"}},{"identifier":{"@type":"URI","@value":"https://www.physiology.org/doi/pdf/10.1152/ajpgi.00267.2012"}}],"dc:title":[{"@value":"A novel mechanism for gut barrier dysfunction by dietary fat: epithelial disruption by hydrophobic bile acids"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p> Impairment of gut barrier is associated with a fat-rich diet, but mechanisms are unknown. We have earlier shown that dietary fat modifies fecal bile acids in mice, decreasing the proportion of ursodeoxycholic acid (UDCA) vs. deoxycholic acid (DCA). To clarify the potential role of bile acids in fat-induced barrier dysfunction, we here investigated how physiological concentrations of DCA and UDCA affect barrier function in mouse intestinal tissue. Bile acid experiments were conducted in vitro in Ussing chambers using 4- and 20-kDa FITC-labeled dextrans. Epithelial integrity and inflammation were assayed by histology and Western blot analysis for cyclooxygenase-2. LPS was studied in DCA-induced barrier dysfunction. Finally, we investigated in a 10-wk in vivo feeding trial in mice the barrier-disrupting effect of a diet containing 0.1% DCA. DCA disrupted epithelial integrity dose dependently at 1–3 mM, which correspond to physiological concentrations on a high-fat diet. Low-fat diet-related concentrations of DCA had no effect. In vivo, the DCA-containing diet increased intestinal permeability 1.5-fold compared with control ( P = 0.016). Hematoxylin-eosin staining showed a clear disruption of the epithelial barrier by 3 mM DCA in vitro. A short-term treatment by DCA did not increase cyclooxygenase-2 content in colon preparations. UDCA did not affect barrier function itself, but it ameliorated DCA-induced barrier disruption at a 0.6 mM concentration. LPS had no significant effect on barrier function at 0.5–4.5 μg/ml concentrations. We suggest a novel mechanism for barrier dysfunction on a high-fat diet involving the effect of hydrophobic luminal bile acids. </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381137044862113153","@type":"Researcher","foaf:name":[{"@value":"Lotta K. Stenman"}],"jpcoar:affiliationName":[{"@value":"Institute of Biomedicine, Pharmacology, Medical Nutrition Physiology, University of Helsinki, Helsinki, Finland; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044862113154","@type":"Researcher","foaf:name":[{"@value":"Reetta Holma"}],"jpcoar:affiliationName":[{"@value":"Institute of Biomedicine, Pharmacology, Medical Nutrition Physiology, University of Helsinki, Helsinki, Finland; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044862113152","@type":"Researcher","foaf:name":[{"@value":"Ariane Eggert"}],"jpcoar:affiliationName":[{"@value":"Institute of Water and Wetland Research, Animal Physiology, Radboud University Nijmegen, Nijmegen, The Netherlands"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044862113155","@type":"Researcher","foaf:name":[{"@value":"Riitta Korpela"}],"jpcoar:affiliationName":[{"@value":"Institute of Biomedicine, Pharmacology, Medical Nutrition Physiology, University of Helsinki, Helsinki, Finland; and"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"01931857"},{"@type":"EISSN","@value":"15221547"}],"prism:publicationName":[{"@value":"American Journal of Physiology-Gastrointestinal and Liver Physiology"}],"dc:publisher":[{"@value":"American Physiological Society"}],"prism:publicationDate":"2013-02-01","prism:volume":"304","prism:number":"3","prism:startingPage":"G227","prism:endingPage":"G234"},"reviewed":"false","url":[{"@id":"https://www.physiology.org/doi/pdf/10.1152/ajpgi.00267.2012"}],"createdAt":"2012-11-30","modifiedAt":"2019-09-09","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050585658871497216","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Impact of Vancomycin Treatment and Gut Microbiota on Bile Acid Metabolism and the Development of Non-Alcoholic Steatohepatitis in Mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360294643760590848","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"12α-Hydroxylated bile acid enhances accumulation of adiponectin and immunoglobulin A in the rat ileum"}]},{"@id":"https://cir.nii.ac.jp/crid/1360576118736916992","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Dietary supplementation with okara and Bacillus coagulans lilac-01 improves hepatic lipid accumulation induced by cholic acids in rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588380127201152","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Impacts of liver macrophages, gut microbiota, and bile acid metabolism on the differences in iHFC diet-induced MASH progression between TSNO and TSOD mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588381052817408","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Antibiotic effects on gut microbiota modulate diet‐induced metabolic dysfunction‐associated steatohepatitis development in C57BL/6 mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846641718647040","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865814753615104","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Combined, elobixibat, and colestyramine reduced cholesterol toxicity in a mouse model of metabolic dysfunction-associated steatotic liver disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865815490542976","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Deoxycholic acid enhancement of lymphocyte migration through direct interaction with the intestinal vascular endothelium"}]},{"@id":"https://cir.nii.ac.jp/crid/1361412889584929536","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Role of the Gut–Liver Axis in Liver Inflammation, Fibrosis, and Cancer: A Special Focus on the Gut Microbiota Relationship"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1152/ajpgi.00267.2012"},{"@type":"CROSSREF","@value":"10.1038/ctg.2016.44_references_DOI_ZSw0283hsnoKs9lLdOuUZmuCXzl"},{"@type":"CROSSREF","@value":"10.1038/s41598-021-92302-z_references_DOI_ZSw0283hsnoKs9lLdOuUZmuCXzl"},{"@type":"CROSSREF","@value":"10.3390/ijms24044050_references_DOI_ZSw0283hsnoKs9lLdOuUZmuCXzl"},{"@type":"CROSSREF","@value":"10.1016/j.jff.2022.104991_references_DOI_ZSw0283hsnoKs9lLdOuUZmuCXzl"},{"@type":"CROSSREF","@value":"10.1007/s00011-024-01884-7_references_DOI_ZSw0283hsnoKs9lLdOuUZmuCXzl"},{"@type":"CROSSREF","@value":"10.1111/gtc.13134_references_DOI_ZSw0283hsnoKs9lLdOuUZmuCXzl"},{"@type":"CROSSREF","@value":"10.1097/hc9.0000000000000285_references_DOI_ZSw0283hsnoKs9lLdOuUZmuCXzl"},{"@type":"CROSSREF","@value":"10.1111/jgh.15509_references_DOI_ZSw0283hsnoKs9lLdOuUZmuCXzl"},{"@type":"CROSSREF","@value":"10.1002/hep4.1331_references_DOI_ZSw0283hsnoKs9lLdOuUZmuCXzl"}]}