{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:21:22Z","timestamp":1790392882480,"version":"4.1.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2018,2,19]],"date-time":"2018-02-19T00:00:00Z","timestamp":1518998400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,2,19]],"date-time":"2018-02-19T00:00:00Z","timestamp":1518998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>\n                    Portal hypertension (PH) drives most of the clinical complications in chronic liver diseases. However, its progression in nonalcoholic steatohepatitis (NASH) and its association with the intestinal microbiota (IM) have been scarcely studied. Our aim was to investigate the role of the IM in the mechanisms leading to PH in early NASH. The experimental design was divided in two stages. In stage 1, Sprague\u2010Dawley rats were fed for 8 weeks a high\u2010fat, high\u2010glucose\/fructose diet (HFGFD) or a control diet\/water (CD). Representative rats were selected as IM donors for stage 2. In stage 2, additional HFGFD and CD rats underwent intestinal decontamination, followed by IM transplantation with feces from opposite\u2010diet donors (heterologous transplant) or autologous fecal transplant (as controls), generating four groups: CD\u2010autotransplanted, CD\u2010transplanted, HFGFD\u2010autotransplanted, HFGFD\u2010transplanted. After IM transplantation, the original diet was maintained for 12\u201014 days until death. HFGFD rats developed obesity, insulin resistance, NASH without fibrosis but with PH, intrahepatic endothelial dysfunction, and IM dysbiosis. In HFGFD rats, transplantation with feces from CD donors caused a significant reduction of PH to levels comparable to CD without significant changes in NASH histology. The reduction in PH was due to a 31% decrease of intrahepatic vascular resistance compared to the HFGFD\u2010autotransplanted group (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u20090.05). This effect occurs through restoration of the sensitivity to insulin of the hepatic protein kinase B\u2013dependent endothelial nitric oxide synthase signaling pathway.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : The IM exerts a direct influence in the development of PH in rats with diet\u2010induced NASH and dysbiosis; PH, insulin resistance, and endothelial dysfunction revert when a healthy IM is restored. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2018;67:1485\u20101498)\n                  <\/jats:p>","DOI":"10.1002\/hep.29646","type":"journal-article","created":{"date-parts":[[2017,11,7]],"date-time":"2017-11-07T17:42:37Z","timestamp":1510076557000},"page":"1485-1498","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":120,"title":["Restoration of a healthy intestinal microbiota normalizes portal hypertension in a rat model of nonalcoholic steatohepatitis"],"prefix":"10.1097","volume":"67","author":[{"given":"Teresa","family":"Garc\u00eda\u2010Lezana","sequence":"first","affiliation":[{"name":"Liver Unit, Department of Internal Medicine,Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron, Universitat Aut\u00f2noma de Barcelona,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imma","family":"Raurell","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Internal Medicine,Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron, Universitat Aut\u00f2noma de Barcelona,Barcelona,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III,Madrid,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miren","family":"Bravo","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Internal Medicine,Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron, Universitat Aut\u00f2noma de Barcelona,Barcelona,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III,Madrid,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Torres\u2010Arauz","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Internal Medicine,Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron, Universitat Aut\u00f2noma de Barcelona,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"Salcedo","sequence":"additional","affiliation":[{"name":"Department of Pathology,Hospital Universitari Vall d'Hebron"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Santiago","sequence":"additional","affiliation":[{"name":"Digestive System Research Unit, Institut de Recerca Vall d'Hebron,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreu","family":"Schoenenberger","sequence":"additional","affiliation":[{"name":"Digestive System Research Unit, Institut de Recerca Vall d'Hebron,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaysavanh","family":"Manichanh","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III,Madrid,Spain"},{"name":"Digestive System Research Unit, Institut de Recerca Vall d'Hebron,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0831-8422","authenticated-orcid":false,"given":"Joan","family":"Genesc\u00e0","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Internal Medicine,Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron, Universitat Aut\u00f2noma de Barcelona,Barcelona,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III,Madrid,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Martell","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Internal Medicine,Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron, Universitat Aut\u00f2noma de Barcelona,Barcelona,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III,Madrid,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Augustin","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Internal Medicine,Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron, Universitat Aut\u00f2noma de Barcelona,Barcelona,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Instituto de Salud Carlos 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