{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T10:21:40Z","timestamp":1793701300961,"version":"4.5.1"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Gut\u2010liver axis has been implicated in the pathophysiology of cirrhosis due to metabolic dysfunction\u2010associated steatotic liver disease (MASLD), an in\u00a0vitro model for studying epithelial gut dysfunction in MASLD is lacking. In this study, we aimed to characterise intestinal organoids derived from subjects with MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Intestinal organoids were obtained from duodenal samples of individuals with non\u2010fibrotic MASLD and with MASLD\u2010cirrhosis. After 7 to 10\u2009days of culture, RNA extraction, transcriptomic analysis and real\u2010time PCR were performed. Energetic and redox\n                      <jats:italic>status<\/jats:italic>\n                      of organoids were assessed by chromatographic analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Microarray analysis showed approximately 600 dysregulated transcripts in organoids isolated from patients with MASLD\u2010cirrhosis compared to non\u2010fibrotic MASLD. Bioinformatic analysis indicated that dysregulated transcripts were involved in pathways related to regeneration and pluripotency of stem cells and regulating mitochondrial metabolism and hypoxia. Overall, chromatographic analysis demonstrated that energetic\n                      <jats:italic>status<\/jats:italic>\n                      was remarkably impaired in both differentiated and undifferentiated organoids from cirrhotic patients compared to steatotic subjects. In either undifferentiated or differentiated organoids from cirrhotic subjects, the triphosphate sum, the ATP\/ADP and NAD\n                      <jats:sup>+<\/jats:sup>\n                      \/NADH ratios were lower in MASLD\u2010cirrhosis, indicating a decline in the phosphorylating capacity and a mitochondrial derangement of duodenal cells. In addition, we found lower levels of reduced glutathione, NADPH and UDP\u2010glucuronic acid in undifferentiated and differentiated cells from cirrhotics indicating impairment of antioxidant defence and of response to xenobiotics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study provides a comprehensive view of intestinal epithelial dysfunction in MASLD\u2010cirrhosis, characterised by a cluster of regenerative and metabolic disturbances.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70331","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T06:39:23Z","timestamp":1757572763000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impairment of Regenerative and Metabolic Pathways in Intestinal Organoids From Patients With MASLD\u2010Cirrhosis"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6593-8823","authenticated-orcid":false,"given":"Agnese","family":"Filippello","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery \u2018Kore\u2019 University of Enna  Enna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4483-3365","authenticated-orcid":false,"given":"Alessandra","family":"Scamporrino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Di Mauro","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery \u2018Kore\u2019 University of Enna  Enna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela 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