{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:07:22Z","timestamp":1789189642651,"version":"build-2803163510"},"reference-count":107,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["PNRR-MAD-2022-12376791"],"award-info":[{"award-number":["PNRR-MAD-2022-12376791"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PNRR-MAD-2022-12376791"],"award-info":[{"award-number":["PNRR-MAD-2022-12376791"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Short bowel syndrome is a rare and clinically heterogeneous condition resulting from extensive intestinal resections or functional impairment, leading to malabsorption, fluid and electrolyte losses, and potential progression to intestinal failure requiring long-term parenteral nutrition. The long-term outcome of SBS is largely determined by intestinal adaptation, a progressive physiological response involving epithelial remodeling, intestinal stem cell expansion, lineage-specific proliferation, vascular remodeling, and the activity of trophic mediators\u2014most notably glucagon-like peptide-2 (GLP-2)\u2014whose clinical relevance is exemplified by teduglutide. Despite significant therapeutic advances, the mechanisms underlying adaptation remain incompletely understood, and preclinical models are essential tools for addressing this gap. In vitro systems\u2014including Caco-2 epithelial cultures, intestinal organoids and enteroids, and tissue-engineered intestinal constructs\u2014enable pathway-specific mechanistic investigation and hold promise as regenerative platforms. Murine surgical models of small bowel resection and ileocecal resection provide an integrated in vivo context for dissecting cellular and molecular mechanisms of adaptation. Large animal models, particularly minipig platforms, offer anatomical and physiological proximity to humans required for translational and therapeutic evaluation. In this narrative review, we provide an updated overview of these preclinical systems, critically examining their respective strengths, limitations, and translational relevance to advance the understanding of intestinal adaptation and inform the development of more effective therapeutic strategies for SBS (graphical abstract).<\/jats:p>","DOI":"10.3390\/cells15181642","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:04:57Z","timestamp":1789045497000},"page":"1642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biological Insights into Intestinal Adaptation from Preclinical Models of Short Bowel Syndrome"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8184-8559","authenticated-orcid":false,"given":"Cesare","family":"Pane","sequence":"first","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0935-8853","authenticated-orcid":false,"given":"Pierluigi","family":"Puca","sequence":"additional","affiliation":[{"name":"UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"IBD Unit, Centro per le Malattie dell\u2019Apparato Digerente (CEMAD), Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2346-1064","authenticated-orcid":false,"given":"Miriam","family":"Di Mattia","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), \u201cG. D\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Medicine and Ageing Sciences, \u201cG. D\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1513-1474","authenticated-orcid":false,"given":"Sara","family":"Troisi","sequence":"additional","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7266-6387","authenticated-orcid":false,"given":"Marianna","family":"Kashyrina","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DiMeS), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pizzoferrato","sequence":"additional","affiliation":[{"name":"UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Masi","sequence":"additional","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8481-4164","authenticated-orcid":false,"given":"Laura","family":"Parisio","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Ospedale Isola Tiberina Gemelli Isola, 00186 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9611-2490","authenticated-orcid":false,"given":"Maria Cristina","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Institute of Chemical Sciences and Technologies \u2018\u2018Giulio Natta\u2019\u2019 (SCITEC)-CNR, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Scagnoli","sequence":"additional","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Institute of Chemical Sciences and Technologies \u2018\u2018Giulio Natta\u2019\u2019 (SCITEC)-CNR, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Chieppa","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DiMeS), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Petito","sequence":"additional","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loris Riccardo","family":"Lopetuso","sequence":"additional","affiliation":[{"name":"IBD Unit, Centro per le Malattie dell\u2019Apparato Digerente (CEMAD), Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Life Science, Health, and Health Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-7541","authenticated-orcid":false,"given":"Franco","family":"Scaldaferri","sequence":"additional","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"IBD Unit, Centro per le Malattie dell\u2019Apparato Digerente (CEMAD), Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-7298","authenticated-orcid":false,"given":"Alfredo","family":"Papa","sequence":"additional","affiliation":[{"name":"Department of 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