{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T06:59:31Z","timestamp":1780901971713,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Butyrate, a microbiota-derived short-chain fatty acid, plays a central role in intestinal homeostasis, yet its concentration-dependent effects on human inflamed mucosa remain poorly defined. This study investigates the dose-dependent impact of butyrate on inflammatory signaling and epithelial architecture in ex vivo intestinal biopsies from patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn\u2019s disease (CD). Methods: Intestinal biopsies from six IBD patients (four UC, two CD) were cultured ex vivo for 24 h with calcium butyrate (5, 10, 100 mM). Cytokine secretion was analyzed by multiplex immunoassay, total protein release was quantified, and glandular morphology was assessed by stereological analysis. Results: Butyrate was associated with a dose-dependent reduction in pro-inflammatory cytokines-including TNF-\u03b1, IFN-\u03b3, IL-6, and IL-17-in both inflamed and non-inflamed tissue. Non-linear responses were observed for specific mediators, such as IP-10, which displayed a biphasic pattern in inflamed UC biopsies. Notably, UC and CD biopsies exhibited distinct response profiles: UC samples showed marked cytokine modulation, including reduction in IL-15, whereas CD samples, evaluated at 5 and 10 mM, showed limited modulation across conditions. A trend toward reduced total protein secretion was observed in diseased UC biopsies following butyrate exposure. Stereological analysis revealed preservation of glandular area at 5 mM, reduction at 10 mM, and extensive tissue disruption at 100 mM precluding structural evaluation. Conclusions: In this pilot study, butyrate exerts dose-dependent and disease-specific effects in human IBD mucosa within a narrow therapeutic window. These exploratory findings suggest that dose-optimized strategies for butyrate-based interventions may be particularly relevant in UC, although larger confirmatory studies are needed.<\/jats:p>","DOI":"10.3390\/metabo16060395","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:43:46Z","timestamp":1780897426000},"page":"395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Actions of Butyrate on Immunoepithelial Remodeling in Ex Vivo Intestinal Biopsies from Patients with Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1513-1474","authenticated-orcid":false,"given":"Sara","family":"Troisi","sequence":"first","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d 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\/0009-0009-8184-8559","authenticated-orcid":false,"given":"Cesare","family":"Pane","sequence":"additional","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8251-7358","authenticated-orcid":false,"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 \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1327-7642","authenticated-orcid":false,"given":"Filippo","family":"Biamonte","sequence":"additional","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Scannone","sequence":"additional","affiliation":[{"name":"Histopathology Unit, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1698-3660","authenticated-orcid":false,"given":"Antonio","family":"Cappa Spina","sequence":"additional","affiliation":[{"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\/0000-0003-2346-1064","authenticated-orcid":false,"given":"Miriam","family":"Di Mattia","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), Department of Medicine and Aging Science, G. D\u2019Annunzio University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0593-9327","authenticated-orcid":false,"given":"Valeria","family":"Emoli","sequence":"additional","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3927-591X","authenticated-orcid":false,"given":"Ivan","family":"Capobianco","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"IBD Unit, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6164-7826","authenticated-orcid":false,"given":"Sonia","family":"Distante","sequence":"additional","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0201-501X","authenticated-orcid":false,"given":"Barbara","family":"Rondinone","sequence":"additional","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4396-1613","authenticated-orcid":false,"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 \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6230-1779","authenticated-orcid":false,"given":"Antonio","family":"Gasbarrini","sequence":"additional","affiliation":[{"name":"CeMAD Translational Research Laboratories, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"IBD Unit, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loris Riccardo","family":"Lopetuso","sequence":"additional","affiliation":[{"name":"IBD Unit, Digestive Disease Center (CeMAD), Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario \u201cA. 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