{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:20:03Z","timestamp":1787239203169,"version":"build-2736575974"},"reference-count":46,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100017726","name":"Fondazione Diabete Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017726","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001648","name":"European Foundation for the Study of Diabetes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001648","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015410","name":"Societ\u00e0 Italiana di Medicina Interna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2022LWXFM4"],"award-info":[{"award-number":["2022LWXFM4"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>The farnesoid X receptor (FXR)\u2013fibroblast growth factor 19 (FGF19) axis is involved in maintaining glucose homeostasis and gut tight-junction (TJ) integrity. We evaluated whether individuals with prediabetes or type 2 diabetes (T2D) have altered intestinal FXR-FGF19 signaling and barrier function and whether high-glucose (HG) exposure may cause these aberrations. Moreover, we tested beneficial effects of the FXR agonist obeticholic acid (OCA) on intestinal FXR signaling in individuals with prediabetes or T2D. Included were 60 individuals with different glucose tolerance (normal glucose tolerance [NGT; n = 25], prediabetes [n = 19], or T2D [n = 16]) who underwent ileocolonoscopy with collection of ileal mucosa biopsy specimens, which were used for expression profiling analysis of the FXR\/FGF19\/TJ axis and tissue culture experiments. Individuals with prediabetes or T2D displayed lower ileal levels of FXR and its target genes FGF19 and TJ proteins zonula, occludens-1, occludin, and claudin-1, along with increased proinflammatory nuclear factor-\u03baB (NF-\u03baB) activity and cytokines expression compared with those with NGT. HG exposure on ileal explants collected from NGT individuals hampered the FXR\/FGF19\/TJ axis. OCA treatment on ileal fragments of individuals with prediabetes\/T2D was able to restore FGF19 synthesis and secretion, TJ expression, and counteract NF-\u03baB activity and cytokines expression. In conclusion, OCA treatment counteracts T2D-related intestinal abnormalities in the FXR\/FGF19\/TJ axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>The intestinal farnesoid X receptor (FXR)\/fibroblast growth factor 19 (FGF19) axis is involved in maintaining glucose homeostasis and gut barrier function in animals. Do individuals with prediabetes and type 2 diabetes exhibit a compromised intestinal FXR\/FGF19\/barrier integrity axis? Can obeticholic acid (OCA) treatment counteract diabetes-related gut mucosa dysfunction? A downregulation of ileal FXR\/FGF19\/tight-junctions signaling occurs in individuals with hyperglycemia. OCA-mediated FXR activation reverts diabetes-related alterations. OCA-mediated intestinal FXR activation in individuals with hyperglycemia may represent a strategy for restoring FGF19 synthesis with positive effects on gut barrier.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0035","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T12:34:02Z","timestamp":1750163642000},"page":"1399-1410","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":5,"title":["FXR Stimulation by Obeticholic Acid Treatment Restores Gut Mucosa Functional and Structural Integrity in Individuals With Altered Glucose Tolerance"],"prefix":"10.2337","volume":"74","author":[{"given":"Francesca","family":"De Vito","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro 1 , Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Marasco","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University Magna Graecia of Catanzaro 2 , Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelina","family":"Suraci","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University Magna Graecia of Catanzaro 2 , Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Facciolo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro 1 , Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta Letizia","family":"Hribal","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro 1 , Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Sesti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, University of Rome-Sapienza 3 , Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9375-1513","authenticated-orcid":false,"given":"Francesco","family":"Andreozzi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro 1 , Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Luzza","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University Magna Graecia of Catanzaro 2 , Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9485-8793","authenticated-orcid":false,"given":"Teresa Vanessa","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro 1 , Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"2026061114072725100_B1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","article-title":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021","volume":"402","author":"GBD 2021 Diabetes Collaborators","year":"2023","journal-title":"Lancet"},{"key":"2026061114072725100_B2","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.2337\/dc22-2376","article-title":"Global prevalence of prediabetes","volume":"46","author":"Rooney","year":"2023","journal-title":"Diabetes 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