{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:08:00Z","timestamp":1780337280090,"version":"3.54.1"},"reference-count":39,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation","award":["TCRD-TPE-109-50"],"award-info":[{"award-number":["TCRD-TPE-109-50"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gut barrier dysfunction and increased intestinal permeability are closely linked to the pathogenesis of type 1 diabetes and its complications. Streptozotocin (STZ)-induced diabetic mice, which mimic \u03b2-cell destruction and insulin deficiency, provide a widely used model for studying type 1 diabetes-associated intestinal barrier impairment. However, the cellular pathways mediating this dysfunction, particularly the role of goblet cells, remain incompletely elucidated. This study aimed to investigate the association between the gut barrier function and diabetes. Using real-time intravital multiphoton microscopy, we investigated intestinal barrier integrity in STZ-induced type 1 diabetic mice. Three groups were analysed: the control, STZ-diabetic, and STZ-diabetic mice treated with fructooligosaccharide (FOS) for 1 week. Intestinal permeability was assessed by measuring fluorescein isothiocyanate (FITC)-dextran concentrations in the portal vein and visualising translocation into villi. Epithelial morphology was examined, focusing on goblet cell density and leakage pathways. STZ-diabetic mice demonstrated a significant increase in intestinal permeability, evidenced by elevated FITC-dextran levels in the portal vein and villi. Multiphoton imaging revealed a notable rise in the goblet cell-to-enterocyte ratio in diabetic mice, while the gap density remained unchanged. The predominant route of macromolecular leakage in STZ-diabetic mice was via goblet cells rather than by paracellular gaps. One-week FOS supplementation significantly reduced goblet cell density and partially restored barrier function without altering the distribution of leakage pathways. These findings highlight goblet cell-mediated transcellular leakage as a major mechanism of gut barrier dysfunction in type 1 diabetic mice. Short-term FOS treatment partially reverses these alterations. Targeting goblet cell function may offer a promising therapeutic strategy to restore gut barrier integrity in diabetes.<\/jats:p>","DOI":"10.3390\/ijms26188890","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T12:34:03Z","timestamp":1757680443000},"page":"8890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Goblet Cell-Mediated Pathway: A Major Contributor to Increased Intestinal Permeability in Streptozotocin-Induced Type 1 Diabetic Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Ming-Hsun","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Surgery, National Taiwan University Hospital, Taipei 100229, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee-Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiann-Hwa","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231405, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 970374, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieh-Wen","family":"Lai","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzu Chi University, Hualien 970374, Taiwan"},{"name":"Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231405, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2567.2011.03506.x","article-title":"Epithelial barrier biology: Good fences make good neighbours","volume":"135","author":"Moens","year":"2012","journal-title":"Immunology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/BF01706424","article-title":"Intestinal permeability in the critically ill","volume":"18","author":"Harris","year":"1992","journal-title":"Intensive Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1111\/j.1365-2036.2006.03174.x","article-title":"Review article: Bacterial translocation in the critically ill\u2014Evidence and methods of prevention","volume":"25","author":"Gatt","year":"2007","journal-title":"Aliment. 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