{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:34:37Z","timestamp":1791588877922,"version":"4.3.4"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: The interaction between probiotics and the vitamin D\/vitamin D receptor (VDR) pathway has been increasingly explored as a potential mechanism for immune modulation in inflammatory bowel disease (IBD). Lactobacillus rhamnosus GG (LGG) has shown promising results in ulcerative colitis (UC) patients, but its effect on the VDR pathway remains unexplored in humans. Aim: To test the hypothesis that LGG can stimulate the vitamin D\/VDR pathway and modulate mucosal-adherent microbiota. Methods: In this study, we analyzed a subgroup of 13 patients from the LGGinUC trial, in which UC patients with mild-to-moderate disease activity received LGG monotherapy for four weeks. Colonic biopsy samples were collected before and after treatment to evaluate VDR expression via RT-qPCR and immunohistochemistry. Mucosal-adherent microbiota was also analyzed by DNA extraction and next-generation sequencing (NGS). Results: LGG administration significantly increased VDR mRNA expression in colonic mucosa (p &lt; 0.05), with a corresponding rise in VDR protein levels in both epithelial and sub-epithelial compartments. Microbiota analysis revealed a reduction in \u03b1-diversity, primarily due to a decrease in commensal bacterial species, while \u03b2-diversity remained largely unchanged. Conclusions: Although the present results have to be considered preliminary, this is the first human study demonstrating that probiotic supplementation can upregulate VDR expression in colonic mucosa. We propose that LGG may exert its beneficial effects in UC by stimulating the VDR pathway, which in turn modulates mucosal immunity and microbiota composition. Further studies with larger sample sizes and longer treatment durations are needed to validate these findings and explore their therapeutic implications.<\/jats:p>","DOI":"10.3390\/ph18111651","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"1651","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Lactobacillus rhamnosus GG Administration Is Associated with Stimulation of Vitamin D\/VDR Pathway and Mucosal Microbiota Modulation in Ulcerative Colitis Patients: A Pilot Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9985-7490","authenticated-orcid":false,"given":"Cristiano","family":"Pagnini","sequence":"first","affiliation":[{"name":"Gastroenterology and Digestive Endoscopy Department, S. Giovanni Addolorata Hospital, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6957-2718","authenticated-orcid":false,"given":"Manuele","family":"Gori","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology (IBBC)\u2014National Research Council (CNR), International Campus \u201cA. Buzzati-Traverso\u201d, Via E. Ramarini 32, Monterotondo Scalo, 00015 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carla","family":"Di Paolo","sequence":"additional","affiliation":[{"name":"Gastroenterology and Digestive Endoscopy Department, S. Giovanni Addolorata Hospital, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Urgesi","sequence":"additional","affiliation":[{"name":"Gastroenterology and Digestive Endoscopy Department, S. Giovanni Addolorata Hospital, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1351-3641","authenticated-orcid":false,"given":"Claudia","family":"Cicione","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Orthopaedic, Research Unit of Orthopaedic Surgery, Campus Bio-Medico University of Rome, Via A. del Portillo 21, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Zingariello","sequence":"additional","affiliation":[{"name":"Unit of Microscopic and Ultrastructural Anatomy, Department of Medicine, Campus Bio-Medico University of Rome, Via A. del Portillo 21, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Arciprete","sequence":"additional","affiliation":[{"name":"Unit of Microscopic and Ultrastructural Anatomy, Department of Medicine, Campus Bio-Medico University of Rome, Via A. del Portillo 21, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viola","family":"Velardi","sequence":"additional","affiliation":[{"name":"Unit of Microscopic and Ultrastructural Anatomy, Department of Medicine, Campus Bio-Medico University of Rome, Via A. del Portillo 21, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2431-8270","authenticated-orcid":false,"given":"Elisa","family":"Viciani","sequence":"additional","affiliation":[{"name":"Wellmicro Srl, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Padella","sequence":"additional","affiliation":[{"name":"Wellmicro Srl, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8131-974X","authenticated-orcid":false,"given":"Andrea","family":"Castagnetti","sequence":"additional","affiliation":[{"name":"Wellmicro Srl, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giovanna","family":"Graziani","sequence":"additional","affiliation":[{"name":"Gastroenterology and Digestive Endoscopy Department, S. Giovanni Addolorata Hospital, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Delle Fave","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"},{"name":"S. Andrea ETS, 00199 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s41579-025-01163-0","article-title":"Microbiota in inflammatory bowel disease: Mechanisms of disease and therapeutic opportunities","volume":"23","author":"Iliev","year":"2025","journal-title":"Nat. Rev. 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