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Lupinus albus is a legume rich in galactooligosaccharides (GOS) that functions as a prebiotic capable of modulating the gut microbiota and mitigating ulcerative colitis-related damage. This study aimed to elucidate the effect of GOS on gut microbiota modulation and the molecular mechanisms involved in epithelial restoration and inflammation reduction. Fifteen C57BL\/6 mice were randomly assigned to three groups (n = 5 per group): control (CTL), ulcerative colitis (UC), and ulcerative colitis + GOS (UC + GOS). UC was induced by administering 2% dextran sulfate sodium (DSS) in drinking water for seven days. The UC + GOS group received 2.5 g\/kg BW of GOS via gavage for 14 days. GOS administration improved mucus layer thickness, regulated the expression of tight junction proteins, reduced pro-inflammatory cytokine levels, and modulated the gut microbiota, preventing the loss of richness and diversity. Additionally, the expression of monocarboxylate transporters (MCTs) MCT1 and MCT4 was evaluated, and significant differences were observed between the groups across colon and cecum tissues. These findings suggest that GOS supplementation may play a potential role in attenuating ulcerative colitis by regulating the gut microbiota and the metabolic state of intestinal cells.<\/jats:p>","DOI":"10.3390\/ijms26167968","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T16:22:33Z","timestamp":1755534153000},"page":"7968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Galactooligosaccharides Promote Gut Barrier Integrity and Exert Anti-Inflammatory Effects in DSS-Induced Colitis Through Microbiota Modulation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1631-2370","authenticated-orcid":false,"given":"Lucila A.","family":"God\u00ednez-M\u00e9ndez","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n en Inmunolog\u00eda y Dermatolog\u00eda (CIINDE), Departamento de Fisiolog\u00eda, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"},{"name":"Departamento Acad\u00e9mico de Ciencias B\u00e1sicas, Universidad Aut\u00f3noma de Guadalajara, Av. 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