Vitamin D in mucosal healing: therapeutic potential and current evidence in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic and progressive disorder of the digestive tract, including Crohn's disease and ulcerative colitis. Over the last decade, IBD has been extensively studied due to its association with dysregulated intestinal microbiota, increased mucosal permeability, and immune imbalance. Despite available pharmacological treatments, there is no definitive cure. Mucosal healing (MH) has emerged as a crucial therapeutic target, as it aims to restore the integrity of inflamed mucosae and is associated with improved clinical outcomes. However, most clinical studies rely primarily on clinical indices rather than direct endoscopic or histologic assessment of MH, and the optimal vitamin D (VD) dosing required to achieve true MH remains unclear. This review aims to examine the diverse functions of VD in modulating pathways relevant to MH within the context of IBD, highlighting its role in immune modulation, intestinal barrier integrity, and gut microbiota composition, and to discuss its potential therapeutic value in IBD management. Relevant experimental, translational, and human clinical studies focusing on VD status, supplementation, and mechanisms related to MH, immune regulation, and intestinal barrier function in IBD were considered. MH involves epithelial restitution, cell proliferation, and differentiation, and its achievement has been associated with reduced symptoms, lower relapse rates, and decreased need for surgical interventions. Beyond its traditional role in bone health, VD plays a critical role in preserving intestinal barrier integrity and regulating immune homeostasis. While biological evidence indicates that VD modulates immune responses, enhances tight junction integrity, and influences gut microbiota composition, clinical data primarily support its role in improving clinical and biochemical disease activity rather than definitively inducing mucosal repair. This review highlights VD as a relevant immunomodulatory and barrier-protective factor with potential complementary value in the clinical management of patients with IBD.