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Background Inflammatory Bowel Disease (IBD) is characterized by impaired gut barrier function and dysregulated intestinal immunity. Vitamin D, acting through vitamin D receptors (VDR), helps maintain epithelial integrity and modulate immune responses. Experimental studies show that VDR deficiency increases susceptibility to severe colitis, underscoring its role in intestinal homeostasis. However, the role of VDR expression in patients with ulcerative colitis (UC) and its association with disease activity and extent remains unclear.Methods Prospective cases were defined as patients with UC and their clinical, endoscopic and histological activity was assessed using standard criteria. Patients undergoing colonoscopy for non-IBD indications served as controls. Colonoscopy was performed to assess disease activity, extent and biopsies were obtained from all six colonic segments. Biopsies were stained for VDR by Immunohistochemistry (IHC) [anti-VDR antibody [VDR (D-6): sc-13133, dilution 1:400]]. VDR staining was graded (0–3; IDDF2026-ABS-0532 Figure 1), and a cumulative VDR score was calculated by summing segmental scores. Statistical analysis was performed using SPSS (v 26) and a p-value of <0.05 was taken as significant.Results A total of 96 patients with UC and 55 controls were enrolled. The median VDR score of the surface epithelium was lower in cases compared to controls across all the segments (8[8] vs 14[8]; p<0.001; IDDF2026-ABS-0532 Figure 2). VDR expression was higher in the surface epithelium compared to the crypt base. The proportion of patients showing a higher VDR score decreases with increasing disease extent. (Controls (76%) vs E1 (47%) vs E2(31%) vs E3(38%); p<0.001). The median VDR score was lowest amongst those with active disease compared to those in remission and controls. (6[9] vs 9[7] vs 14[8]; p<0.001; IDDF2026-ABS-0532 Figure 3) VDR expression was inversely correlated with histological activity, indicating that greater histological inflammation was associated with lower VDR levels. (n=891; rho=0.412; p<0.001)Conclusions Patients with UC were found to have lower VDR expression across all colonic segments compared to controls, with lower levels associated with greater disease extent and higher endoscopic activity. Low VDR expression at the particular mucosal site was associated with more severe mucosal inflammation. These findings suggest the role of vitamin D signaling in mucosal immunity and indicate that modulation of VDR pathways may influence disease progression.Abstract IDDF2026-ABS-0532 Figure 1Abstract IDDF2026-ABS-0532 Figure 2Abstract IDDF2026-ABS-0532 Figure 3