Inflammatory bowel disease (IBD), particularly Crohn's disease, is characterized by impaired epithelial barrier function. This study investigates the changes in tight junction proteins, specifically claudins 2, 5, and 8, in active Crohn's disease. The results show that claudin 2 is upregulated, while claudins 5 and 8 are downregulated and redistributed. These changes lead to discontinuous tight junctions and barrier dysfunction. Additionally, increased epithelial apoptosis contributes to barrier dysfunction in active Crohn's disease. In contrast, barrier function, tight junction proteins, and apoptosis are unaffected in remission. Claudin 2 upregulation is less pronounced in active Crohn's disease compared to active ulcerative colitis and is inducible by TNFα. The study also highlights the role of epithelial apoptosis in barrier dysfunction, showing increased apoptosis in active Crohn's disease compared to controls. The findings suggest that altered tight junction architecture and increased apoptosis are key factors in barrier dysfunction in active Crohn's disease. The study used various techniques, including impedance analysis, conductance scanning, freeze fracture electron microscopy, and immunohistochemistry, to assess barrier function and tight junction protein expression. The results indicate that changes in claudin expression and epithelial apoptosis contribute to the structural and functional alterations in the intestinal barrier in active Crohn's disease.Inflammatory bowel disease (IBD), particularly Crohn's disease, is characterized by impaired epithelial barrier function. This study investigates the changes in tight junction proteins, specifically claudins 2, 5, and 8, in active Crohn's disease. The results show that claudin 2 is upregulated, while claudins 5 and 8 are downregulated and redistributed. These changes lead to discontinuous tight junctions and barrier dysfunction. Additionally, increased epithelial apoptosis contributes to barrier dysfunction in active Crohn's disease. In contrast, barrier function, tight junction proteins, and apoptosis are unaffected in remission. Claudin 2 upregulation is less pronounced in active Crohn's disease compared to active ulcerative colitis and is inducible by TNFα. The study also highlights the role of epithelial apoptosis in barrier dysfunction, showing increased apoptosis in active Crohn's disease compared to controls. The findings suggest that altered tight junction architecture and increased apoptosis are key factors in barrier dysfunction in active Crohn's disease. The study used various techniques, including impedance analysis, conductance scanning, freeze fracture electron microscopy, and immunohistochemistry, to assess barrier function and tight junction protein expression. The results indicate that changes in claudin expression and epithelial apoptosis contribute to the structural and functional alterations in the intestinal barrier in active Crohn's disease.