Association Between Zinc Status and Tight Junction Integrity and Proinflammatory Cytokine Expression in Crohn's Disease

Aims

Zinc deficiency is common in patients with Crohn's disease (CD) and has been associated with adverse clinical outcomes. However, the relationship between zinc status and intestinal barrier integrity remains unclear. We investigated the association between serum zinc levels and the expression of tight junction (TJ) proteins and proinflammatory cytokines using paired intestinal biopsies from patients with CD. Methods and results: This retrospective observational study included patients with CD who underwent colonoscopic biopsies under both low zinc (< 80 μg/dL) and normal zinc (≥ 80 μg/dL) conditions between March 2017 and December 2023. Immunohistochemical staining was performed to assess TJ proteins (E-cadherin, zonula occludens-1 [ZO-1], occludin, and claudin-1) and proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-17, IL-12, and IL-23). Twelve patients were included in the main analysis, while eight who did not receive treatment intensification were included in the sub-analysis. In the main analysis, E-cadherin, ZO-1, and claudin-1 expression levels were significantly lower during the low zinc state, whereas IL-17 expression was significantly higher. Similar trends were observed in the sub-analysis. Additionally, the CD Activity Index was significantly higher, and hemoglobin and albumin levels were significantly lower during the low zinc state.