Association Between Zinc Status and Tight Junction Integrity and Proinflammatory Cytokine Expression in Crohn's Disease.
- 1Department of Gastroenterology and Hepatology Hokkaido University Graduate School of Medicine Sapporo Hokkaido Japan.
Abstract
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.Conclusion
Low zinc status was associated with altered expression of TJ proteins and IL-17 in the intestinal mucosa of patients with CD. These findings suggest that zinc status may be linked to epithelial barrier integrity and mucosal immune responses in CD. Although further validation is required, zinc supplementation may represent a simple and accessible adjunct to current therapies.
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BibTeX
@article{nomura2026association,
title = {{Association Between Zinc Status and Tight Junction Integrity and Proinflammatory Cytokine Expression in Crohn's Disease.}},
author = {Asako Nomura and Shinsuke Otagiri and Takehiko Katsurada and Sho Tanaka and Kenta Fujihata and Naoya Sakamoto},
journal = {JGH open : an open access journal of gastroenterology and hepatology},
year = {2026},
month = oct,
doi = {10.1002/jgh3.70485},
url = {https://europepmc.org/article/MED/42926740},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Association Between Zinc Status and Tight Junction Integrity and Proinflammatory Cytokine Expression in Crohn's Disease.
AU - Asako Nomura
AU - Shinsuke Otagiri
AU - Takehiko Katsurada
AU - Sho Tanaka
AU - Kenta Fujihata
AU - Naoya Sakamoto
PY - 2026
DA - 2026/10/23
JO - JGH open : an open access journal of gastroenterology and hepatology
DO - 10.1002/jgh3.70485
UR - https://europepmc.org/article/MED/42926740
AB - 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.Conclusion Low zinc status was associated with altered expression of TJ proteins and IL-17 in the intestinal mucosa of patients with CD. These findings suggest that zinc status may be linked to epithelial barrier integrity and mucosal immune responses in CD. Although further validation is required, zinc supplementation may represent a simple and accessible adjunct to current therapies.
SN - 2397-9070
ER -