Impact of Zinc‐Dependent Enzymes on Zinc Deficiency and Inflammatory Response in Ulcerative Colitis

BACKGROUND AND AIM: Zinc (Zn) deficiency occurs in 40% of patients with ulcerative colitis (UC). Although Zn-dependent enzymes are involved in intestinal immune regulation, their relationships with Zn deficiency and mucosal inflammation remain unclear. This study aimed to investigate the associations among Zn-dependent enzyme activities, serum Zn levels, and mucosal inflammatory cytokine mRNA expression in UC. METHODS: Patients with UC who underwent colonoscopies from September 2019 to October 2020 were registered in a single-center prospective observational study. Serum Zn levels, serum and mucosal heat-resistant alkaline phosphatase (hrALP) activity, serum and mucosal ecto-5'-nucleotidase (NT5E)/CD73 activity, and mucosal inflammatory cytokine mRNA expression were evaluated. RESULTS: Twenty-nine patients with UC were enrolled. Serum Zn levels were lower in the nonclinical remission group and the non-endoscopic remission group. Tissue hrALP activity was higher and tissue NT5E/CD73 activity tended to be higher in Zn-deficient patients. Tissue hrALP was positively correlated with the Matts histological score, whereas tissue NT5E/CD73 activity showed a positive trend. Serum Zn levels were inversely correlated with tissue hrALP activity. Tissue hrALP and NT5E/CD73 activities were positively correlated with several mucosal inflammatory cytokines, whereas serum enzyme activities showed no significant correlations with inflammatory cytokine expression. CONCLUSIONS: Increased mucosal Zn-dependent enzyme activities were associated with histological inflammation, Zn deficiency, and mucosal inflammatory cytokine expression in UC. These findings suggest that mucosal Zn-dependent enzyme activity may reflect local inflammatory status and altered Zn homeostasis in UC.