Zinc amino acid chelate and the Aryl Hydrocarbon Receptor (AHR) cooperate in improving the barrier function of a Caco-2 cell intestinal epithelium.

Abstract

Zinc and several physiologically relevant ligands of the Aryl Hydrocarbon Receptor (AHR) are nutrients that promote intestinal barrier function. We have identified that AHR activation upregulates the expression of zinc importers in the intestinal epithelium to increase intracellular zinc concentrations, which leads to improved epithelial barrier function. Here, we investigated if an amino acid chelate of zinc, in cooperation with AHR activation, can improve the barrier function of a differentiated Caco-2 cell epithelium. Functional assays of the Caco-2 cell epithelium demonstrate that both ZnSO₄ and a lysine and glutamic acid chelate of Zn, in combination with the physiological AHR agonist 6-formylindolo[3,2-b]carbazole (FICZ), increase expression of tight junction proteins at the mRNA and protein levels. FICZ increases uptake of zinc into the epithelium in the presence of ZnSO₄ or the amino acid Zn chelate in the medium to equal extents. We conclude that the lysine and glutamic acid chelate of Zn is as efficacious as ZnSO₄ in reducing permeability of the Caco-2 cell epithelium in the presence of FICZ. The results suggest that dietary supplementation with bioavailable forms of zinc together with nutritional AHR agonists may be beneficial in improving gut barrier function and help prevent inflammatory bowel disease (IBD).