Hu Xiuchuan, Wang Rui, Kille Peter, Maret Wolfgang, Hogstrand Christer
Department of Nutritional Sciences, School of Life Course and Population Sciences, King's College London, London, UK.
School of Biosciences, Cardiff University, Cardiff, UK.
J Nutr Biochem. 2025 Jul;141:109909. doi: 10.1016/j.jnutbio.2025.109909. Epub 2025 Mar 26.
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 ZnSO 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 ZnSO 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 ZnSO 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).
锌以及芳烃受体（AHR）的几种生理相关配体都是促进肠道屏障功能的营养素。我们已经确定，AHR激活会上调肠道上皮细胞中锌转运体的表达，以增加细胞内锌浓度，从而改善上皮屏障功能。在此，我们研究了锌的氨基酸螯合物与AHR激活协同作用时，是否能够改善分化的Caco-2细胞上皮的屏障功能。Caco-2细胞上皮的功能测定表明，硫酸锌以及锌与赖氨酸和谷氨酸的螯合物，与生理性AHR激动剂6-甲酰基吲哚并[3,2-b]咔唑（FICZ）联合使用时，会在mRNA和蛋白质水平上增加紧密连接蛋白的表达。在培养基中存在硫酸锌或氨基酸锌螯合物的情况下，FICZ会使锌同等程度地增加进入上皮细胞的摄取量。我们得出结论，在存在FICZ的情况下，锌与赖氨酸和谷氨酸的螯合物在降低Caco-2细胞上皮通透性方面与硫酸锌一样有效。结果表明，膳食补充生物可利用形式的锌以及营养性AHR激动剂可能有助于改善肠道屏障功能，并有助于预防炎症性肠病（IBD）。
