A Guide to Human Zinc Absorption: General Overview and Recent Advances of In Vitro Intestinal Models

Abstract

Zinc absorption in the small intestine is one of the main mechanisms regulating the systemic homeostasis of this essential trace element. This review summarizes the key aspects of human zinc homeostasis and distribution. In particular, current knowledge on human intestinal zinc absorption and the influence of diet-derived factors on bioaccessibility and bioavailability as well as intrinsic luminal and basolateral factors with an impact on zinc uptake are discussed. Their investigation is increasingly performed using in vitro cellular intestinal models, which are continually being refined and keep gaining importance for studying zinc uptake and transport via the human intestinal epithelium. The vast majority of these models is based on the human intestinal cell line Caco-2 in combination with other relevant components of the intestinal epithelium, such as mucin-secreting goblet cells and in vitro digestion models, and applying improved compositions of apical and basolateral media to mimic the in vivo situation as closely as possible. Particular emphasis is placed on summarizing previous applications as well as key results of these models, comparing their results to data obtained in humans, and discussing their advantages and limitations.

Zinc Deficiency Disturbs Mucin Expression, O-Glycosylation and Secretion by Intestinal Goblet Cells

“…The zinc requirements of ZD cells are probably elevated. Hence, they might absorb more zinc ( Figure 3 B) in order to maintain cellular zinc homeostasis, similar to what is known for enterocytes (reviewed in [ 2 ]). The differential regulation of intestinal zinc transporters in response to nutritional zinc controls zinc absorption and distribution in vivo [ 2 ].…”

“…Hence, they might absorb more zinc ( Figure 3 B) in order to maintain cellular zinc homeostasis, similar to what is known for enterocytes (reviewed in [ 2 ]). The differential regulation of intestinal zinc transporters in response to nutritional zinc controls zinc absorption and distribution in vivo [ 2 ]. Intestinal ZIP-4 and ZIP-5 are known to be predominantly regulated in a translational and post-translational manner during zinc deficiency [ 2 ], yet upregulation of ZIP-4 mRNA in zinc deficiency was already reported in in vivo small intestine of ZD rats or mice [ 28 , 29 ].…”

“…In the intestinal tract, zinc is absorbed into intestinal epithelial cells via ZIP-4 at their apical membrane and exported into the blood by basolaterally localized ZnT1. ZIP-5 at the basolateral membrane transports systemic zinc from the blood back into the intestinal epithelial cells, whereas the bidirectional transporter ZnT5 variant B (ZnT5B) at the apical membrane is discussed to export cellular zinc into the intestinal lumen as well as import the metal into cells [ 2 ]. To date, there are no studies on their expression pattern in HT-29-MTX.…”

“…The differential regulation of intestinal zinc transporters in response to nutritional zinc controls zinc absorption and distribution in vivo [ 2 ]. Intestinal ZIP-4 and ZIP-5 are known to be predominantly regulated in a translational and post-translational manner during zinc deficiency [ 2 ], yet upregulation of ZIP-4 mRNA in zinc deficiency was already reported in in vivo small intestine of ZD rats or mice [ 28 , 29 ]. Likewise, it is known that cellular zinc levels regulate ZnT1 expression via metal regulatory transcription factor 1 (MTF1) [ 30 ].…”

“…The essential micronutrient zinc is required for catalytic, structural, and regulatory functions of various zinc-metalloproteins in the human body [ 1 ]. Accordingly, deprivation of this metal is associated with severe health consequences [ 2 ]. Prolonged deficiency enhances the risk of infection, often connected with diarrhea and impaired wound healing, resulting in high morbidity [ 3 ].…”