Roles of zinc in the gut-liver axis

The gut and the liver are the main organs in the regulation and distribution of zinc. Therefore, gut and liver disease impact zinc functions in other organs. Many of the phenomenological observations made in the past century concerning the role of zinc in growth and development and the role of zinc deficiency in many diseases are now better understood on the basis of zinc's remarkable catalytic, structural, and regulatory functions in over 3200 human proteins and its functions as an ionic messenger similar to calcium in intra- and extracellular communication, regulation of metabolism, and gene expression. Zinc has key roles in carbohydrate and lipid metabolism, nitrogen balance, pH control, and the synthesis and degradation of proteins. Its classification as a trace element distracts from its global significance in the proliferation and differentiation of all cells. Zinc is at least as important as iron, if not even more so. Its intricate cellular regulation by 24 membrane zinc transporters, a dozen metallothioneins and other zinc homeostatic proteins supports this tenet. This review will summarize the role of zinc in the integrity of the intestinal barrier, in maintaining a healthy gut, and, through the gut-liver axis, a healthy liver. Zinc is critical for a proper immune response to support and control inflammation, in fighting off insults and repairing tissues, but also in avoiding chronic inflammation. About 75% of patients with decompensated liver cirrhosis are zinc deficient. Zinc deficiency, a prooxidant and proinflammatory condition, needs clinical attention in liver disease, should include attention to gut health, and involve pharmacological treatment with supplemental zinc. Monotherapy with zinc alone, however, is not the answer. Along with zinc, additional therapeutics are required to restore intestinal and hepatic functions.