Zinc supplementation modulates T helper 17 cells via the gut microbiome

Abstract

Abstract Zinc is a dietary micronutrient that regulates various biological processes. Zinc is important for replication and survival of microbes and, as a result, a common strategy of the immune system is to steal zinc away from disease-causing microbes to prevent their growth. Recent studies show that changes in levels of dietary zinc can alter the composition of the gut microbiota, however how this impacts mucosal immune responses in the gut is not known. Here, we show that supplementing mice with zinc sulphate, a commonly used therapy for treating diarrheal episodes, in drinking water for a week resulted in significant changes in gut microbial composition as well drastic reduction in microbial diversity. More importantly. we saw that zinc supplementation attenuated the T helper17 cell number and activity in murine small intestine. To determine if zinc-dependent changes in gut microbiota are sufficient to limit Th17 response, we transplanted the microbiome from zinc treated mice into germ-free mice. We saw that germ-free mice that received cecal contents from zinc treated mice have reduced Th17 response, thus establishing that dietary zinc changes immune potential of the gut microbiome. Th17 cells mediate antimicrobial response in the gut and are involved in the pathogenesis of many autoimmune diseases. Our work thus provides a novel nutritional approach for remodeling microbiota to dampen inflammatory immune responses in the gut.