Zinc Status Elicits Age-Dependent Effects in the Gut Microbiome

Abstract Objectives Zinc is an essential micronutrient critical for a variety of cellular processes, including immune function. In US, 12% of the population do not consume the EAR for zinc. In older populations the prevalence of inadequate zinc intake increases to ∼40%. Moreover, zinc levels are also often depressed in aged individuals, even when consuming a zinc-adequate diet. Thus, older populations can be highly susceptible to zinc deficiency. Both zinc deficiency and aging are associated with progressive immune dysfunction and chronic inflammation that could be correlated with the promotion of many age-related diseases. Increasing evidence indicates that the interaction among gut microbiota, the immune system, and diet contributes to age-related inflammation. Objectives: The goal of this study is to determine the importance of zinc status and age with respect to composition of the gut microbiome. We hypothesize that age and zinc status are correlated with specific taxa in the gut microbiome. Further, we expect to see additional correlations, both positive and negative, between these significant taxa and markers of host inflammation. Methods We studied the effects of dietary zinc supplementation and marginal zinc deficiency on changes in microbial communities in young and old mice. Young (2 mo) and old (24 mo) C57Bl/6 mice were fed a zinc adequate (30ppm Zn), zinc supplemented (300ppm Zn), or marginal zinc deficient (6 ppm Zn) diet for six weeks. 16S rRNA amplicon sequencing was performed on fecal samples at study start and end; cecal and colon samples at study end. Results Age correlated with overall microbial composition in the gut, according to a PERMANOVA test and a permutation test, regardless of zinc status. Gut microbiome content of young mice had significant overall correlation with zinc status, while the gut microbiome of old mice was not significantly affected by zinc status. Conclusions Age effects on the microbiome are significant and must be considered when studying effects of diet on the host gut microbiome. Zinc status, especially deficiency, elicits a varied effect on the microbiome that is dependent upon host age. Sampling site (i.e., colon, cecum, feces) had a small but significant effect on specific microbial taxa. Funding Sources NIFA, USDA.