Chronic Dietary Zinc Deficiency Alters Gut Microbiota Composition and Function

: Zinc (Zn) deficiency is a prevalent micronutrient insufficiency. Although the gut is a vital organ for Zn utilization, and Zn deficiency is associated with impaired intestinal permeability and a global decrease in gastrointestinal health, alterations in the gut microbial ecology of the host under conditions of Zn deficiency have yet to be studied. By conducting a series of long-term in vivo ( Gallus gallus ) feeding trials, we aimed to characterize distinct cecal microbiota shifts induced by chronic dietary Zn depletion in the context of complete diets based on Zn-biofortified food crops that are relevant to target populations, and in geographical regions where dietary Zn deficiency is a major health concern. We demonstrate that Zn deficiency induces significant taxonomic alterations and decreases overall species richness and diversity, establishing a microbial profile resembling that of various other pathological states. Through metagenomic analysis, we show that the predicted Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways responsible for macro-and micronutrient uptake are significantly depleted under Zn deficiency; along with concomitant decreases in beneficial short-chain fatty acids, such depletions may further preclude optimal host Zn availability. We also identify several candidate microbes that may play a significant role in modulating the bioavailability and utilization of dietary Zn during prolonged deficiency. Our results are the first to characterize a unique and dysbiotic cecal microbiota during Zn deficiency, and they provide evidence for such microbial perturbations as potential effectors of the Zn-deficient phenotype.