Effect of Long-Term and Short-Term Imbalanced Zn Manipulation on Gut Microbiota and Screening for Microbial Markers Sensitive to Zinc Status

Zinc (Zn) imbalance is a common single-nutrient disorder worldwide, but little is known about the short-term and long-term effects of imbalanced dietary zinc in the intestinal microbiome. Here, 3-week-old C57BL/6 mice were fed diets supplemented with Zn at the doses of 0 (low Zn), 30 (control Zn), 150 (high Zn), and 600 mg/kg of body weight (excess Zn) for 4 weeks (short term) and 8 weeks (long term). The gut bacterial composition at the phyla, genus, and species levels were changed as the result of the imbalanced Zn diet (e.g., Lactobacillus reuteri and Akkermansia muciniphila). Moreover, pathways including carbohydrate, glycan, and nucleotide metabolism were decreased by a short-term low-Zn diet. Valeriate production was suppressed by a long-term low-Zn diet. Pathways such as drug resistance and infectious diseases were upregulated in high- and excess-Zn diets over 4-week and 8-week intervals. Long-term zinc fortification doses, especially at the high-Zn level, suppressed the abundance of short-chain fatty acids (SCFAs)-producing genera as well as the concentrations of metabolites. Finally, Melainabacteria (phylum) and Desulfovibrio sp. strain ABHU2SB (species) were identified to be potential markers for Zn status with high accuracy (area under the curve [AUC], >0.8). Collectively, this study identified significant changes in gut microbial composition and its metabolite concentration in altered Zn-fed mice and the relevant microbial markers for Zn status. IMPORTANCE Zn insufficiency is an essential health problem in developing countries. To prevent the occurrence of zinc deficit, zinc fortification and supplementation are widely used. However, in developed countries, the amounts of Zn consumed often exceed the tolerable upper intake limit. Our results demonstrated that dietary Zn is an essential mediator of microbial community structure and that both Zn deficiency and Zn overdose can generate a dysbiosis in the gut microbiota. Moreover, specific microbial biomarkers of Zn status were identified and correlated with serum Zn level. Our study found that a short-term low-Zn diet (0 mg/kg) and a long-term high-zinc diet (150 mg/kg) had obvious negative effects in a mouse model. Thus, these results indicate that the provision and duration of supplemental Zn should be approached with caution.