Integrated multi-omics uncovers reliable potential biomarkers and adverse effects of zinc deficiency

Background: Zinc deficiency is a worldwide public health problem. Currently, there are no established biomarkers available for the accurate diagnosis of zinc-deficiency in individuals. Additionally, a comprehensive view of the adverse effects of zinc deficiency is lacking. Our aim was to identify superior biomarkers of zinc deficiency and uncover the adverse effects of zinc deficiency. Methods: We performed multi-omics analysis using serum proteomics-metabolomics and liver proteomics on zinc-deficient rats to identify candidate biomarkers and reveal the associated adverse effects of zinc deficiency. Secondly, the candidate biomarkers were validated in two zinc-deficient populations and an RCT zinc supplementation trial on a zinc-deficient population. Results: Our integrated multi-omics approach revealed numerous biomarkers (>2000) and glutathione metabolism as the most important changed pathway in zinc deficiency. Three candidate biomarkers from glutathione metabolism were validated in repeated zinc-deficient rats by quantitative analysis. Only glutathione sulfotransferase omega-1 (GSTO1) (among 3 candidate biomarkers) was validated in the two zinc-deficient populations and zinc-supplemented population. Compared with serum zinc, serum GSTO1 yielded a better response to zinc supplementation and a higher correlation coefficient with zinc intake and the AUC value and has the potential for diagnosing zinc deficiency. By integrated multi-omics, we identified both established and novel adverse effects of zinc deficiency. Conclusions: Our integrated multi-omics analysis revealed more complete information about zinc deficiency; GSTO1 was found to be a reliable potential biomarker for diagnosis of zinc deficiency. This trial is registered at http://www.chictr.org.cn/registry.aspx as ChiCTR1900028162. (c) 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.