Abstract

A Metabolic Signature for Cadmium Exposure in Two Human Populations: A Proof of Concept Study for Exposome Research

Alexandros Siskos, Research Associate, Imperial College London

The human exposome represents the total accumulation of human environmental exposures, from conception onwards, and the effect of these exposures to human health and disease. To elucidate the impact of heavy metal exposure on the metabolome, 950 human plasma samples from two different European populations (NSHDS/Sweden and EPIC/Italy) were characterised using untargeted UPLC-QTof-MS profiling as part of the FP7 EnviroGenoMarkers Project (EGM). EGM seeks to use the “meet in the middle” approach to identify -omics biomarkers associated with both environmental exposures and disease. Cadmium produces consistent effects on metabolite levels in plasma across two different European populations at low exposure levels. Cadmium reduces levels of heam metabolites biliverdin and bilirubin and also of the omega-3 docosahexaenoic acid (DHA). These metabolites are known endogenous antioxidants and their production is activated downstream of the Nrf2 pathway. This signature appears to be a Cd-specific metabolic effect, independent to lead or smoking. This study demonstrates the potential of metabolomics in exposome research and identifies previously unreported effects of cadmium exposure on systemic metabolism in humans.