Metabolic signatures of population exposure to metal mixtures: A metabolome-wide association study

Numerous studies have explored the health impacts of individual metal exposures, yet the effects of metal mixtures on human endogenous metabolism remain largely unexplored. We aimed to assess the serum metabolic signatures of people exposed to metal mixtures. Serum and urine samples were collected from 186 workers at a steel factory in Anhui, China, in September 2019. Inductively coupled plasma mass spectrometry was used to analyze the concentrations of 23 metal elements. The serum metabolome was determined by liquid chromatography-mass spectrometry (LC-MS). A metabolome-wide association study (MWAS) was performed across the metal exposures and metabolism using quantile g-computation modeling. Pathway enrichment analysis was performed using MetaboAnalyst. We identified 226 metabolites associated with metal mixtures, primarily involving lipid metabolism (glycerophospholipids, sphingolipids), amino acid metabolism (arginine and proline, alanine, aspartate and glutamate metabolism) and caffeine metabolic pathways. Exposure to metal mixtures is mainly associated with alterations in lipid metabolism and amino acid metabolism, particularly in the glycerophospholipid and arginine and proline metabolism pathways.