Integrated exposomics/metabolomics for rapid exposure and effect analyses

Environmental drivers of disease susceptibility, referred to as the exposome in its totality, are poorly understood. Measuring the myriad of chemicals that humans are exposed to is immensely challenging and identifying disrupted metabolic pathways is an even more complex task. Here, we present a novel technological approach for the comprehensive, rapid and integrated analysis of the endogenous human metabolome and the chemical exposome. By combining reverse-phase and hydrophilic interaction liquid chromatography and fast polarity switching, molecules with highly diverse chemical structures can be analyzed in 15 minutes with a single analytical run. Standard reference materials and authentic standards were evaluated to critically benchmark performance. Highly sensitive median limits of detection with 0.04 µM for >140 quantitatively assessed endogenous metabolites and 0.08 ng/mL for the >100 model xenobiotics were obtained. To prove the dual-column approach’s applicability, real-life samples from sub-Saharan Africa (high exposure scenario) and Europe (low exposure scenario) were assessed in a targeted and non-targeted manner. Our LC-HRMS approach demonstrates the feasibility to quantitatively and simultaneously assess the endogenous metabolome and the chemical exposome for the high-throughput measurement of environmental drivers of disease.