Integrated exposomics/metabolomics for rapid exposure and effect analyses

The totality of environmental exposures and lifestyle factors, commonly referred to as the exposome, are poorly understood. Measuring the myriad of chemicals that humans are exposed to is immensely challenging and identifying disrupted metabolic pathways is even more complex. 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 as both column’s effluents are combined before analysis. Standard reference materials and authentic standards were evaluated to critically benchmark performance. Highly sensitive median limits of detection (LOD) with 0.04 µM for >140 quantitatively assessed endogenous metabolites and 0.08 ng/mL for the >100 model xenobiotics and human estrogens in solvent were obtained. In matrix, the median LOD values were higher with 0.7 ng/mL (urine) and 0.5 ng/mL (plasma) for exogenous chemicals. To prove the dual-column approach’s applicability, real-life urine 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 of quantitatively and simultaneously assessing the endogenous metabolome and the chemical exposome for the high-throughput measurement of environmental drivers of disease.