Integrated Exposomics/Metabolomics for Rapid Exposure and Effect Analyses

The totality of environmental
exposures and lifestyle factors,
commonly referred to as the exposome, is 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 (HILIC) and fast polarity-switching,
molecules with highly diverse chemical structures can be analyzed
in 15 min 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 (LODs) 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 nontargeted manner. Our
liquid chromatography high-resolution mass spectrometry (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 diseases.