Integrated Exposomics/Metabolomics for Rapid Exposure and Effect Analyses

Mira Flasch, Veronika Fitz, Evelyn Rampler, Chibundu N. Ezekiel, Gunda Koellensperger, Benedikt Warth (Corresponding author)

Publications: Contribution to journalArticlePeer Reviewed

Abstract

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.
Original languageEnglish
Pages (from-to)2548-2560
Number of pages13
JournalJACS Au
Volume2
Issue number11
DOIs
Publication statusPublished - Nov 2022

Austrian Fields of Science 2012

  • 106057 Metabolomics
  • 104002 Analytical chemistry

Keywords

  • exposome
  • metabolome
  • human biomonitoring
  • high-resolution mass spectrometry
  • exposure
  • biomarker
  • PHTHALATE EXPOSURE
  • MASS-SPECTROMETRY
  • BISPHENOL-A
  • EXPOSOME
  • METABOLOMICS
  • COVERAGE
  • URINE
  • BLOOD

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