Deployment-Associated Exposure Surveillance With High-Resolution Metabolomics

Abstract

Objective: The aim of this study was to assess the suitability of high-resolution metabolomics (HRM) for measure of internal exposure and effect biomarkers from deployment-related environmental hazards.

Methods: HRM provides extensive coverage of metabolism and data relevant to a broad spectrum of environmental exposures. This review briefly describes the analytic platform, workflow, and recent applications of HRM as a prototype environmental exposure surveillance system.

Results: Building upon techniques available for contemporary occupational medicine and exposure sciences, HRM methods are able to integrate external exposures, internal body burden of environmental agents, and relevant biological responses with health outcomes.

Conclusions: Systematic analysis of existing Department of Defense Serum Repository samples will provide a high-quality, cross-sectional reference dataset for deployment-associated exposures while at the same time establishing a foundation for precision medicine.

Figure 1

High-resolution MS supports untargeted measurement of metabolic chemicals by reducing requirements for chemical separation and sample preparation while providing improved capability to measure low abundance chemicals in biological samples (14). Used with copyright permission from Annual Review of Nutrition.

Figure 2

HRM profiling of plasma obtained from healthy individuals has indicated that metabolic intermediates from >80% of pathways present in the KEGG database can be detected (represented by black dots) using standardized sample preparation methods and dual-column chromatography.

Figure 3

While a core metabolome consisting of metabolites required for life will be detected universally, environmental, drug and dietary chemicals in the metabolic profile are expected to vary greatly in concentration and presence. Adapted from (45).

Figure 4

Cross-platform comparison of targeted polycyclic aromatic hydrocarbon (PAH) measurements using gas chromatography MS and suspect screening for PAH metabolites by HRM (A). Combining liquid chromatography and ionizations schemes maximized coverage of PAH metabolism (B).

Figure 5

A targeted metabolome wide association study (MWAS) was completed by testing each metabolite for significant associations with triethylphosphate levels in plasma. Significant metabolites can be tested for pathway enrichment, providing a starting point in identifying perturbations linked to chemical exposure.

Figure 6

HRM profiling of specimens collected from active duty individuals could readily be integrated into DoDSR protocols. In this example, HRM can evaluate the presence of exposure and effect biomarkers, identifying individuals at risk for exposure related diseases. Adapted from (45).

Figure 7

Microbiome-MWAS of bronchoalveolar lavage fluid in HIV-1: A to C represent increasing stringency to identify network associations with greatest r meeting significance criteria. D to F contains the network subset associated with HIV-1, in order of increasing leniency. From (86).