Analytical challenges in human exposome analysis with focus on environmental analysis combined with metabolomics

Abstract

Environmental factors, such as chemical exposures, are likely to play a crucial role in the development of several human chronic diseases. However, how the specific exposures contribute to the onset and progress of various diseases is still poorly understood. In part, this is because comprehensive characterization of the chemical exposome is a highly challenging task, both due to its complex dynamic nature as well as due to the analytical challenges. Herein, the analytical challenges in the field of exposome research are reviewed, with specific emphasis on the sampling, sample preparation, and analysis, as well as challenges in the compound identification. The primary focus is on the human chemical exposome, that is, exposures to mixtures of environmental chemicals and its impact on human metabolome. In order to highlight the recent progress in the exposome research in relation to human health and disease, selected examples of human exposome studies are presented.

Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective

“…Considering the complexity of the chemical exposome, it is unlikely that there will soon be a single untargeted method capable of capturing the full range of small molecules that are present in biofluids or environmental samples. 98 In a review of the human blood exposome by Rappaport et al, 17 the concentrations of 94 known pollutants, 49 drugs, 195 food chemicals, and 1223 endogenous chemicals spanned 11 orders of magnitude in blood, from 160 fM to 140 mM. 17 Considering that modern mass spectrometers are at best linear over 5−6 orders of magnitude, several types of unbiased sample extractions and untargeted analytical methods will be required to achieve detection and semiquantification for a comprehensive profile of small molecules in human blood.…”

“…17 Considering that modern mass spectrometers are at best linear over 5−6 orders of magnitude, several types of unbiased sample extractions and untargeted analytical methods will be required to achieve detection and semiquantification for a comprehensive profile of small molecules in human blood. 98 Untargeted high-resolution metabolomics analysis, based on liquid chromatography (LC) and HRMS has been proposed for "sequencing the exposome", 38 but clearly, a wider range of instrumental approaches will be required. This can be exemplified by considering the wide range of organic contaminants routinely monitored in human blood by target methods (Figure 2).…”

“…Considering the complexity of the chemical exposome, it is unlikely that there will soon be a single untargeted method capable of capturing the full range of small molecules that are present in biofluids or environmental samples . In a review of the human blood exposome by Rappaport et al, the concentrations of 94 known pollutants, 49 drugs, 195 food chemicals, and 1223 endogenous chemicals spanned 11 orders of magnitude in blood, from 160 fM to 140 mM .…”

Machine learning for screening active metabolites with metabolomics in environmental science

“…5 With the rapid development of a range of analytical instrumentals, such as liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), capillary electrophoresis-mass spectrometry (CE-MS), and nuclear magnetic resonance spectroscopy (NMR), metabolomics techniques enable the separation, detection, and quantitation of a wide range of metabolites and their associated biochemical metabolic pathways. 6 Due to the diverse properties of metabolites, a combination of analytical techniques is required to detect all metabolites in biological samples, facilitating increased metabolite coverage. Advanced analytical techniques generate large volumes of highly sensitive and highresolution metabolomics data, combined with new data analysis strategy approaches, allowing the identication of complex metabolites and the annotation of physiological and pathological phenomena arising from environmental stress 7,8 (Fig.…”

Lipidomics profiling of zebrafish liver through untargeted liquid chromatography‐high resolution mass spectrometry

“…The most commonly used lipidomics strategy consists of extraction using organic solvents, followed by reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) [5,7]. Untargeted high-resolution MS (HRMS) methods combined with liquid-liquid extraction (LLE) provide comprehensive coverage of multiple lipid classes [1,8]. In many applications, sample preparation methods developed for a specific sample type will be applied to a different matrix.…”