Analytical aspects of meet-in-metabolite analysis for molecular pathway reconstitution from exposure to adverse outcome

Abstract

To explore the etiology of diseases is one of the major goals in epidemiological study. Meet-in-metabolite analysis reconstitutes biomonitoring-based adverse outcome (AO) pathways from environmental exposure to a disease, in which the chemical exposome-related metabolism responses are transmitted to incur the AOrelated metabolism phenotypes. However, the ongoing data-dependent acquisition of non-targeted biomonitoring by high-resolution mass spectrometry (HRMS) is biased against the low abundance molecules, which forms the major of molecular internal exposome, i.e., the totality of trace levels of environmental pollutants and/or their metabolites in human samples. The recent development of data-independent acquisition protocols for HRMS screening has opened new opportunities to enhance unbiased measurement of the extremely low abundance molecules, which can encompass a wide range of analytes and has been applied in metabolomics, DNA, and protein adductomics.In addition, computational MS for small molecules is urgently required for the topdown exposome databases. Although a holistic analysis of the exposome and endogenous metabolites is plausible, multiple and flexible strategies, instead of "putting one thing above all" are proposed.

Current Evidence: Application of Metabolomic Approaches to Reveal Toxic Effect of Chemicals and Herbal Medicines

“…45 Although this methods cover a wide range of compounds, they are particularly insensitive to low abundance metabolites. 46,47 Naringenin is a flavonoid compound found isolated from Citrus sinensis (var. Valencia) peels, which can improve CCl 4 -induced liver toxicity.…”

Molecular aspects of exposome and metabolic diseases

“…A central point in the type of studies that are needed for a better understanding of the effects of the exposome in humans is reconstituting signalling pathways from the exposure to harmful exposome to the adverse outcome, as highlighted in the review by Hequing Shen and colleagues (Shen et al, 2022). Exposome is the measure of all exposures of an individual in a lifetime, and how the exposures relate to disease and how to accurately measure their effect on human health is of crucial importance.…”