Metabolic Signatures of the Exposome—Quantifying the Impact of Exposure to Environmental Chemicals on Human Health

Abstract

Human health and well-being are intricately linked to environmental quality. Environmental exposures can have lifelong consequences. In particular, exposures during the vulnerable fetal or early development period can affect structure, physiology and metabolism, causing potential adverse, often permanent, health effects at any point in life. External exposures, such as the “chemical exposome” (exposures to environmental chemicals), affect the host’s metabolism and immune system, which, in turn, mediate the risk of various diseases. Linking such exposures to adverse outcomes, via intermediate phenotypes such as the metabolome, is one of the central themes of exposome research. Much progress has been made in this line of research, including addressing some key challenges such as analytical coverage of the exposome and metabolome, as well as the integration of heterogeneous, multi-omics data. There is strong evidence that chemical exposures have a marked impact on the metabolome, associating with specific disease risks. Herein, we review recent progress in the field of exposome research as related to human health as well as selected metabolic and autoimmune diseases, with specific emphasis on the impacts of chemical exposures on the host metabolome.

Precision environmental health monitoring by longitudinal exposome and multi-omics profiling

“…Moreover, certain high-degree metabolic pathways were involved in both protein and immune-related pathways, such as alanine aspartate and glutamate metabolism, protein digestion and absorption, and beta-alanine metabolism. Specifically, specific protein metabolism pathways (e.g., amino acids synthesis and protein breakdown) were highly sensitive to oxidative stresses caused by the exposome components ( Peters et al 2021 ); inflammation is often the first immunological response to foreign substances; and the kidney and liver are the main detoxification organs ( Peters et al 2021 ), with liver and bile acids serving essential roles in responding to the foreign substances ( Orešič et al 2020 ).…”

Data Processing Thresholds for Abundance and Sparsity and Missed Biological Insights in an Untargeted Chemical Analysis of Blood Specimens for Exposomics

“…Similarly, untargeted chemical analyses using a high-resolution LC/MS instrument can detect thousands of small molecules in bio-fluid samples and can generate high quality and rich semi-quantitative data to identify and discover new metabolic hypotheses, biomarkers, and risk factors for diseases and biological phenotypes (16)(17)(18)(19)(20). In contrast to a targeted assay (21), an untargeted assay aims to detect in an unbiased manner as many possible chemicals present in a bio-fluid sample using a GC/LC-HRMS instrument (18) and such untargeted assays are key methods in exposome research to identify and discover new risk factors and biomarkers for chronic diseases (21)(22)(23).…”

Precision environmental health monitoring by longitudinal exposome and multi-omics profiling

“…Moreover, certain high-degree metabolic pathways are both protein and immune-related pathways, such as alanine aspartate and glutamate metabolism, protein digestion and absorption, and beta-alanine metabolism. Specifically, particular protein metabolisms (e.g., amino acids synthesis and protein breakdown) were highly sensitive to oxidative stresses caused by the exposome components 46 , inflammation is often the first immunological response to foreign substances, and kidneys and liver are the main detoxification organs 46 , with liver and bile acids serving essential roles in responding to the foreign substances 47 . To further investigate the health effects of the exposome, we performed Spearman correlation analysis with cytokines and blood test results.…”