Metabolomics: Environmental Exposure Impact on Health Hazards

Rising environmental pollution presents a significant hurdle to sustainable social and economic progress. Studies increasingly underscore that chronic non-communicable diseases result from a blend of environmental exposure (chemical, physical, and biological factors) and genetics. Focusing solely on genetics in disease research has limitations, prompting a surge in the exploration of environmental exposure's role. In recent years, specialists and scholars have progressively emphasized and explored this area. Consequently, research on environmental exposure has gained momentum, garnering heightened attention.

Complementing genomics, exposomics encompasses exposures across life stages from gestation onward, including exogenous sources like pollution, radiation, and diet, and endogenous factors like inflammation or microorganisms. Common exposures, such as particulate matter (PM), polycyclic aromatic hydroxyls (PAHs), heavy metals, and pesticides, infiltrate the human body via food, water, air, or direct skin contact, posing substantial health risks. Understanding the potential impact of these exposures on human health demands a multidisciplinary approach combining epidemiology, molecular biology, and analytical chemistry. Metabolomics, being closely tied to the phenotype, increasingly aids in environmental exposure studies, shedding light on metabolite level alterations due to chemical pollutant exposure.

The link between environmental exposure and metabolomics is intimate. Upon entry, most environmental exposures undergo metabolism, binding with small biomolecules and vying for metabolic substrates, leading to disruptions in the body's metabolic balance. Furthermore, these exposures can influence gene expression, thereby impacting protein translation and eventually altering metabolites. Metabolomics plays a pivotal role in comprehensively detecting in vivo metabolic changes triggered by environmental exposures, elucidating their pathogenic mechanisms.

Metabolic Profiles and their Association with Various Environmental Exposures

Various environmental exposures can profoundly impact human metabolism, disrupting cellular signaling pathways primarily through oxidative stress. Studies reveal distinct metabolic alterations induced by different pollutants, as depicted in the figure below.

Heavy metals and polycyclic aromatic hydrocarbons (PAHs)

PAHs trigger reactive oxygen species (ROS)-mediated oxidative stress, recognized as a potential mode of action. Studies indicate that metabolite level changes induced by arsenic, cadmium, vanadium, PAHs, or complex mixtures signify oxidation: disruptions in the TCA cycle and compromised amino acid metabolism result in mitochondrial dysfunction, hampering energy production. Oxidative or inflammatory processes might contribute to disturbances in lipid metabolism. The subsequent table outlines the metabolic shifts caused by various heavy metals and PAHs.

Persistent organic pollutants (POPs)

POPs, predominantly dioxins and polychlorinated biphenyls (PCBs), and to a lesser extent, organochlorine pesticides (DDE, HCB, and HCH), have been the focus of metabolomics studies. These investigations often reveal dysregulation in cholesterol, steroid metabolism, and bile acid biosynthesis, consistent with AhR mediation and liver injury. Populations exposed to PCBs, DDE, and HCB also display disruptions in lipid metabolism, affecting fatty acids, glycerophospholipids, sphingolipids, and glycerolipids.

Environmental endocrine disruptors

Environmental endocrine disruptors, including certain pesticides, chemicals, plasticizers, and phenolic compounds commonly found in the environment, exert endocrine-disrupting effects on the body. Jordan et al., utilizing metabolomics, observed that nonylphenol (NP) primarily interferes with glucose, lipid, and nucleic acid metabolism at low exposure levels. Di-octyl phthalate (DEHP) impacts glucose and lipid metabolism, while bisphenol base influences glucose and lipid metabolism as well. Bisphenol propane (BPA) also affects glucose metabolism.

Conclusion

Metabolomics provides a promising avenue for understanding how environmental pollution shapes our health at the molecular level, paving the way for targeted interventions and preventive strategie. At Metware Lab in Boston, we offer comprehensive metabolomics, lipidomics, and Multi-omics services related to this research area. These services include:

•  TM Widely-Targeted Metabolomics
•  Untargeted Metabolomics 
•  Quantitative Lipidomics (over 4000 lipids on the panel)
•  Targeted Bile Acid Assay (65 bile acids)
•  Energy Metabolism (targeted assay with 68 metabolites)
•  Amino Acid Targeted Assay (94 metabolomics)
•  Metware Cloud: (Free Data Analysis Cloud platform, no programming required)

References

1. Bonvallot N, David A, Chalmel, Frédéric, et al. Metabolomics as a powerful tool to decipher the biological effects of environmental contaminants in humans [J]. Current Opinion in Toxicology, 2018:S2468202017301390.

2. Chen Y, Wang Z, Xu M, et al. Nanosilver Incurs an Adaptive Shunt of Energy Metabolism Mode to Glycolysis in Tumor and Nontumor Cells [J]. Acs Nano, 2014, 8(6):5813-25.

3. Jeanneret F, Boccard J, Badoud F, et al. Human urinary biomarkers of dioxin exposure: Analysis by metabolomics and biologically driven data dimensionality reduction [J]. Toxicology Letters, 2014, 230(2):234-243.

4. Jordan J, Zare A, Jackson L J, et al. Environmental Contaminant Mixtures at Ambient Concentrations Invoke a Metabolic Stress Response in Goldfish Not Predicted from Exposure to Individual Compounds Alone [J]. Journal of Proteome Research, 2012, 11(2):1133-1143.