Analyzing Specific Research Ideas on Environmental Exposure Metabolome

In our previous piece, we highlighted diverse environmental exposures and their correlated metabolic profiles. This continuation delves deeper into specific research concepts associated with environmental exposure. We present three instances of multi-omics studies on environmental exposure, focusing on metabolomic investigations.

Phenotyping + Metabolome

In the article "Metabolomics analysis explores the rescue to neurobehavioral disorder induced by maternal PM2.5 exposure in mice (DOI: 10.1016/j.ecoenv.2018.11.037)," researchers delved into the reproductive epidemiology linking perinatal PM2.5 exposure to adverse birth outcomes. To explore this impact, pregnant rats at 1.5 days of gestation were exposed to PM2.5 or clean air for 14 consecutive days (12 rats per group). Phenotypic analysis revealed no significant differences in mortality, body weight, live fetus count, or offspring development between control and exposed groups. However, neurobehavioral tests indicated significantly heightened spontaneous movement and exploratory behavior in the offspring of the PM2.5-exposed group. Metabolomic analysis unveiled activation of the dopamine pathway and inhibition of the glycine pathway in the exposed mice's brains. Administering a DRD4 antagonist or supplementing the mouse offspring with the glycine receptor agonist taurine alleviated the observed hypermobility. These findings suggest that maternal air pollution exposure during critical brain development may elevate the risk of neurological disorders in offspring.

Phenotyping + Metabolome + Microbiome

The study titled "Impact of Heavy Metal Exposure on the Gut Microbiome and Metabolites Associated with Metabolic Health (DOI: 10.1007/s12011-021-03092-4)" investigated the association of cadmium and arsenic exposure with metabolic health issues through epidemiological and animal studies. To investigate their effects, mice underwent exposure to 50 ppm cadmium and 50 ppm arsenic for 2 weeks, followed by colon content sequencing for 16S rRNA amplicons and cecum content sequencing for metabolomics. Phenotypic analysis demonstrated no significant differences in body weight, food, or water consumption between control and exposed groups. Microbiome analysis revealed reduced gut microbial diversity induced by both metals, especially pronounced in the cadmium-exposed group. Alterations were observed in several genera, including butyric acid-producing bacteria. Metabolomics showed significant disruptions in overall metabolome, particularly prominent in the cadmium-exposed group, with distinct differences in bile acid-associated molecules. Network analysis identified genera with significant variations in metabolite interactions, including Brautella spp, Eisenbergia spp, and Clostridium difficile_XlVa. These findings suggest that cadmium and arsenic exposure alter the gut microbiome and metabolome, influencing bile acids, amino acids, and metabolic health-related flora.

Phenotyping + Metabolome + Proteome

The article 'Integration of proteomics and metabolomics reveals promotion of proliferation by exposure of bisphenol S in human breast epithelial MCF-10A cells (DOI: 10.1016/j.scitotenv.2019.136453)' has highlighted the potential carcinogenic and hormone-like effects of BPA, a raw material in previous food packaging on epidemiological and animal studies. The assessment of BPS, a structural analog of BPA, is crucial for safety evaluation. MCF-10A cell lines exhibited differing proliferation rates after exposure to various BPS concentrations for 24 hours, as observed in phenotypic analysis combined with MTT assays. Proteomic analysis revealed differential expression of 200 proteins, with increased expression in cell proliferation, EGFR signaling, and metabolic pathway-related proteins after 24h BPS exposure. Metabolomics showed significant differences in 35 endogenous metabolites, mainly associated with purine metabolism, TCA cycle, amino acids, glycerophospholipid, and pyruvate metabolism. Both proteomics and metabolomics indicated BPS-induced promotion of MCF-10A proliferation, upregulation of EGFR receptor expression, cell proliferation-related proteins, and enhancement of metabolic pathways involved in cell proliferation and signaling. These results suggest that low concentrations of BPS exhibit hormone-like effects, promoting cell proliferation through the EGFR-mediated signaling pathway and enhancing metabolic activities related to proliferation, crucial for safety evaluation.

Summary

These studies highlight the power of multi-omics approaches in unraveling the complex interplay between environmental exposures and health outcomes. Further research is crucial to elucidate the underlying mechanisms and develop effective preventive and therapeutic strategies. If you're interested in exploring the potential of metabolomics and other omics platforms in your own environmental research, please contact us for a consultation