Metabolomic signatures of lead exposure in the VA Normative Aging Study

Kelly, Rachel S.; Bayne, Haley; Spiro, Avron; Vokonas, Pantel; Sparrow, David; Weiss, Scott T.; Schwartz, Joel; Nassan, Feiby L.; Lee-Sarwar, Kathleen; Huang, Mengna; Kachroo, Priyadarshini; Chu, Su H.; Litonjua, Augusto A.; Lasky‐Su, Jessica

doi:10.1016/j.envres.2020.110022

Cited by 25 publications

(39 citation statements)

References 47 publications

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“…Participants (N = 456) provided 648 blood samples in which 1158 distinct metabolites were quantified and passed our in-house QC pipeline [30,31]. Approximately 64% of the participants provided one blood sample, 31% provided two samples, and 6% provided three samples.…”

Section: Resultsmentioning

confidence: 99%

“…Metabolites were identified by their mass-to-charge ratio, retention time, and through a comparison to a library of purified known standards. Metabolites were quantified using area-under-the-curve (AUC) of the peak and processed according to our in-house standard quality control pipeline [30,31] which retains the maximum number of metabolites, including those with a high level of missingness as these may represent biologically important markers of exposure in a subset of the population, while excluding statistically uninformative metabolites. Missing values were imputed with half of the minimum observed level for a given metabolite [31].…”

Section: Metabolomic Profiling (Outcomes)mentioning

confidence: 99%

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Metabolomic signatures of the long-term exposure to air pollution and temperature

et al. 2021

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Background Long-term exposures to air pollution has been reported to be associated with inflammation and oxidative stress. However, the underlying metabolic mechanisms remain poorly understood. Objectives We aimed to determine the changes in the blood metabolome and thus the metabolic pathways associated with long-term exposure to outdoor air pollution and ambient temperature. Methods We quantified metabolites using mass-spectrometry based global untargeted metabolomic profiling of plasma samples among men from the Normative Aging Study (NAS). We estimated the association between long-term exposure to PM2.5, NO2, O3, and temperature (annual average of central site monitors) with metabolites and their associated metabolic pathways. We used multivariable linear mixed-effect regression models (LMEM) while simultaneously adjusting for the four exposures and potential confounding and correcting for multiple testing. As a reduction method for the intercorrelated metabolites (outcome), we further used an independent component analysis (ICA) and conducted LMEM with the same exposures. Results Men (N = 456) provided 648 blood samples between 2000 and 2016 in which 1158 metabolites were quantified. On average, men were 75.0 years and had an average body mass index of 27.7 kg/m2. Almost all men (97%) were not current smokers. The adjusted analysis showed statistically significant associations with several metabolites (58 metabolites with PM2.5, 15 metabolites with NO2, and 6 metabolites with temperature) while no metabolites were associated with O3. One out of five ICA factors (factor 2) was significantly associated with PM2.5. We identified eight perturbed metabolic pathways with long-term exposure to PM2.5 and temperature: glycerophospholipid, sphingolipid, glutathione, beta-alanine, propanoate, and purine metabolism, biosynthesis of unsaturated fatty acids, and taurine and hypotaurine metabolism. These pathways are related to inflammation, oxidative stress, immunity, and nucleic acid damage and repair. Conclusions Using a global untargeted metabolomic approach, we identified several significant metabolites and metabolic pathways associated with long-term exposure to PM2.5, NO2 and temperature. This study is the largest metabolomics study of long-term air pollution, to date, the first study to report a metabolomic signature of long-term temperature exposure, and the first to use ICA in the analysis of both.

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Section: Resultsmentioning

confidence: 99%

Section: Metabolomic Profiling (Outcomes)mentioning

confidence: 99%

Metabolomic signatures of the long-term exposure to air pollution and temperature

et al. 2021

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“…Another epidemiologic analysis in the Veterans Administration Normative Aging Study found several blood metabolites associated with blood Pb, including amino acids, lipids, and metabolites involved in oxidative stress and immune pathways (13). Taken together, these results indicate that biologically-relevant metabolic changes occur with Pb exposure.…”

Section: Introductionmentioning

confidence: 83%

Lead exposure and serum metabolite profiles in pregnant women in Mexico City

Niedzwiecki

Eggers

Joshi

et al. 2021

Preprint

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Background: Lead (Pb) exposure is a global health hazard causing a wide range of adverse health outcomes. Yet, the mechanisms of Pb toxicology remain incompletely understood, especially during pregnancy. To uncover biological pathways impacted by Pb exposure, this study investigated serum metabolomic profiles during the third trimester of pregnancy that are associated with blood Pb and bone Pb. Methods: We used data and specimens collected from 99 women enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort based in Mexico City. Maternal Pb exposure was measured in whole blood samples from the third trimester of pregnancy and in the tibia and patella bones at 1 month postpartum. Third-trimester serum samples underwent metabolomic analysis; metabolites were identified based on matching to an in-house analytical standard library. A metabolome-wide association study was performed with all three Pb measurements using multiple linear regression models, adjusted for confounders and batch effects. Class enrichment analyses were also conducted. Results: The median (interquartile range) blood Pb concentration was 2.9 (2.6) μg/dL. Median bone Pb, measured in the patella and tibia, were 2.5 (7.3) μg/g and 3.6 (9.5) μg/g, respectively. Of 248 total metabolites identified in serum, 31 were associated with blood Pb (p<0.05). Class enrichment analysis identified significant overrepresentation of metabolites classified as fatty acids and conjugates, amino acids and peptides, and purines. Tibia and patella Pb were associated with 14 and 11 metabolites, respectively (p<0.05). Comparing results from bone and blood Pb, glycochenodeoxycholic acid and glycocholic acid were negatively associated with blood Pb and tibia Pb, while 5-aminopentanoic acid and 7-methylguanine were negatively associated with blood Pb and patella Pb. One metabolite, 5-aminopentanoic acid, was associated with all three Pb measures. Conclusion: This study identified serum metabolites in pregnant women associated with Pb measured in blood (31 metabolites) and bone (tibia: 14 metabolites, patella: 11 metabolites). These findings provide insights on the metabolic profile around Pb exposure in pregnancy and may provide important links to guide detailed studies of toxicological effects for both mothers and children.

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“…Current metabolomics studies using epidemiological data such as those described in Section 5.1.1 already provide insight into the metabolic fingerprints associated with certain chemical hazards, although their specificity has yet to be demonstrated. Several examples can be found in the literature on effect biomarkers discovered by human metabolomics that may be related to metabolic fingerprints characteristic of specific chemical hazards such as lead [176] or TCDD [97], or more generally, with exposure to complex pesticide mixtures [177].…”

Section: Metabolic Fingerprints For Exposure Assessmentmentioning

confidence: 99%

Metabolomics in chemical risk analysis – A review

Hernández‐Mesa

Bizec

2021

Analytica Chimica Acta

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Food safety has become a major issue worldwide and, in particular, detecting the presence of toxins, contaminants or residues of chemical substances along the food chain and in fine in foods constitutes a strong consumers demand. In general, all these substances and the corresponding metabolites of interest are analyzed using efficient targeted methodologies. However, in some cases these targeted approaches do not allow the detection of emerging compounds or practices, and therefore new approaches and strategies are required. Thus, the study of physiological perturbations induced by exposure to a given chemical substance has emerged as an interesting alternative approach to apply in chemical food safety.This review focuses on describing significant applications of metabolomics in the field of risk analysis from a chemical food safety perspective. The different risk assessment steps, including hazard identification, doseresponse assessment and exposure assessment, and risk management are addressed through various examples to illustrate that such an approach is fit-for-purpose and meets the expectations and requirements of chemical risk analysis. It can be considered as an innovative tool for predicting the probable occurrence and nature of risks, while addressing the current challenges of chemical risk analysis (e.g. replacement, reduction and refinement (3R) of animal testing, effects of exposure to chemical mixtures at low doses, etc.), and with the aim of responding to global food safety issues and anticipating human health problems.

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Metabolomic signatures of lead exposure in the VA Normative Aging Study

Cited by 25 publications

References 47 publications

Metabolomic signatures of the long-term exposure to air pollution and temperature

Metabolomic signatures of the long-term exposure to air pollution and temperature

Lead exposure and serum metabolite profiles in pregnant women in Mexico City

Metabolomics in chemical risk analysis – A review

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