Non-targeted metabolomics and associations with per- and polyfluoroalkyl substances (PFAS) exposure in humans: A scoping review

Guo, Pengfei; Furnary, Tristan; Vasiliou, Vasilis; Qi, Yan; Nyhan, Kate; Jones, Dean P.; Johnson, Caroline H.; Liew, Zeyan

doi:10.1016/j.envint.2022.107159

Cited by 55 publications

(35 citation statements)

References 137 publications

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“…Although we intended to summarise the common and overlapping omic features or pathways associated with speci c EDCs from the articles we reviewed, the comparison of results across different studies is challenging due to the small overlap across studies in omic matrices, omics coverage/techniques, study populations, statistical approaches, and potential confounders used as adjustment factors. In addition, there is considerable heterogeneity in the reporting of results, as highlighted in a previous review focusing on PFASs and metabolomics (Guo, 2022). This was particularly true for non-targeted studies that provided hypothesis driven results interpretation: even studies that published all associations in the supplement, showed only results that were relevant for the health outcome or target tissue of interest, in the main text.…”

Section: Main Ndingsmentioning

confidence: 99%

“…Only a few reviews have covered the topic of omics application in human populations and chemical exposures, focusing on general early life environmental exposures (e.g. smoking, toxic metals, air pollution (Everson & Marsit, 2018)), per uorinated compounds (PFASs) and metabolomics (Guo, 2022) or multiple chemicals (S. Kim et al, 2022) but none focused on EDCs and multi-omics.…”

Section: Introductionmentioning

confidence: 99%

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Integrating -omics approaches into population-based studies of endocrine disrupting chemicals: a scoping review

Maitre

Jedynak

Gallego³

et al. 2022

Preprint

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Health effects of endocrine disrupting chemicals (EDCs) are challenging to detect in the general population. Omics technologies become increasingly common to identify early biological changes before the apparition of clinical symptoms, to explore toxic mechanisms and to increase biological plausibility of epidemiological associations. This scoping review systematically summarises the application of omics in epidemiological studies assessing EDCs-associated biological effects to identify potential gaps and priorities for future research. Ninety-eight human studies (2004–2021) were identified through database searches (PubMed, Scopus) and citation chaining and focused on phthalates (34 studies), phenols (19) and PFASs (17), while PAHs (12) and recently-used pesticides (3) were less studied. The sample sizes ranged from 10 to 12,476 (median = 159), involving non-pregnant adults (38), pregnant women (11), children/adolescents (15) or both populations studied together (23). Several studies included occupational workers (10) and/or highly exposed groups (11) focusing on PAHs, PFASs and pesticides, while studies on phenols and phthalates were performed in the general population only. Analysed omics layers included metabolic profiles (30, including 14 targeted analyses), miRNA (13), gene expression (11), DNA methylation (8), microbiome (5) and proteins (3). Twenty-one studies implemented targeted multi-assays focusing on clinical routine blood lipid traits, oxidative stress or hormones. Overall, DNA methylation and gene expression associations with EDCs did not overlap across studies, while some EDC-associated metabolite groups, such as carnitines, nucleotides and amino acids in untargeted metabolomic studies, and oxidative stress markers through targeted studies were consistent across studies. Studies had common limitations such as small sample sizes, cross-sectional designs and single sampling for exposure biomonitoring. In conclusion, there is a growing body of evidence evaluating the early biological responses to exposure to EDCs. This review points to a need for larger longitudinal studies, wider coverage of exposures and biomarkers, replication studies and standardisation of research methods and reporting.

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Section: Main Ndingsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrating -omics approaches into population-based studies of endocrine disrupting chemicals: a scoping review

Maitre

Jedynak

Gallego³

et al. 2022

Preprint

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“…Although previous studies have used metabolomics to examine the associations of PFAS exposure and alterations in metabolic pathways, important gaps in the literature remain. 25 In vivo and in vitro models have shown that exposure to individual PFAS alters fatty acid metabolism, including in human cell lines, 26 rodents, 27 – 29 and zebrafish. 30 In humans, studies using both targeted and untargeted metabolomics methods have reported similar associations between exposure to individual PFAS, including PFOS, PFHxS, and PFOA, and fatty acid metabolism.…”

Section: Introductionmentioning

confidence: 99%

“… 48 Previous studies examining the impact of PFAS mixtures on the metabolome have relied primarily on reducing the dimensionality of the correlated PFAS exposures prior to analysis using either principal components or by calculating the sum of PFAS congeners. 25 However, it is difficult to draw conclusions about the effects of different components of the PFAS mixture from these studies owing to difficulties in interpreting principal components or summed exposure variables. Despite the analytical difficulties, examining the effects of PFAS mixtures on metabolic pathways is key to fully understand the consequences of exposure to these chemicals.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Signatures of Youth Exposure to Mixtures of Per- and Polyfluoroalkyl Substances: A Multi-Cohort Study

Goodrich

Walker

et al. 2023

Environ Health Perspect

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Background: Exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous and has been associated with an increased risk of several cardiometabolic diseases. However, the metabolic pathways linking PFAS exposure and human disease are unclear. Objective: We examined associations of PFAS mixtures with alterations in metabolic pathways in independent cohorts of adolescents and young adults. Methods: Three hundred twelve overweight/obese adolescents from the Study of Latino Adolescents at Risk (SOLAR) and 137 young adults from the Southern California Children’s Health Study (CHS) were included in the analysis. Plasma PFAS and the metabolome were determined using liquid-chromatography/high-resolution mass spectrometry. A metabolome-wide association study was performed on log-transformed metabolites using Bayesian regression with a g-prior specification and g-computation for modeling exposure mixtures to estimate the impact of exposure to a mixture of six ubiquitous PFAS (PFOS, PFHxS, PFHpS, PFOA, PFNA, and PFDA). Pathway enrichment analysis was performed using Mummichog and Gene Set Enrichment Analysis. Significance across cohorts was determined using weighted -tests. Results: In the SOLAR and CHS cohorts, PFAS exposure was associated with alterations in tyrosine metabolism (meta-analysis ) and de novo fatty acid biosynthesis ( ), among others. For example, when increasing all PFAS in the mixture from low ( th percentile) to high ( th percentile), thyroxine (T4), a thyroid hormone related to tyrosine metabolism, increased by 0.72 standard deviations (SDs; equivalent to a standardized mean difference) in the SOLAR cohort (95% Bayesian credible interval (BCI): 0.00, 1.20) and 1.60 SD in the CHS cohort (95% BCI: 0.39, 2.80). Similarly, when going from low to high PFAS exposure, arachidonic acid increased by 0.81 SD in the SOLAR cohort (95% BCI: 0.37, 1.30) and 0.67 SD in the CHS cohort (95% BCI: 0.00, 1.50). In general, no individual PFAS appeared to drive the observed associations. Discussion: Exposure to PFAS is associated with alterations in amino acid metabolism and lipid metabolism in adolescents and young adults. https://doi.org/10.1289/EHP11372

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“…Usually, investigation of metabolic-related toxicity induced by emerging pollutants focuses on dysregulated endogenous metabolites, such as amino acids, fatty acids, saccharides and lipids. [19][20][21][22][23] As a class of endogenous metabolites, phospholipids have been acknowledged to play the crucial role in biochemical processes in organisms. For example, phospholipids are the main components of membranes, energy storage molecules and signaling molecules.…”

Section: Introductionmentioning

confidence: 99%

Internal extractive electrospray ionization mass spectrometry for investigating the phospholipid dysregulation induced by perfluorooctanoic acid in Nile tilapia

Liu

Lu²,

Ning

et al. 2022

Analyst

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Non-targeted metabolomics and associations with per- and polyfluoroalkyl substances (PFAS) exposure in humans: A scoping review

Cited by 55 publications

References 137 publications

Integrating -omics approaches into population-based studies of endocrine disrupting chemicals: a scoping review

Integrating -omics approaches into population-based studies of endocrine disrupting chemicals: a scoping review

Metabolic Signatures of Youth Exposure to Mixtures of Per- and Polyfluoroalkyl Substances: A Multi-Cohort Study

Internal extractive electrospray ionization mass spectrometry for investigating the phospholipid dysregulation induced by perfluorooctanoic acid in Nile tilapia

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