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The preliminary investigation of potential response biomarkers to PAHs exposure on childhood asthma

Journal of Exposure Science & Environmental Epidemiology volume 32, pages 82–93 (2022)Cite this article

Abstract

Background

Exposure to polycyclic aromatic hydrocarbons (PAHs) is a potential risk factor for asthma prevalence. This study aims to explore whether PAHs exposure is associated with childhood asthma by altering microbial diversity and metabolic profiles.

Methods

Thirty children with asthma and 30 children as control in Nanjing, China were recruited. Urinary 1-hydroxypyrene (1-OHPyr) level was determined by UPLC–Orbitrap–MS as a PAHs exposure biomarker. Logistic regression was conducted to investigate the association between 1-OHPyr and childhood asthma. Microbial diversity was analyzed by 16S rRNA gene sequencing. Metabolic profiles were obtained by UPLC–Orbitrap–MS methods. Differential microbiota and metabolites were screened and selected as response biomarkers or intermediates. Mediation analysis was conducted to assess the association between PAHs and asthma mediated by intermediates.

Results

Participating children with and without asthma aged 6.43 ± 2.23 years. The urinary 1-OHPyr level ranged from 0.10 to 1.51 μmol/mol (creatinine corrected) in the participants. The urinary 1-OHPyr level was associated with childhood asthma (OR = 7.21, 95% CI: 1.03–50.42 per 1 μmol/mol unit). Microbial diversity was decreased in the group with asthma and there was a significant shift in the abundance of Proteobacteria (at the phylum level), Veillonella and Prevotella (at the genus level). The enrichment pathway analysis showed that differentially expressed metabolites were involved in purine metabolism, amino acid metabolism, and lipid and fatty acid metabolism. The urinary 1-OHPyr level was associated with the abundance of Actinomyces sp. oral clone IO076 and 7-methylguanine that showed a mediation effect on the association between urinary 1-OHPyr levels and childhood asthma by mediation analysis.

Conclusions

Urinary 1-OHPyr exposure was associated with childhood asthma, microbial diversity, and metabolic profiles. Microbial diversity and metabolic profiles may be intermediates as response biomarkers to PAHs exposure in childhood asthma. Further research is needed to confirm these study results and determine the underlying mechanism.

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Fig. 1: The microbial diversity indices of the group with asthma and the control.
Fig. 2: Microbial community compositions at the phylum and genus levels.
Fig. 3: The comparison of microbial communities between the group with asthma and the control using the Wilcoxon rank-sum test.
Fig. 4: The different 16S rRNA OTUs enriched on the detailed KEGG pathway analyses.
Fig. 5: The score plot from PLS-DA model of UPLC–Orbitrap–MS datasets distinguishing between the group with asthma and the control.
Fig. 6: The differential metabolites involved in purine metabolic pathways compared with the control group.
Fig. 7: Mediation analysis of the association between urinary 1-OHPyr levels and childhood asthma by microbiota and metabolites.

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Funding

This work was supported by the National Natural Science Foundation of China (82073630, 81728018, and 81530088), Natural Science Foundation of Jiangsu Province (BK20161571), Natural Science Foundation of the Higher Education Institution of Jiangsu Province (16KJA330002), and the open project of the key laboratory of Modern Toxicology of Ministry Education Nanjing Medical University (NMUAMT201802). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Author notes

  1. These authors contributed equally: Jinye Hu, Yuling Bao

Authors and Affiliations

  1. The Key Laboratory of Modern Toxicology of Ministry of Education and Department of Health Inspection and Quarantine, Nanjing Medical University, Nanjing, China

    Jinye Hu, Zhan Zhang, Lei Li & Qian Wu

  2. Department of Respiratory, Children’s Hospital of Nanjing Medical University, Nanjing, China

    Yuling Bao

  3. Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China

    Hui Huang & Feng Chen

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Contributions

Conceptualization: LL and QW; formal analysis: JH and YB; funding acquisition: FC and QW; investigation: JH; resources: YB, ZZ, FC, and LL; and writing original draft: QW.

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Correspondence to Lei Li or Qian Wu.

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The authors declare no competing interests.

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The Nanjing Medical University Clinical Research Ethics Committee, Nanjing, China, reviewed and approved the protocols of this study. Written informed consent was obtained from the participants’ parents for the use of samples in this study.

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Hu, J., Bao, Y., Huang, H. et al. The preliminary investigation of potential response biomarkers to PAHs exposure on childhood asthma. J Expo Sci Environ Epidemiol 32, 82–93 (2022). https://doi.org/10.1038/s41370-021-00334-4

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