The Key Laboratory of Modern Toxicology of Ministry of Education and Department of Health Inspection and Quarantine, Nanjing Medical University, Nanjing, China.
Department of Respiratory, Children's Hospital of Nanjing Medical University, Nanjing, China.
J Expo Sci Environ Epidemiol. 2022 Jan;32(1):82-93. doi: 10.1038/s41370-021-00334-4. Epub 2021 May 10.
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.
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.
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.
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.
多环芳烃（PAHs）暴露是哮喘患病率的一个潜在危险因素。本研究旨在通过改变微生物多样性和代谢谱来探讨 PAHs 暴露是否与儿童哮喘有关。
在中国南京，招募了 30 名哮喘儿童和 30 名对照儿童。采用 UPLC-Orbitrap-MS 法测定尿 1-羟芘（1-OHPyr）水平作为 PAHs 暴露生物标志物。采用 logistic 回归分析 1-OHPyr 与儿童哮喘的关系。采用 16S rRNA 基因测序分析微生物多样性。采用 UPLC-Orbitrap-MS 方法获得代谢谱。筛选和选择差异微生物群和代谢物作为反应标志物或中间产物。采用中介分析评估 PAHs 与哮喘之间通过中间产物的关联。
患有和不患有哮喘的儿童年龄为 6.43±2.23 岁。参与者的尿 1-OHPyr 水平范围为 0.10 至 1.51μmol/mol（肌酐校正）。尿 1-OHPyr 水平与儿童哮喘有关（OR=7.21，95%CI：1.03-50.42 每 1μmol/mol 单位）。哮喘组微生物多样性降低，变形菌门（门水平）、韦荣球菌属和普雷沃氏菌属（属水平）的丰度有显著变化。富集通路分析显示，差异表达代谢物参与嘌呤代谢、氨基酸代谢以及脂质和脂肪酸代谢。尿 1-OHPyr 水平与放线菌属 sp. oral clone IO076 和 7-甲基鸟嘌呤的丰度相关，通过中介分析显示，7-甲基鸟嘌呤对尿 1-OHPyr 水平与儿童哮喘之间的关联具有中介作用。
尿 1-OHPyr 暴露与儿童哮喘、微生物多样性和代谢谱有关。微生物多样性和代谢谱可能是儿童哮喘中 PAHs 暴露的反应标志物的中间产物。需要进一步的研究来证实这些研究结果并确定潜在的机制。
