This randomized crossover study investigated the metabolic and mRNA alterations associated with exposure to high and low traffic-related air pollution (TRAP) in 50 participants who were either healthy or were diagnosed with chronic pulmonary obstructive disease (COPD) or ischemic heart disease (IHD). For the first time, this study combined transcriptomics and serum metabolomics measured in the same participants over multiple time points (2 h before, and 2 and 24 h after exposure) and over two contrasted exposure regimes to identify potential multiomic modifications linked to TRAP exposure. With a multivariate normal model, we identified 78 metabolic features and 53 mRNA features associated with at least one TRAP exposure. Nitrogen dioxide (NO₂) emerged as the dominant pollutant, with 67 unique associated metabolomic features. Pathway analysis and annotation of metabolic features consistently indicated perturbations in the tryptophan metabolism associated with NO₂ exposure, particularly in the gut-microbiome-associated indole pathway. Conditional multiomics networks revealed complex and intricate mechanisms associated with TRAP exposure, with some effects persisting 24 h after exposure. Our findings indicate that exposure to TRAP can alter important physiological mechanisms even after a short-term exposure of a 2 h walk. We describe for the first time a potential link between NO₂ exposure and perturbation of the microbiome-related pathways.

中文翻译：

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伦敦交通相关空气污染的多组学特征揭示了肠道微生物组相关途径的潜在短期扰动


这项随机交叉研究调查了 50 名健康或被诊断患有慢性肺阻塞性疾病 (COPD) 或缺血性心脏病 (IHD) 的参与者与高和低交通相关空气污染 (TRAP) 暴露相关的代谢和 mRNA 变化。这项研究首次结合了同一参与者在多个时间点（暴露前 2 小时、暴露后 2 小时和 24 小时）和两种对比暴露方案中测量的转录组学和血清代谢组学，以确定与 TRAP 暴露相关的潜在多组学修饰。通过多变量正常模型，我们确定了与至少一次 TRAP 暴露相关的 78 个代谢特征和 53 个 mRNA 特征。二氧化氮 (NO ₂ ) 成为主要污染物，具有 67 种独特的相关代谢组学特征。代谢特征的通路分析和注释一致表明，色氨酸代谢中存在与 NO ₂ 暴露相关的扰动，特别是在肠道微生物组相关的吲哚通路中。条件多组学网络揭示了与 TRAP 暴露相关的复杂机制，某些影响在暴露后 24 小时持续存在。我们的研究结果表明，即使在短期步行 2 小时后，暴露于 TRAP 也可以改变重要的生理机制。我们首次描述了 NO ₂ 暴露与微生物组相关途径扰动之间的潜在联系。