PDF(Pubmed)
Abstract：
The oro-respiratory microbiome is impacted by inhalable exposures such as smoking and has been associated with respiratory health conditions. However, the effect of emerging toxicants, particularly engineered nanoparticles, alone or in co-exposure with smoking, is poorly understood. Here, we investigated the impact of sub-chronic exposure to carbon nanotube (CNT) particles, cigarette smoke extract (CSE), and their combination. The oral, nasal, and lung microbiomes were characterized using 16S rRNA-based metagenomics. The exposures caused the following shifts in lung microbiota: CNT led to a change from Proteobacteria and Bacteroidetes to Firmicutes and Tenericutes; CSE caused a shift from Proteobacteria to Bacteroidetes; and co-exposure (CNT+CSE) had a mixed effect, maintaining higher numbers of Bacteroidetes (due to the CNT effect) and Tenericutes (due to the CSE effect) compared to the control group. Oral microbiome analysis revealed an abundance of the following genera: Acinetobacter (CNT), Staphylococcus, Aggregatibacter, Allobaculum, and Streptococcus (CSE), and Alkalibacterium (CNT+CSE). These proinflammatory microbial shifts correlated with changes in the relative expression of lung mucosal homeostasis/defense proteins, viz., aquaporin 1 (AQP-1), surfactant protein A (SP-A), mucin 5b (MUC5B), and IgA. Microbiota depletion reversed these perturbations, albeit to a varying extent, confirming the modulatory role of oro-respiratory dysbiosis in lung mucosal toxicity. This is the first demonstration of specific oro-respiratory microbiome constituents as potential modifiers of toxicant effects in exposed lungs.
摘要：
口腔呼吸微生物组受吸烟等可吸入暴露的影响，并与呼吸健康状况相关。然而,新出现的有毒物质的影响，特别是工程纳米粒子，单独或与吸烟共同接触，知之甚少。这里,我们调查了亚慢性暴露于碳纳米管（CNT）颗粒的影响，香烟烟雾提取物（CSE），和他们的组合。口头，鼻部,和肺微生物组使用基于16SrRNA的宏基因组学进行表征。暴露导致肺部微生物群发生以下变化：CNT导致从变形杆菌和拟杆菌转变为Firmicutes和Tenericutes；CSE导致从变形杆菌转变为拟杆菌；共同暴露（CNTCSE）具有混合作用，与对照组相比,保持较高数量的拟杆菌(由于CNT效应)和拟杆菌(由于CSE效应)。口腔微生物组分析揭示了丰富的以下属：不动杆菌（CNT），葡萄球菌,Aggregatibacter,Allobaculum,和链球菌（CSE），和碱性细菌(CNT+CSE)。这些促炎微生物转移与肺粘膜稳态/防御蛋白的相对表达变化相关，viz.,水通道蛋白1（AQP-1），表面活性剂蛋白A（SP-A），粘蛋白5b（MUC5B），还有IgA.微生物群的耗尽逆转了这些扰动，尽管在不同程度上，确认口呼吸菌群失调在肺粘膜毒性中的调节作用。这是特定的口呼吸微生物组成分作为暴露肺中毒性作用的潜在调节剂的首次证明。
