Yadav Brijesh, Bhattacharya Sukanta S, Rosen Lauren, Nagpal Ravinder, Yadav Hariom, Yadav Jagjit S
Pulmonary Pathogenesis and Immunotoxicology Laboratory, Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056, USA.
Department of Pathology and Laboratory Medicine, University of Cincinnati, UC Health University Hospital Laboratory Medicine Building, Suite 110234 Goodman Street, Cincinnati, OH 45219-0533, USA.
Nanomaterials (Basel). 2024 Feb 4;14(3):314. doi: 10.3390/nano14030314.
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.
口腔呼吸道微生物群会受到吸烟等可吸入暴露的影响，并与呼吸道健康状况相关。然而，对于新兴毒物，尤其是工程纳米颗粒单独或与吸烟共同暴露的影响，人们了解甚少。在此，我们研究了亚慢性暴露于碳纳米管（CNT）颗粒、香烟烟雾提取物（CSE）及其组合的影响。使用基于16S rRNA的宏基因组学对口腔、鼻腔和肺部微生物群进行了表征。这些暴露导致肺部微生物群发生了以下变化：CNT导致微生物群从变形菌门和拟杆菌门转变为厚壁菌门和柔膜菌门；CSE导致微生物群从变形菌门转变为拟杆菌门；与对照组相比，共同暴露（CNT+CSE）产生了混合效应，拟杆菌门（由于CNT的作用）和柔膜菌门（由于CSE的作用）的数量维持在较高水平。口腔微生物群分析显示以下菌属数量丰富：不动杆菌属（CNT）、葡萄球菌属、聚集杆菌属、全杆菌属和链球菌属（CSE），以及碱杆菌属（CNT+CSE）。这些促炎微生物群的变化与肺黏膜稳态/防御蛋白，即水通道蛋白1（AQP-1）、表面活性蛋白A（SP-A）、粘蛋白5b（MUC5B）和IgA相对表达的变化相关。微生物群的耗竭在不同程度上逆转了这些扰动，证实了口腔呼吸道生态失调在肺黏膜毒性中的调节作用。这是首次证明特定的口腔呼吸道微生物群成分是暴露肺部中毒物作用的潜在调节因子。
