Exposure to diesel exhaust particles results in altered lung microbial profiles, associated with increased reactive oxygen species/reactive nitrogen species and inflammation, in C57Bl/6 wildtype mice on a high-fat diet.
Exposure to diesel exhaust particles results in altered lung microbial profiles, associated with increased reactive oxygen species/reactive nitrogen species and inflammation, in C57Bl/6 wildtype mice on a high-fat diet.
复制标题
对于食用高脂饮食的C57Bl/6野生型小鼠，暴露于柴油机尾气颗粒会导致肺部微生物分布改变，同时活性氧/活性氮增加，并引发炎症。
DOI：
10.1186/s12989-020-00393-9
复制
发表时间：
2021-01-08
影响因子：
10
通讯作者：
Lund AK
中科院分区：
文献类型：
--
作者：
Daniel S;Phillippi D;Schneider LJ;Nguyen KN;Mirpuri J;Lund AK
接触交通产生的排放物与慢性阻塞性肺病 (COPD) 和特发性肺纤维化 (IPF) 等炎症性肺部疾病的发生和恶化有关。尽管许多肺部疾病显示变形菌的扩张，但交通产生的颗粒物污染物对肺部微生物群的作用尚未得到很好的表征。因此，我们研究了这样的假设：暴露于柴油机尾气颗粒（DEP）可以改变肺部共生微生物群，从而促进肺部免疫和炎症反应的改变。我们的目的是了解饮食是否也可能导致共生肺微生物组的改变，无论是单独的还是与暴露相关的。为此，我们使用常规饮食 (LF) 或高脂 (HF) 饮食（45% kcal 脂肪）的雄性 C57Bl/6 小鼠（4-6 周龄），随机分配通过口咽抽吸暴露于 35μg DEP，悬浮于 35μl 0.9% 无菌盐水或仅无菌盐水（对照）中，每周两次，持续 30 天。在整个研究过程中，另一组采用 HF 饮食的研究动物同时在饮用水中每天添加 0.3 克 Winclove Ecologic® Barrier 益生菌。我们的结果表明，DEP 暴露会增加肺肿瘤坏死因子 (TNF)-α、白细胞介素 (IL)-10、Toll 样受体 (TLR)-2、TLR-4 和核因子 kappa B (NF-κB) 的组织学和 RT-qPCR，以及支气管肺泡灌洗液 (BALF) 中的免疫球蛋白 A (IgA) 和免疫球蛋白 G (IgG)，如通过 ELISA 定量。我们还观察到，DEP 暴露和 HF 饮食动物的肺部巨噬细胞浸润和过氧亚硝酸盐（活性氧 (ROS) + 活性氮 (RNS) 的标记物）、免疫荧光染色有所增加，同时 DEP 暴露和 HF 饮食消耗进一步加剧了这种情况。组织学检查显示，无论饮食如何，暴露于 DEP 的小鼠肺部炎症和胶原蛋白沉积均增强。我们通过细菌 16S rRNA 的 qPCR 观察到，在接受 HF 饮食的 DEP 暴露小鼠的 BALF 中，变形菌出现了扩增，而益生菌治疗则减少了这种情况。我们的研究结果表明，接触 DEP 会以 ROS-RNS 介导的方式引起持续的炎症和细菌改变，而同时食用 HF 饮食会加剧这种情况。在线版本包含可在 10.1186/s12989-020-00393-9 获取的补充材料。
Exposure to traffic-generated emissions is associated with the development and exacerbation of inflammatory lung disorders such as chronic obstructive pulmonary disorder (COPD) and idiopathic pulmonary fibrosis (IPF). Although many lung diseases show an expansion of Proteobacteria, the role of traffic-generated particulate matter pollutants on the lung microbiota has not been well-characterized. Thus, we investigated the hypothesis that exposure to diesel exhaust particles (DEP) can alter commensal lung microbiota, thereby promoting alterations in the lung’s immune and inflammatory responses. We aimed to understand whether diet might also contribute to the alteration of the commensal lung microbiome, either alone or related to exposure. To do this, we used male C57Bl/6 mice (4–6-week-old) on either regular chow (LF) or high-fat (HF) diet (45% kcal fat), randomly assigned to be exposed via oropharyngeal aspiration to 35 μg DEP, suspended in 35 μl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. A separate group of study animals on the HF diet was concurrently treated with 0.3 g/day of Winclove Ecologic® Barrier probiotics in their drinking water throughout the study. Our results show that DEP-exposure increases lung tumor necrosis factor (TNF)-α, interleukin (IL)-10, Toll-like receptor (TLR)-2, TLR-4, and the nuclear factor kappa B (NF-κB) histologically and by RT-qPCR, as well as Immunoglobulin A (IgA) and Immunoglobulin G (IgG) in the bronchoalveolar lavage fluid (BALF), as quantified by ELISA. We also observed an increase in macrophage infiltration and peroxynitrite, a marker of reactive oxygen species (ROS) + reactive nitrogen species (RNS), immunofluorescence staining in the lungs of DEP-exposed and HF-diet animals, which was further exacerbated by concurrent DEP-exposure and HF-diet consumption. Histological examinations revealed enhanced inflammation and collagen deposition in the lungs DEP-exposed mice, regardless of diet. We observed an expansion of Proteobacteria, by qPCR of bacterial 16S rRNA, in the BALF of DEP-exposed mice on the HF diet, which was diminished with probiotic-treatment. Our findings suggest that exposure to DEP causes persistent and sustained inflammation and bacterial alterations in a ROS-RNS mediated fashion, which is exacerbated by concurrent consumption of an HF diet. The online version contains supplementary material available at 10.1186/s12989-020-00393-9.
登录
查看更多内容
影响因子：
168.9
作者：
Dickson, Robert P.;Martinez, Fernando J.;Huffnagle, Gary B.
通讯作者：
Huffnagle, Gary B.
DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
DOI：
10.1080/20010001.2019.1647400
发表时间：
2019-07-26
期刊：
PATHOBIOLOGY OF AGING AND AGE-RELATED DISEASES
影响因子：
--
作者：
Bjorner, Marianne;Zhu, Lida
通讯作者：
Zhu, Lida
影响因子：
168.9
作者：
Guarnieri, Michael;Balmes, John R.
通讯作者：
Balmes, John R.
影响因子：
6.7
作者：
Flynn, Jeffrey M.;Niccum, David;Hunter, Ryan C.
通讯作者：
Hunter, Ryan C.