Zhang Yao, Yan Jiaju, Ren Yuan, Li Lifang, You Xiaojie, Xie Yujia, Chen Weihong, Zhao Hui, Wang Dongming
Department of Pulmonary and Critical Care Medicine, The Second Hospital of Shanxi Medical University, NO.382 Wuyi Road,Xinghualing District, Taiyuan, 030001, Shanxi, P.R. China.
The Second Clinical Medical college, Shanxi Medical University, Taiyuan, China.
Sci Rep. 2025 Jul 2;15(1):22990. doi: 10.1038/s41598-025-06411-0.
The exact molecular mechanisms of coal workers' pneumoconiosis (CWP) are still unknown. The purpose of this study is to investigate how the lung microbiota may contribute to the development of CWP. The rats were divided into five groups, including the control group, CWP group, silicosis group, CWP + antibiotic group, and CWP + MCC950 group. An animal model of CWP and silicosis was established using a non-exposed tracheal instillation method. The CWP + antibiotic group was treated with drinking and nasal drip broad-spectrum antibiotics in CWP rats, while the CWP + MCC950 group received intraperitoneal injections of NLRP3 inhibitors MCC950 in CWP rats. 16S rRNA sequencing was used to detect the lung microbiota in rats. Real-time fluorescence quantitative PCR was performed to detect the expression of NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1, IL-1β, collagen I, and fibronectin. The lung microbiota of exposed to coal dust exhibits an increase in Firmicutes, Staphylococcus, and Streptococcus, and decreases in Bacteroidota, Rothia, Achromobacter, and Lactobacillus, and an increase in mRNA levels of fibrotic and inflammatory markers. Antibiotic intervention and MCC950 had consistent impacts on the predominant microbiota in the lungs and the changes are essentially in opposition to the trends found in the CWP and control groups, whereas mRNA levels of fibrotic and inflammatory markers reduced. The richness of some prominent bacterial communities changed as a result of coal dust exposure, which could be a contributing factor to the inflammation and fibrosis caused by coal dust. Lung microbiota may serve as a key pathogenic mechanism in CWP.
煤工尘肺(CWP)的确切分子机制仍不清楚。本研究的目的是探讨肺部微生物群如何促进CWP的发展。将大鼠分为五组,包括对照组、CWP组、矽肺组、CWP +抗生素组和CWP + MCC950组。采用非暴露气管内滴注法建立CWP和矽肺动物模型。CWP +抗生素组在CWP大鼠中通过饮水和滴鼻给予广谱抗生素治疗,而CWP + MCC950组在CWP大鼠中腹腔注射NLRP3抑制剂MCC950。采用16S rRNA测序检测大鼠肺部微生物群。进行实时荧光定量PCR检测NLRP3、凋亡相关斑点样蛋白(ASC)、半胱天冬酶-1、白细胞介素-1β、胶原蛋白I和纤连蛋白的表达。暴露于煤尘的大鼠肺部微生物群中厚壁菌门、葡萄球菌属和链球菌属增加,拟杆菌门、罗氏菌属、无色杆菌属和乳杆菌属减少,纤维化和炎症标志物的mRNA水平升高。抗生素干预和MCC950对肺部主要微生物群有一致的影响,且变化基本上与CWP组和对照组的趋势相反,而纤维化和炎症标志物的mRNA水平降低。煤尘暴露导致一些突出细菌群落的丰富度发生变化,这可能是煤尘引起炎症和纤维化的一个促成因素。肺部微生物群可能是CWP的关键致病机制。