The Influence of Cigarette Smoke on Human and Murine Lung Microbiota

Microbes are predominant inhabitants in the world and are in direct contact with our various body surfaces including skin, gut, genitals and respiratory tract. Host and microbes are interconnected and they both affect and depend on each other. However, this close connection can be disturbed by diverse external factors. Imbalance in microbial composition has already been associated with chronic inflammatory diseases, mostly of gut and skin, but recently these associations have been made regarding chronic lung diseases (CLD) as well. Hence, an increased interest in lung microbiome research has emerged in the last decade. It is known that smoking is one of the major risk factors for the development of CLDs, however its impact on microbial composition is still poorly understood. Therefore, the present work aimed to delineate effects of cigarette smoke (CS) exposure on the respiratory microbiota and its capacity to recover after smoking cessation. To examine the role of CS on the microbiota of the upper (URT) and the lower respiratory tract (LRT), bronchoscopy was performed in healthy smokers, ex-smokers and never-smokers. Additionally, to get insights into early effects of smoking on the immune system and the microbial compositions of the lung and gut, mice were exposed to mainstream CS for four different treatment periods (7, 21, 37 or 56 days). Results from the human study confirmed strong overlap of the oropharyngeal and the lung microbiota, but this dynamic relationship was disturbed by smoking. CS had an impact on the relative abundances of certain potentially pathogenic bacterial taxa in different areas of the respiratory system. Certain taxa were detected exclusively in the lungs and correlated positively with all smoking related parameters. In the mouse experiment, the most important changes upon CS exposure were loss of body weight, an increase of neutrophils and lymphocytes at later timepoints, and KC/GRO and VEGF inflammatory mediators in the bronchoalveolar lavage fluid. Also, an overexpression of Cyp1A1 and MMP12 genes and overproduction of MMP12 protein was detected in the lung tissue. Bacterial communities were dominated in all groups by Firmicutes and Bacteroidetes in the gut and by Firmicutes, Actinobacteria, Proteobacteria and Bacteroidetes in the lungs. However, only the gut microbiota changed significantly upon CS exposure, with lower relative abundance of Prevotella and higher relative abundance of Clostridium and Mucispirillum. In conclusion, CS showed different effects on the microbial composition in the URT and the LRT, leading to a higher relative abundance of potential pathogens. Further, the mouse data indicated that longer exposure to mainstream CS induces a loss of body weight and an increases number of inflammatory cells with modulations of bacterial communities in the gut and lungs. However, the effect was more prominent in the gut than in the lungs. Of note, the obtained data regarding microbial composition are descriptive and thus limited to draw more detailed conclusions about functional meaning of observed changes.

Rights

Use and reproduction:

No license. The provisions of the German Copyright Act (UrhG) apply.

Please note that individual components of the publication may be subject to other licensing or copyright conditions.

Cite

Citation style:
Could not load citation form.