Chronic cigarette smoke exposure and pneumococcal infection induce oropharyngeal microbiota dysbiosis and contribute to long-lasting lung damage in mice

Abstract

Environmental factors, such as cigarette smoking or lung infections, may influence chronic obstructive pulmonary disease (COPD) progression by modifying the respiratory tract microbiome. However, whether the disease itself induces or maintains dysbiosis remains undefined. In this longitudinal study, we investigated the oropharyngeal microbiota composition and disease progression of mice (in cages of 5–10 mice per cage) before, during and up to 3 months after chronic cigarette smoke exposure or exposure to room air for 6 months. Cigarette smoke exposure induced pulmonary emphysema measurable at the end of exposure for 6 months, as well as 3 months following smoke exposure cessation. Using both classical culture methods and 16S rRNA sequencing, we observed that cigarette smoke exposure altered the relative composition of the oropharyngeal microbiota and reduced its diversity (P <0.001). More than 60 taxa were substantially reduced after 6 months of smoke exposure (P <0.001) However, oropharyngeal microbiota disordering was reversed 3 months after smoke exposure cessation and no significant difference was observed compared to age-matched control mice. The effects of lung infection with Streptococcus pneumoniae on established smoke-induced emphysema and on the oropharyngeal microbiota were also evaluated. Inoculation with S. pneumoniae induced lung damage and altered the microbiota composition for a longer time compared to control groups infected but not previously exposed to smoke (P=0.01). Our data demonstrate effects of cigarette smoke and pneumococcus infection leading to altered microbiota and emphysema development. The reversal of the disordering of the microbiota composition, but not lung damage, following smoke exposure cessation and after clearance of infection suggest that changes in lung structure are not sufficient to sustain a disordered microbiota in mice. Whether changes in the airway microbiota contribute to inducing emphysema requires further investigation.

Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice

“…IAV causes subtle, transient changes in the microbial composition of the lower respiratory tract of mice, with Lactobacillus dominating ( Yildiz et al, 2018 ). Mice infected with S. pneumoniae after 6 months of exposure to cigarette smoke had decreased pulmonary microbiota diversity and increased Lactobacillaceae levels in the upper respiratory tract ( Hilty et al, 2020 ). However, it remains unclear how changes in the composition of lung microbiome in COPD mice with NTHi infection or IAV-NTHi coinfection.…”

Analysis of sputum microbial diversity in patients with different histological types of lung cancer

“…Previous studies had con rmed that the oral bacterial microbiome diversity and bacterial species of mice exposed to cigarette smoke was signi cantly lower than that of the control group. And the oral microbiome diversity of mice gradually recovered after the cigarette smoke exposure was stopped for 3 months [45] . Similar to previous researches, our results showed there was a signi cant difference in the respiratory bacterial microbiome between smokers and non-smokers (Fig.…”

Smoking-induced microbial dysbiosis in health and disease

“…Some of these limitations were resolved by Wang et al [ 87 ] who found in a larger cohort that the bacterial genera Moraxella and Haemophilus were significantly enriched in ex-smokers with COPD and associated with augmented inflammation [ 87 ], in agreement with other studies correlating Haemophilus with COPD severity [ 81 ]. Interestingly, a study in mice [ 88 ] found that exposure of mice to smoke for 6 months followed by 3 months of cessation caused irreversible emphysema, accompanied by a lower diversity and dysbiosis of the oropharyngeal microbiome, which was reverted following smoking cessation. In the mice previously exposed to smoke, pneumococcal infection led to increased chronic lung injury along with short-term alterations in the oropharyngeal microbiome [ 88 ].…”

“…Interestingly, a study in mice [ 88 ] found that exposure of mice to smoke for 6 months followed by 3 months of cessation caused irreversible emphysema, accompanied by a lower diversity and dysbiosis of the oropharyngeal microbiome, which was reverted following smoking cessation. In the mice previously exposed to smoke, pneumococcal infection led to increased chronic lung injury along with short-term alterations in the oropharyngeal microbiome [ 88 ]. Collectively, these studies present a distinct microbiome composition induced by smoking and COPD ( Figure 2 ).…”