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.

中文翻译：

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慢性香烟烟雾暴露和肺炎球菌感染会导致小鼠口咽部微生物群失调，并导致长期肺部损伤


吸烟或肺部感染等环境因素可能会通过改变呼吸道微生物组来影响慢性阻塞性肺病 (COPD) 的进展。然而，疾病本身是否会引起或维持菌群失调仍不清楚。在这项纵向研究中，我们调查了小鼠（每笼 5-10 只小鼠）在长期接触香烟烟雾或接触室内空气 6 个月之前、期间和之后 3 个月内的口咽微生物群组成和疾病进展。香烟烟雾暴露引起的肺气肿可在暴露 6 个月结束时以及停止吸烟后 3 个月内测量。使用经典培养方法和 16S rRNA 测序，我们观察到香烟烟雾暴露改变了口咽部微生物群的相对组成并降低了其多样性（ P <0 id=143>P <0 id=144>肺炎链球菌对已确定的烟雾诱导与感染但未接触烟雾的对照组相比，还评估了接种肺炎链球菌引起的肺损伤和微生物群组成的改变时间更长（ P = 0.01）。烟雾和肺炎球菌感染导致微生物群改变和肺气肿发展，停止接触烟雾和感染清除后，微生物群组成紊乱发生逆转，但肺部损伤并未逆转，这表明肺部结构的变化不足以维持紊乱的微生物群。在小鼠中。 气道微生物群的变化是否有助于诱发肺气肿需要进一步研究。