Pyrosequencing Unveils Cystic Fibrosis Lung Microbiome Differences Associated with a Severe Lung Function Decline

Chronic airway infection is a hallmark feature of cystic fibrosis (CF) disease. In the present study, sputum samples from CF patients were collected and characterized by 16S rRNA gene-targeted approach, to assess how lung microbiota composition changes following a severe decline in lung function. In particular, we compared the airway microbiota of two groups of patients with CF, i.e. patients with a substantial decline in their lung function (SD) and patients with a stable lung function (S). The two groups showed a different bacterial composition, with SD patients reporting a more heterogeneous community than the S ones. Pseudomonas was the dominant genus in both S and SD patients followed by Staphylococcus and Prevotella. Other than the classical CF pathogens and the most commonly identified non-classical genera in CF, we found the presence of the unusual anaerobic genus Sneathia. Moreover, the oligotyping analysis revealed the presence of other minor genera described in CF, highlighting the polymicrobial nature of CF infection. Finally, the analysis of correlation and anti-correlation networks showed the presence of antagonism and ecological independence between members of Pseudomonas genus and the rest of CF airways microbiota, with S patients showing a more interconnected community in S patients than in SD ones. This population structure suggests a higher resilience of S microbiota with respect to SD, which in turn may hinder the potential adverse impact of aggressive pathogens (e.g. Pseudomonas). In conclusion, our findings shed a new light on CF airway microbiota ecology, improving current knowledge about its composition and polymicrobial interactions in patients with CF.

慢性气道感染是囊性纤维化（CF）的标志性病理特征。本研究收集了CF患者的痰液样本，采用16S rRNA基因靶向测序技术对样本进行表征，旨在探究肺功能严重下降时肺部微生物群组成的变化规律。具体而言，本研究将CF患者分为两组以比较其气道微生物群：即肺功能大幅下降组（SD）与肺功能稳定组（S）。结果显示，两组患者的细菌组成存在显著差异，SD组的微生物群落异质性高于S组。假单胞菌属（Pseudomonas）为两组患者的优势菌属，其次为葡萄球菌属（Staphylococcus）与普雷沃菌属（Prevotella）。除经典CF致病菌及CF中最常检出的非经典菌属外，本研究还检出了罕见厌氧菌属斯涅氏菌属（Sneathia）。此外，寡分型分析还揭示了CF中其他少见菌属的存在，进一步凸显了CF感染的多微生物特性。最后，相关与负相关网络分析显示，假单胞菌属成员与CF气道其余微生物群之间存在拮抗作用与生态独立性；且S组的微生物群落互联程度高于SD组。这种种群结构表明，S组微生物群的恢复力优于SD组，这或可削弱致病性强的致病菌（如假单胞菌）所带来的潜在不良影响。综上，本研究结果为CF气道微生物群生态学提供了新的视角，深化了当前对CF患者肺部微生物群组成及其多微生物相互作用的认知。