The lethal chronic airway infection of the cystic fibrosis (CF) patients is predisposed by colonization of specific CF-philic pathogens or the CF microbiomes, but key processes and reasons of the microbiome settlement in the patients are yet to be fully understood, especially their survival and metabolic dynamics from normal to diseased status under treatment. Here, we report our meta-analysis results on CF airway microbiomes based on metabolic networks reconstructed from genome information at species level. The microbiomes of CF patients appear to engage much more redox-related activities than those of controls, and by constructing a large dataset of anti-oxidative stress (anti-OS) genes, our quantitative evaluation of the anti-OS capacity of each bacterial species in the CF microbiomes confirms strong conservation of the anti-OS responses within genera and also shows that the CF pathogens have significantly higher anti-OS capacity than commensals and other typical respiratory pathogens. In addition, the anti-OS capacity of a relevant species correlates with its relative fitness for the airways of CF patients over that for the airways of controls. Moreover, the total anti-OS capacity of the respiratory microbiome of CF patients is collectively higher than that of controls, which increases with disease progression, especially after episodes of acute exacerbation and antibiotic treatment. According to these results, we propose that the increased OS in the airways of CF patients may play an important role in reshaping airway microbiomes to a more resistant status that favors the pre-infection colonization of the CF pathogens for a higher anti-OS capacity.
囊性纤维化（cystic fibrosis，CF）是一种致命的遗传性疾病，在呼吸系统表现为特定的CF病原体的定植和慢性感染，以及进行性的氧化损伤和肺功能丧失。目前CF呼吸道微生物组研究发现，CF患者呼吸道病原体集中在铜绿假单胞菌、洋葱伯克霍尔德菌群等特定病原体，但CF患者微生物群和病原体定植的关键过程和原因还不清楚。针对这一问题，我们通过对CF患者和健康人肺部微生物组进行荟萃分析，来研究两者之间微生物群物代谢网络的变化，我们发现CF患者呼吸道微生物群比对照组具有更多的氧化还原相关基因。为此，我们通过文献调研，构建了抗氧化应激基因数据集，并定量评估了各个物种的抗氧化应激能力。 通过比较分析，我们发现CF相关病原体的抗氧化应激能力明显高于共生菌和其他常见的呼吸道病原体。此外，相关物种的抗氧化应激能力与其在CF患者呼吸道中的适应性具有密切关联，而且CF患者呼吸道微生物组的总体抗氧化应激能力高于健康对照，并随着疾病的发展而升高，特别是在急性发作和抗生素治疗后具有明显增加。根据这些结果，我们认为CF患者呼吸道中不断升高的氧化应激导致微生物组不断向更高的抗氧化应激能力菌群靠近，有利于CF病原体在感染前的定殖，在微生物组重塑中发挥了重要作用。





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