PDF(Sci-hub)
Abstract：
BACKGROUND: Recent studies have revealed that the lung microbiota of critically ill patients is altered and predicts clinical outcomes. The incidence of invasive fungal infections, namely, invasive pulmonary aspergillosis (IPA), in immunocompromised patients is increasing, but the clinical significance of variations in lung bacterial communities is unknown.
OBJECTIVE: To define the contribution of the lung microbiota to the development and course of IPA.
METHODS: We performed an observational cohort study to characterise the lung microbiota in 104 immunocompromised patients using bacterial 16S ribosomal RNA gene sequencing on bronchoalveolar lavage samples sampled on clinical suspicion of infection. Associations between lung dysbiosis in IPA and pulmonary immunity were evaluated by quantifying alveolar cytokines and chemokines and immune cells. The contribution of microbial signatures to patient outcome was assessed by estimating overall survival.
RESULTS: Patients diagnosed with IPA displayed a decreased alpha diversity, driven by a markedly increased abundance of the Staphylococcus, Escherichia, Paraclostridium and Finegoldia genera and a decreased proportion of the Prevotella and Veillonella genera. The overall composition of the lung microbiome was influenced by the neutrophil counts and associated with differential levels of alveolar cytokines. Importantly, the degree of bacterial diversity at the onset of IPA predicted the survival of infected patients.
CONCLUSIONS: Our results reveal the lung microbiota as an understudied source of clinical variation in patients at risk of IPA and highlight its potential as a diagnostic and therapeutic target in the context of respiratory fungal diseases.
OBJECTIVE: To define the contribution of the lung microbiota to the development and course of IPA.
METHODS: We performed an observational cohort study to characterise the lung microbiota in 104 immunocompromised patients using bacterial 16S ribosomal RNA gene sequencing on bronchoalveolar lavage samples sampled on clinical suspicion of infection. Associations between lung dysbiosis in IPA and pulmonary immunity were evaluated by quantifying alveolar cytokines and chemokines and immune cells. The contribution of microbial signatures to patient outcome was assessed by estimating overall survival.
RESULTS: Patients diagnosed with IPA displayed a decreased alpha diversity, driven by a markedly increased abundance of the Staphylococcus, Escherichia, Paraclostridium and Finegoldia genera and a decreased proportion of the Prevotella and Veillonella genera. The overall composition of the lung microbiome was influenced by the neutrophil counts and associated with differential levels of alveolar cytokines. Importantly, the degree of bacterial diversity at the onset of IPA predicted the survival of infected patients.
CONCLUSIONS: Our results reveal the lung microbiota as an understudied source of clinical variation in patients at risk of IPA and highlight its potential as a diagnostic and therapeutic target in the context of respiratory fungal diseases.
摘要：
背景：最近的研究表明，危重患者的肺部微生物群发生了改变，并可预测临床结果。侵袭性真菌感染的发生率，即,侵袭性肺曲霉病(IPA),免疫功能低下的患者正在增加，但肺部细菌群落变化的临床意义尚不清楚。
目的：明确肺部菌群对IPA发生发展和进程的影响。
方法：我们进行了一项观察性队列研究，使用细菌16S核糖体RNA基因测序对临床怀疑感染的支气管肺泡灌洗液样本进行了104例免疫功能低下患者的肺部菌群特征研究。通过量化肺泡细胞因子，趋化因子和免疫细胞来评估IPA中肺菌群失调与肺免疫之间的关联。通过估计总生存期来评估微生物特征对患者预后的贡献。
结果：诊断为IPA的患者显示α多样性下降，受葡萄球菌丰度显著增加的驱动，埃希氏菌,梭状芽胞杆菌属和Finegoldia属，普雷沃氏菌属和韦洛氏菌属的比例降低。肺微生物组的总体组成受嗜中性粒细胞计数的影响，并与肺泡细胞因子的不同水平有关。重要的是,IPA发病时的细菌多样性程度预测了感染患者的生存。
结论：我们的研究结果表明，肺部微生物群是存在IPA风险的患者临床变异的一个研究不足的来源，并强调了其作为呼吸道真菌病诊断和治疗靶点的潜力。
目的：明确肺部菌群对IPA发生发展和进程的影响。
方法：我们进行了一项观察性队列研究，使用细菌16S核糖体RNA基因测序对临床怀疑感染的支气管肺泡灌洗液样本进行了104例免疫功能低下患者的肺部菌群特征研究。通过量化肺泡细胞因子，趋化因子和免疫细胞来评估IPA中肺菌群失调与肺免疫之间的关联。通过估计总生存期来评估微生物特征对患者预后的贡献。
结果：诊断为IPA的患者显示α多样性下降，受葡萄球菌丰度显著增加的驱动，埃希氏菌,梭状芽胞杆菌属和Finegoldia属，普雷沃氏菌属和韦洛氏菌属的比例降低。肺微生物组的总体组成受嗜中性粒细胞计数的影响，并与肺泡细胞因子的不同水平有关。重要的是,IPA发病时的细菌多样性程度预测了感染患者的生存。
结论：我们的研究结果表明，肺部微生物群是存在IPA风险的患者临床变异的一个研究不足的来源，并强调了其作为呼吸道真菌病诊断和治疗靶点的潜力。
