Respiratory Tract Dysbiosis Is Associated with Worse Outcomes in Mechanically Ventilated Patients
Respiratory Tract Dysbiosis Is Associated with Worse Outcomes in Mechanically Ventilated Patients
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DOI：
10.1164/rccm.201912-2441oc
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发表时间：
2020-12-15
影响因子：
24.7
通讯作者：
McVerry, Bryan J.
中科院分区：
文献类型：
--
作者：
Kitsios, Georgios D.;Yang, Haopu;McVerry, Bryan J.
理由：宿主炎症反应与危重患者的不良结局密切相关，但这种异质反应的生物学基础尚未明确。目的：我们研究了呼吸道微生物组特征是否与宿主炎症和急性呼吸衰竭的临床结果相关。方法：我们收集了机械通气患者的口腔拭子、气管内抽吸物 (ETA) 和血浆样本。我们进行了 16S 核糖体 RNA 基因测序来表征上呼吸道和下呼吸道微生物群，并根据临床变量以及先天免疫和炎症的血浆生物标志物将患者分为宿主反应亚表型。我们使用狄利克雷多项模型得出多样性指标和组成簇，并检查我们的数据与亚表型和临床结果的关联。测量和主要结果：来自 301 名机械通气受试者的口腔和 ETA 微生物群落在 a 和 ss 多样性方面具有显着的异质性。狄利克雷多项模型显示，与典型口腔微生物群多样性和相对丰度较高的患者相比，35% 的 ETA 样本中病原体多样性和富集度较低（例如，葡萄球菌或假单胞菌科相对丰度较高），与高炎症亚表型、较差的 30 天生存率和机械通气恢复时间较长（调整后的 P < 0.05）相关。口腔和 ETA 样本中存在菌群失调证据（“保护性”口腔来源共生菌的多样性和相对丰度较低）的患者（17%，合并菌群失调）的 30 天生存率显着低于无菌群失调的患者（55%；调整后的 P < 0.05）。临床结果。
Rationale: Host inflammatory responses have been strongly associated with adverse outcomes in critically ill patients, but the biologic underpinnings of such heterogeneous responses have not been defined.Objectives: We examined whether respiratory tract microbiome profiles are associated with host inflammation and clinical outcomes of acute respiratory failure.Methods: We collected oral swabs, endotracheal aspirates (ETAs), and plasma samples from mechanically ventilated patients. We performed 16S ribosomal RNA gene sequencing to characterize upper and lower respiratory tract microbiota and classified patients into host-response subphenotypes on the basis of clinical variables and plasma biomarkers of innate immunity and inflammation. We derived diversity metrics and composition clusters with Dirichlet multinomial models and examined our data for associations with subphenotypes and clinical outcomes.Measurements and Main Results: Oral and ETA microbial communities from 301 mechanically ventilated subjects had substantial heterogeneity in a and ss diversity. Dirichlet multinomial models revealed a cluster with low a diversity and enrichment for pathogens (e.g., high Staphylococcus or Pseudomonadaceae relative abundance) in 35% of ETA samples, associated with a hyperinflammatory subphenotype, worse 30-day survival, and longer time to liberation from mechanical ventilation (adjusted P < 0.05), compared with patients with higher a diversity and relative abundance of typical oral microbiota. Patients with evidence of dysbiosis (low a diversity and low relative abundance of "protective" oral-origin commensal bacteria) in both oral and ETA samples (17%, combined dysbiosis) had significantly worse 30-day survival and longer time to liberation from mechanical ventilation than patients without dysbiosis (55%; adjusted P < 0.05).Conclusions: Respiratory tract dysbiosis may represent an important, modifiable contributor to patient-level heterogeneity in systemic inflammatory responses and clinical outcomes.