Unique patterns of lower respiratory tract microbiota are associated with inflammation and hospital mortality in acute respiratory distress syndrome
Unique patterns of lower respiratory tract microbiota are associated with inflammation and hospital mortality in acute respiratory distress syndrome
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DOI：
10.1186/s12931-019-1203-y
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发表时间：
2019-11-06
影响因子：
5.8
通讯作者：
Shime, Nobuaki
中科院分区：
文献类型：
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作者：
Kyo, Michihito;Nishioka, Keisuke;Shime, Nobuaki
背景肺微生物组维持肺内免疫系统的稳态。在急性呼吸窘迫综合征 (ARDS) 中，肺部微生物组富含肠道来源的细菌；然而，与 ARDS 患者发病率和死亡率相关的特定微生物组仍不清楚。这项研究调查了与 ARDS 患者死亡率相关的肺部微生物组的特定模式。方法 我们分析了 ARDS 患者和对照受试者的支气管肺泡灌洗液 (BALF) 的肺部微生物组。我们测量了 16S rRNA 以及血清和 BALF 细胞因子（白细胞介素 [IL]-6、IL-8、晚期糖基化终产物受体和血管生成素-2）的拷贝数。结果 我们分析了 47 名被诊断患有 ARDS（n = 40）或不患有 ARDS（n = 7；对照）的机械通气患者。与对照组相比，ARDS 患者的 α 多样性显着降低（6.24 vs. 8.07，P = 0.03）。与对照组相比，ARDS 组的 16S rRNA 基因拷贝数趋于增加（3.83 x 10(6) vs. 1.01 x 10(5) 拷贝/mL，P = 0.06）。 ARDS 患者被分为医院幸存者 (n = 24) 和非幸存者组 (n = 16)。非幸存者的血清 IL-6 水平显着高于幸存者（567 vs. 214 pg/mL，P = 0.027）。非幸存者中16S rRNA拷贝数与血清IL-6水平显着相关（r = 0.615，P < 0.05）。非幸存者中β变形菌的拷贝数和相对丰度显着低于幸存者（分别为713 vs. 7812，P = 0.012；1.22% vs. 0.08%，P = 0.02）。相反，非幸存者中葡萄球菌、链球菌和肠杆菌的拷贝数与血清IL-6水平显着相关（分别为r = 0.579，P < 0.05；r = 0.604，P < 0.05；r = 0.588，P < 0.05）。结论 ARDS患者肺部细菌负荷有增加趋势，α多样性显着降低。 β变形菌的减少和葡萄球菌、链球菌和肠杆菌科的增加可能代表了一种独特的微生物群落结构，与血清 IL-6 和医院死亡率的增加相关。
Background The lung microbiome maintains the homeostasis of the immune system within the lungs. In acute respiratory distress syndrome (ARDS), the lung microbiome is enriched with gut-derived bacteria; however, the specific microbiome associated with morbidity and mortality in patients with ARDS remains unclear. This study investigated the specific patterns of the lung microbiome that are correlated with mortality in ARDS patients. Methods We analyzed the lung microbiome from the bronchoalveolar lavage fluid (BALF) of patients with ARDS and control subjects. We measured the copy numbers of 16S rRNA and the serum and BALF cytokines (interleukin [IL]-6, IL-8, receptor for advanced glycation end products, and angiopoietin-2). Results We analyzed 47 mechanically ventilated patients diagnosed with (n = 40) or without (n = 7; control) ARDS. The alpha diversity was significantly decreased in ARDS patients compared with that of the controls (6.24 vs. 8.07, P = 0.03). The 16S rRNA gene copy numbers tended to be increased in the ARDS group compared with the controls (3.83 x 10(6) vs. 1.01 x 10(5) copies/mL, P = 0.06). ARDS patients were subdivided into the hospital survivor (n = 24) and non-survivor groups (n = 16). Serum IL-6 levels were significantly higher in the non-survivors than in the survivors (567 vs. 214 pg/mL, P = 0.027). The 16S rRNA copy number was significantly correlated with serum IL-6 levels in non-survivors (r = 0.615, P < 0.05). The copy numbers and relative abundance of betaproteobacteria were significantly lower in the non-survivors than in the survivors (713 vs. 7812, P = 0.012; 1.22% vs. 0.08%, P = 0.02, respectively). Conversely, the copy numbers of Staphylococcus, Streptococcus and Enterobacteriaceae were significantly correlated with serum IL-6 levels in the non-survivors (r = 0.579, P < 0.05; r = 0.604, P < 0.05; r = 0.588, P < 0.05, respectively). Conclusions The lung bacterial burden tended to be increased, and the alpha diversity was significantly decreased in ARDS patients. The decreased Betaproteobacteria and increased Staphylococcus, Streptococcus and Enterobacteriaceae might represent a unique microbial community structure correlated with increased serum IL-6 and hospital mortality.