Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Department of Infectious Diseases, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
Respir Res. 2019 Nov 6;20(1):246. doi: 10.1186/s12931-019-1203-y.
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.
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).
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 × 10 vs. 1.01 × 10 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).
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.
The institutional review boards of Hiroshima University (Trial registration: E-447-4, registered 16 October 2019) and Kyoto Prefectural University of Medicine (Trial registration: ERB-C-973, registered 19 October 2017) approved an opt-out method of informed consent.
肺部微生物组维持着肺部免疫系统的内稳态。在急性呼吸窘迫综合征（ARDS）中，肺部微生物组中富含来自肠道的细菌；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。本研究调查了与 ARDS 患者死亡率相关的肺部微生物组的特定模式。
我们分析了 ARDS 患者和对照者支气管肺泡灌洗液（BALF）中的肺部微生物组。我们测量了 16S rRNA 的拷贝数以及血清和 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）。
我们分析了 47 名接受机械通气的患者，其中 40 名诊断为 ARDS（n=40），7 名未诊断为 ARDS（n=7；对照组）。与对照组相比，ARDS 患者的 alpha 多样性显著降低（6.24 与 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（3.83×10 与 1.01×10 拷贝/mL，P=0.06）。ARDS 患者分为住院幸存者（n=24）和非幸存者（n=16）组。非幸存者的血清 IL-6 水平明显高于幸存者（567 与 214 pg/mL，P=0.027）。非幸存者的 16S rRNA 拷贝数与血清 IL-6 水平显著相关（r=0.615，P<0.05）。与幸存者相比，非幸存者的 betaproteobacteria 拷贝数和相对丰度显著降低（713 与 7812，P=0.012；1.22%与 0.08%，P=0.02，分别）。相反，非幸存者的金黄色葡萄球菌、链球菌和肠杆菌科的拷贝数与血清 IL-6 水平显著相关（r=0.579，P<0.05；r=0.604，P<0.05；r=0.588，P<0.05，分别）。
ARDS 患者肺部细菌负荷趋于增加，alpha 多样性显著降低。减少的 Betaproteobacteria 和增加的金黄色葡萄球菌、链球菌和肠杆菌科可能代表与血清 IL-6 增加和住院死亡率相关的独特微生物群落结构。
广岛大学的机构审查委员会（试验注册：E-447-4，2019 年 10 月 16 日注册）和京都府立医科大学的机构审查委员会（试验注册：ERB-C-973，2017 年 10 月 19 日注册）批准了一种选择退出的知情同意方法。
