Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
J Transl Med. 2021 Mar 23;19(1):121. doi: 10.1186/s12967-021-02788-4.
Chronic obstructive pulmonary disease (COPD) is a progressive, life-threatening lung disease with increasing prevalence and incidence worldwide. Increasing evidence suggests that lung microbiomes might play a physiological role in acute exacerbations of COPD. The objective of this study was to characterize the association of the microbiota and exacerbation risk or airflow limitation in stable COPD patients.
The sputum microbiota from 78 COPD outpatients during periods of clinical stability was investigated using 16S rRNA V3-V4 amplicon sequencing. The microbiome profiles were compared between patients with different risks of exacerbation, i.e., the low risk exacerbator (LRE) or high risk exacerbator (HRE) groups, and with different airflow limitation severity, i.e., mild to moderate (FEV1 ≥ 50; PFT I) or severe to very severe (FEV1 < 50; PFT II).
The bacterial diversity (Chao1 and observed OTUs) was significantly decreased in the HRE group compared to that in the LRE group. The top 3 dominant phyla in sputum were Firmicutes, Actinobacteria, and Proteobacteria, which were similar in the HRE and LRE groups. At the genus level, compared to that in the LRE group (41.24%), the proportion of Streptococcus was slightly decreased in the HRE group (28.68%) (p = 0.007). However, the bacterial diversity and the proportion of dominant bacteria at the phylum and genus levels were similar between the PFT I and PFT II groups. Furthermore, the relative abundances of Gemella morbillorum, Prevotella histicola, and Streptococcus gordonii were decreased in the HRE group compared to those in the LRE group according to linear discriminant analysis effect size (LEfSe). Microbiome network analysis suggested altered bacterial cooperative regulation in different exacerbation phenotypes. The proportions of Proteobacteria and Neisseria were negatively correlated with the FEV1/FVC value. According to functional prediction of sputum bacterial communities through Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis, genes involved in lipopolysaccharide biosynthesis and energy metabolism were enriched in the HRE group.
The present study revealed that the sputum microbiome changed in COPD patients with different risks of exacerbation. Additionally, the bacterial cooperative networks were altered in the HRE patients and may contribute to disease exacerbation. Our results provide evidence that sputum microbiome community dysbiosis is associated with different COPD phenotypes, and we hope that by understanding the lung microbiome, a potentially modifiable clinical factor, further targets for improved COPD therapies during the clinically stable state may be elucidated.
慢性阻塞性肺疾病（COPD）是一种具有全球发病率和患病率日益增加的进行性、危及生命的肺部疾病。越来越多的证据表明，肺部微生物组可能在 COPD 的急性加重中发挥生理作用。本研究的目的是描述稳定期 COPD 患者的微生物组与加重风险或气流受限的关联。
使用 16S rRNA V3-V4 扩增子测序，研究了 78 例 COPD 门诊患者在临床稳定期的痰微生物群。比较了不同加重风险（低风险加重者[LRE]或高风险加重者[HRE]）患者之间以及不同气流受限严重程度（FEV1≥50；PFT I）或严重至非常严重（FEV1<50；PFT II）患者之间的微生物组谱。
与 LRE 组相比，HRE 组的细菌多样性（Chao1 和观察到的 OTUs）明显降低。痰液中前 3 个优势菌门是厚壁菌门、放线菌门和变形菌门，在 HRE 和 LRE 组中相似。在属水平上，与 LRE 组（41.24%）相比，HRE 组链球菌的比例略有下降（28.68%）（p=0.007）。然而，PFT I 和 PFT II 组之间的细菌多样性和主要细菌的属水平比例相似。此外，根据线性判别分析效应大小（LEfSe），HRE 组中流感嗜血杆菌、龋齿放线菌和戈登链球菌的相对丰度降低。微生物组网络分析表明，不同加重表型的细菌协同调节发生改变。变形菌门和奈瑟菌的比例与 FEV1/FVC 值呈负相关。通过未观察状态重建的群落系统发育分析（PICRUSt）对痰细菌群落进行功能预测，发现 HRE 组中参与脂多糖生物合成和能量代谢的基因富集。
本研究表明，不同加重风险的 COPD 患者的痰微生物组发生了变化。此外，HRE 患者的细菌协同网络发生改变，可能导致疾病加重。我们的研究结果表明，痰微生物组群落失调与不同的 COPD 表型相关，我们希望通过了解肺部微生物组这一潜在可改变的临床因素，进一步阐明在临床稳定状态下改善 COPD 治疗的潜在靶点。
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