Data Sheet 4_Tripartite exacerbation stratification in AECOPD suggests a gradient of lower airway dysbiosis: a metagenomic transition from commensal taxa to pseudomonadota dominance.xlsx

BackgroundThe frequency of acute exacerbations (AECOPD) is a critical predictor of disease progression in chronic obstructive pulmonary disease (COPD). However, the dynamics of the lower respiratory microbiome across a spectrum of exacerbation frequency remain poorly characterized, limiting insights into microbial drivers of susceptibility.
MethodsWe conducted a cross-sectional study of 39 hospitalized AECOPD patients, stratified into non-frequent (NFE, ≤ 1 event/year, n = 11), moderate (ME, 2 events/year, n = 13), and frequent exacerbators (FE, ≥3 events/year, n = 15). Metagenomic next-generation sequencing (mNGS) was performed on bronchoalveolar lavage fluid (BALF) to profile the airway microbiome.
ResultsMicrobial alpha diversity exhibited a significant, graded decline from NFE to FE groups (e.g., Shannon index: NFE 3.68 ± 0.34, ME 3.02 ± 1.02, FE 0.84 ± 0.54; p < 0.05). Beta diversity analysis revealed distinct community clustering by exacerbation phenotype (PERMANOVA R2 = 0.19, p = 0.001). The FE group was characterized by a striking dominance of Pseudomonadota (relative abundance: 72.25%), which correlated positively with exacerbation frequency (r = 0.536, p < 0.001). In contrast, commensal taxa including Streptococcus (r = −0.814, p < 0.0001) and others within the Bacillota and Bacteroidota phyla were depleted in FE and were negatively associated with exacerbation frequency. Twelve exacerbation-resilient taxa (83.3% belonging to Bacillota/Bacteroidota) were positively correlated with FEV1% predicted (r = 0.322–0.483, p < 0.05). Alpha diversity indices showed a strong inverse association with exacerbation frequency (r = −0.84 to −0.86, p < 0.001) but not spirometric measures.
ConclusionOur findings delineate a gradient of airway microbial dysbiosis along the exacerbation frequency spectrum in COPD. The exacerbation-prone phenotype is defined by a loss of microbial diversity, expansion of Pseudomonadota, and depletion of potentially protective commensals. These microbiome features represent promising biomarkers for identifying high-risk patients and may inform future microbiome-targeted therapeutic strategies.

背景：慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）患者的急性加重频率是预测疾病进展的关键指标。然而，不同急性加重频率谱系下的下呼吸道微生物组动态变化特征仍未得到充分阐明，这限制了我们对宿主易感性微生物驱动因素的深入理解。
方法：本研究纳入39例住院的慢性阻塞性肺疾病急性加重（acute exacerbations of chronic obstructive pulmonary disease, AECOPD）患者，按急性加重频率分为非频繁加重组（non-frequent exacerbators, NFE：每年≤1次，n=11）、中等加重组（moderate exacerbators, ME：每年2次，n=13）及频繁加重组（frequent exacerbators, FE：每年≥3次，n=15）。对支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）进行宏基因组下一代测序（metagenomic next-generation sequencing, mNGS），以分析气道微生物组构成。
结果：气道微生物的α多样性（alpha diversity）从NFE组到FE组呈现显著的梯度下降趋势（例如香农指数（Shannon index）：NFE组为3.68±0.34，ME组为3.02±1.02，FE组为0.84±0.54；p<0.05）。β多样性（beta diversity）分析显示，不同急性加重表型的微生物群落聚类存在显著差异（置换多元方差分析（permutational multivariate analysis of variance, PERMANOVA）R²=0.19，p=0.001）。FE组以假单胞菌门（Pseudomonadota）的显著优势为特征（相对丰度达72.25%），该菌门丰度与急性加重频率呈正相关（r=0.536，p<0.001）。与之相反，链球菌属（Streptococcus）及厚壁菌门（Bacillota）、拟杆菌门（Bacteroidota）内的其他共生类群在FE组中丰度显著降低，且与急性加重频率呈负相关。12种与急性加重耐受相关的类群（其中83.3%隶属于厚壁菌门/拟杆菌门）与预测一秒用力呼气容积占预计值百分比（FEV1% pred）呈正相关（r=0.322~0.483，p<0.05）。α多样性指数与急性加重频率呈显著负相关（r=-0.84~-0.86，p<0.001），但与肺量测定指标（spirometric measures）无显著关联。
结论：本研究结果阐明了慢性阻塞性肺疾病患者中，随急性加重频率梯度变化的气道微生物群失调特征。易发生急性加重的表型以微生物多样性丧失、假单胞菌门扩张及潜在保护性共生类群耗竭为典型特征。上述微生物组特征可作为识别高危患者的潜在生物标志物，也可为未来开发靶向微生物组的治疗策略提供参考。