Frontiers in cellular and infection microbiology · 2026
Metagenomic next-generation sequencing reveals airway microbial dysbiosis and functional alterations in Legionella pneumophila pneumonia.
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Zhang Hao, Zou Wenjing, Wu Weiwei, Xu Jun, Ren Lijun, Liu Mengying, Sun Di, Liu Jia, Yu Yanzhe, Yu Min, Ding Jingjing
Аннотация
BACKGROUND: Legionella pneumonia (LP), primarily caused by Legionella pneumophila, is a clinically important subtype of community-acquired pneumonia (CAP) associated with substantial morbidity and mortality. However, the microbial characteristics and functional profiles of LP remain insufficiently understood.
METHODS: In this study, metagenomic next-generation sequencing (mNGS) was used to compare airway microbial communities between patients with LP and those with non-Legionella CAP.
RESULTS: A total of 60 patients were included, comprising 23 patients with LP patients and 37 patients with non-Legionella CAP patients. Airway microbial diversity and composition differed between groups, although the between-group effect size was modest and residual confounding could not be excluded. The LP group showed higher relative abundance of Legionella pneumophila and selected opportunistic species, whereas several oral commensal-associated species were relatively enriched in non-Legionella CAP. In the pooled 60-patient cohort, selected microbial species were associated with inflammatory and clinical severity markers; these associations were not disease-specific and do not imply causality. Inferred functional profiles also differed between groups. Exploratory machine-learning models showed high internal discriminatory performance, with XGBoost yielding the highest mean AUC, but the small cohort and lack of external validation limit conclusions regarding diagnostic utility.
CONCLUSIONS: In this small retrospective cohort, LP was associated with differences in airway microbial composition and inferred functional potential compared with a heterogeneous non-Legionella CAP group. Because the study was observational, the groups differed in important clinical characteristics, and the pooled association analyses were not disease-specific, the findings should be considered exploratory and hypothesis-generating. The reproducibility and diagnostic value of microbiota-derived features require confirmation in larger, prospectively collected, independent cohorts.
METHODS: In this study, metagenomic next-generation sequencing (mNGS) was used to compare airway microbial communities between patients with LP and those with non-Legionella CAP.
RESULTS: A total of 60 patients were included, comprising 23 patients with LP patients and 37 patients with non-Legionella CAP patients. Airway microbial diversity and composition differed between groups, although the between-group effect size was modest and residual confounding could not be excluded. The LP group showed higher relative abundance of Legionella pneumophila and selected opportunistic species, whereas several oral commensal-associated species were relatively enriched in non-Legionella CAP. In the pooled 60-patient cohort, selected microbial species were associated with inflammatory and clinical severity markers; these associations were not disease-specific and do not imply causality. Inferred functional profiles also differed between groups. Exploratory machine-learning models showed high internal discriminatory performance, with XGBoost yielding the highest mean AUC, but the small cohort and lack of external validation limit conclusions regarding diagnostic utility.
CONCLUSIONS: In this small retrospective cohort, LP was associated with differences in airway microbial composition and inferred functional potential compared with a heterogeneous non-Legionella CAP group. Because the study was observational, the groups differed in important clinical characteristics, and the pooled association analyses were not disease-specific, the findings should be considered exploratory and hypothesis-generating. The reproducibility and diagnostic value of microbiota-derived features require confirmation in larger, prospectively collected, independent cohorts.