Distinct Airway Microbiome States in Mycoplasma pneumoniae: Positive and Negative COPD Exacerbations in Elderly Patients
Xuejun Zhang
Puer Hospital of Traditional Chinese Medicine, Puer, China.
Jinrui Gu
Puer Hospital of Traditional Chinese Medicine, Puer, China.
Xuejin Li
Puer Hospital of Traditional Chinese Medicine, Puer, China.
Zexiu Wang
Puer Hospital of Traditional Chinese Medicine, Puer, China.
Mingyue Su
Puer Hospital of Traditional Chinese Medicine, Puer, China.
Hanlin Ma
Puer Hospital of Traditional Chinese Medicine, Puer, China.
Menghua Li
Puer Hospital of Traditional Chinese Medicine, Puer, China.
Xuequan He
Puer Hospital of Traditional Chinese Medicine, Puer, China.
Liwen Dong
Puer Hospital of Traditional Chinese Medicine, Puer, China.
Guiling Li *
Puer Hospital of Traditional Chinese Medicine, Puer, China.
*Author to whom correspondence should be addressed.
Abstract
Background: Chronic obstructive pulmonary disease (COPD) is frequently complicated by infection-associated exacerbations, but how Mycoplasma pneumoniae (MP) shapes airway microbial ecology in this setting is unclear.
Methods: In a single-center cross-sectional study, we enrolled 58 elderly participants from southwestern China: healthy controls (HealthyControl), stable COPD with negative MP (COPD_Stable_MPneg), acute exacerbation without MP (COPD_AE_MPneg), and acute exacerbation with MP (COPD_AE_MPpos). Sputum underwent 16S rRNA (V3–V4) sequencing with DADA2-based amplicon sequence variant inference. Using phyloseq, microeco and DESeq2, we assessed alpha/beta diversity, taxonomic composition, differentially abundant genera and FAPROTAX-predicted functions.
Results: Compared with HealthyControl, all COPD groups showed reduced Chao1 richness and Shannon diversity, with the lowest diversity and greatest within-group Bray–Curtis dissimilarity in COPD_AE_MPneg, indicating progressive “microbial simplification” and destabilization. HealthyControl sputum was dominated by oral commensals (Streptococcus, Veillonella, Neisseria, Prevotella, Haemophilus, Rothia). COPD_Stable_MPneg retained this oral-like architecture but with enrichment of Corynebacterium and depletion of Moraxella. COPD_AE_MPneg exhibited the most pronounced dysbiosis, with broad depletion of health-associated genera and enrichment of Limosilactobacillus, consistent with collapse of a commensal network rather than overgrowth of a single pathogen. COPD_AE_MPpos showed a narrower pattern, mainly decreased Moraxella and Pseudarcobacter. FAPROTAX predictions revealed higher contributions of chemoheterotrophy, fermentation and “gut-like” functions (human_gut, mammal_gut, human_pathogens_gastroenteritis), particularly in COPD_AE_MPneg.
Conclusions: In elderly COPD patients, airway dysbiosis is characterized by loss of diversity, disruption of an oral-like community and emergence of gut-like, pathogen-enriched profiles. MP-negative exacerbations display the most extensive commensal loss and functional reprogramming, whereas MP-positive episodes show a distinct but more restricted perturbation, underscoring the ecological heterogeneity of COPD exacerbations.
Keywords: Chronic obstructive pulmonary disease, destabilization, airway dysbiosis, ecological heterogeneity