Distinct Airway Microbiome States in Mycoplasma pneumoniae: Positive and Negative COPD Exacerbations in Elderly Patients

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.