Pulmonary mucoid <i>Pseudomonas aeruginosa</i> infection and association with higher species richness and stronger inflammatory immune response

The mucoid phenotype of <i>Pseudomonas aeruginosa</i> (PA) is regarded as a comprehensive adaptive stress response to difficult environmental circumstances. However, there is little knowledge about the relationship between the prevalence of mucoid PA and species richness and immune inflammatory response. A case-control study was conducted in hospitalized patients with pulmonary infections caused by mucoid and non-mucoid PA. Sputum samples were subjected to 16S rDNA sequencing to characterize microbial diversity and taxonomic composition, while serum levels of TNF-α, IL-6, IL-8, IL-10, and IL-17 were measured using enzyme-linked immunosorbent assays. Subsequent statistical analysis using R 4.0 revealed significant correlations between differentially abundant microbial taxa and cytokine profiles. Compared to the non-mucoid PA group, the mucoid PA group demonstrated significantly higher α-diversity indices in terms of species richness, as indicated by the Chao1 (<i>P</i> = 0.0015) and Observed-species metrics (<i>P</i> = 0.0014). Furthermore, distinct β-diversity patterns were observed between the two groups (<i>P</i> < 0.05). LefSe analysis revealed significant enrichment of <i>Veillonella</i> spp., <i>Haemophilus</i> spp., <i>Porphyromonas</i> spp., <i>Prevotella</i> spp., <i>Actinomyces</i> spp., <i>Lactobacillus</i> spp., and <i>Rothia</i> spp. in the mucoid PA group, while <i>Stenotrophomonas</i> spp., <i>Acinetobacter</i> spp., <i>Parvimonas</i> spp., and <i>Serratia</i> spp. dominated in the non-mucoid PA group. The mucoid PA infections showed marked elevation of IL-8 (<i>P</i> = 0.0137), TNF-α (<i>P</i> = 0.0048), IL-10 (<i>P</i> = 0.0042), IL-17 (<i>P</i> = 0.0220), and IL-6 (<i>P</i> = 0.0001). Spearman correlation revealed <i>Veillonella</i> spp./<i>Rothia</i> spp./<i>Porphyromonas</i> spp./<i>Prevotella</i> spp. positively correlated with IL-10/TNF-α/IL-17/IL-6, whereas <i>Haemophilus</i> spp. showed a negative relationship with IL-17. <i>Stenotrophomonas</i> spp. exhibited strong negative correlations with IL-10/IL-6, and <i>Serratia</i> spp. was inversely associated with TNF-α in non-mucoid PA infections. Clinically distinct microbial ecosystems in mucoid PA correlate with exacerbated inflammation. This phenotype-driven dichotomy provides actionable biomarkers for stratified antimicrobial/immunomodulatory therapies in chronic lung disease.IMPORTANCEThis study holds significant clinical and scientific importance, as it elucidates the critical differences between mucoid and non-mucoid <i>Pseudomonas aeruginosa</i> (PA) infections in pulmonary patients. By demonstrating that mucoid PA infections are associated with distinct microbial ecosystems (higher species richness and different taxonomic compositions) and more severe inflammatory responses (elevated TNF-α, IL-6, IL-8, IL-10, and IL-17), the research provides crucial insights into phenotype-specific pathogenesis. The identified correlations between specific bacterial species (e.g., <i>Veillonella/Rothia</i> with pro-inflammatory cytokines) offer potential biomarkers for clinical stratification. These findings are particularly valuable for developing targeted therapeutic strategies, as they suggest mucoid PA infections may require different antimicrobial/immunomodulatory approaches compared to non-mucoid variants. The study bridges an important knowledge gap in understanding how bacterial phenotypic adaptation influences host-microbiome interactions and disease outcomes in chronic lung infections.