Multi-Omics Profiling Identifies Immune-Metabolic Signatures and Gut Microbial Biomarkers in a Murine Model of Mycoplasma pneumoniae Pneumonia.

Mycoplasma pneumoniae pneumonia (MPP) is driven by excessive host immune responses and metabolic dysregulation, yet its systemic pathogenesis remains poorly understood. Here, we established a murine MPP via MP (1 × 108 CCU/mL), which faithfully recapitulates clinical features, including interstitial pneumonia, elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and increased alveolar macrophage abundance. Integrating lung transcriptomics and metabolomics, we found that MP infection activates pro-inflammatory cytokines (e.g., cytokine-cytokine receptor interaction, Th17 differentiation, NF-κB signaling) while disrupting fatty acid metabolism. Correlative analyses revealed that downregulated 3'-AMP and CMP-Neu5Ac correlated with elevated pro-inflammatory IL-18/IL-33, whereas upregulated 4-imidazoleacrylic acid correlated with reduced anti-inflammatory IL-12A base on transcriptomic data, suggesting that metabolic reprogramming may exacerbate pulmonary inflammation. Furthermore, 16S rRNA sequencing and fecal metabolomics revealed marked microbiota dysbiosis, enrichment of Marvinbryantia, and depletion of beneficial taxa, alongside altered fecal metabolites, with correlations linking gut microbial shifts and metabolite changes to lung transcript-level inflammatory cytokines, supporting a gut-lung axis involvement in MPP. Collectively, our multi-omics dissection provides a systems-level view of immune-metabolic crosstalk in MP infection, offering mechanistic insights and potential biomarkers for improved diagnosis and therapeutic targeting.