多组学分析揭示肺炎支原体肺炎小鼠模型中的免疫-代谢特征及肠道微生物生物标志物

Abstract

Simple SummaryMycoplasma pneumoniaepneumonia (MPP) is a common respiratory infection with poorly understood systemic pathogenesis. Using a murine model, we integrated lung transcriptomics, lung metabolomics, fecal 16S rRNA sequencing, and fecal metabolomics to systematically characterize host responses toMycoplasma pneumoniae(MP) infection. We found that MP infection activates pulmonary inflammatory pathways (NF-κB, Th17) while disrupting fatty acid metabolism. Notably, three pulmonary metabolites (3′-AMP, CMP-Neu5Ac, and 4-imidazoleacrylic acid) showed significant correlations with key transcript-level inflammatory cytokines (IL-18,IL-33,IL-12A), implicating metabolic reprogramming in pulmonary inflammation. Concurrent fecal 16S rRNA and metabolomic analyses showed marked gut dysbiosis (Marvinbryantiaenrichment) and altered metabolites linked to lung transcript-level cytokines, providing evidence for gut–lung axis involvement. Our multi-omics dissection offers a systems-level view of immune–metabolic crosstalk in MPP and identifies candidate biomarkers from both the pulmonary and intestinal compartments, with potential applications in diagnosis and therapeutic targeting.Mycoplasma pneumoniaepneumonia (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 × 108CCU/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-inflammatoryIL-18/IL-33, whereas upregulated 4-imidazol