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

Abstract

Simple Summary Mycoplasma pneumoniae pneumonia (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 to Mycoplasma 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 (Marvinbryantia enrichment) 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.