Multi-omics analysis of human plasma reveals reprogramming of tryptophan metabolism associated with inflammation in Mycoplasma pneumoniae pneumonia in children

OBJECTIVES: Mycoplasma pneumoniae pneumonia (MPP) poses a severe threat to the health of children, yet its molecular alterations and pathogenic mechanisms remain poorly understood. In this study, we performed a multi-omics analysis to investigate the interactions between Mycoplasma pneumoniae and the pediatric host. METHODS: We enrolled children with MPP and healthy controls (HC), constructing two independent cohorts. Plasma samples were analyzed using untargeted metabolomics and Olink proteomics to identify key metabolites and associated pathways. Targeted metabolomics was applied to validate and quantify metabolites within the most affected pathway. Correlation analyses were conducted between metabolites, cytokines, and clinical parameters. RESULTS: Dysregulation of amino acid, lipid, and carbohydrate metabolism was observed in MPP patients compared with HC. Among these, tryptophan metabolism was the most prominently affected pathway. The rate-limiting enzyme indoleamine 2,3-dioxygenase 1 significantly increased across HC, general MPP (GMPP), and severe MPP (SMPP). Targeted metabolomics analysis in both cohorts verified the reprogramming of tryptophan metabolism, with reduced tryptophan levels, increased kynurenine metabolites, and decreased indole derivatives. Correlation analysis revealed broad and strong associations of these metabolites with cytokines (e.g., IFN-γ, CXCL10, IL-6, TNFSF/TNFRSF) and clinical parameters (e.g., CRP, PCT, LDH, D-Dimer). Furthermore, reductions in indole derivatives were also observed between SMPP and GMPP. CONCLUSIONS: The reprogramming of tryptophan metabolism in pediatric MPP patients is characterized by upregulated kynurenine pathway and downregulated indole pathway, with potential regulatory crosstalk with inflammation. Our findings provide evidence for the role of tryptophan metabolism in MPP, highlighting its potential as novel therapeutic targets.