Integrated serum metabolomics reveals severity-associated exploratory metabolic signatures in burn patients

To systematically characterize the serum metabolome of burn patients using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Patients were stratified by burn severity based on total body surface area (TBSA; ≥30% vs. <30%). Exploratory metabolic signatures and candidate biomarkers associated with burn severity were investigated.

Peripheral serum samples were collected from patients with TBSA ≥30% (n=33), TBSA <30% (n=28), and healthy controls (n=18). Serum metabolomic profiling was performed by UPLC-MS/MS. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to identify differential metabolites. Pathway enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database via MetaboAnalyst. Receiver operating characteristic curve (ROC) analysis was performed to preliminarily evaluate the discriminatory performance of exploratory candidate biomarkers.

Distinct metabolic dysregulation was observed between burn severity groups. Compared with the healthy control group, twenty-three significantly altered metabolites were identified in patients with TBSA ≥30%, while thirty-one metabolites were altered in patients with TBSA <30%. Severe burns (TBSA ≥30%) predominantly disrupted amino acid and glycerophospholipid metabolism, whereas moderate burns (<30%) mainly involved lipid-related pathways. Patients with TBSA ≥30% exhibited perturbations across a broader range of metabolic pathways. ROC analysis identified nine exploratory candidate biomarkers (area under the curve [AUC] >0.8) in patients with TBSA ≥30% and eight in patients with TBSA <30%, suggesting preliminary discriminatory potential within the current cohort for distinguishing metabolic alterations associated with different burn severities.

Burn severity may be associated with distinct serum metabolomic signatures. Key pathways and exploratory candidate biomarkers associated with burn severity-related metabolic alterations were identified. These findings provide a metabolomics-based reference framework for future studies investigating burn severity-associated metabolic alterations and may support future mechanistic and translational research in burn care.