Plasma metabolomic profiling identifies candidate biomarkers associated with sepsis diagnosis and mortality prediction

Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection; its early diagnosis and mortality prediction remain challenging, and conventional markers (CRP, PCT) have limited sensitivity and specificity. We aimed to characterize the plasma metabolome of sepsis and identify candidate metabolic biomarkers for diagnosis and 30-day mortality prediction. In this retrospective, single-center study, plasma from 30 healthy volunteers, 107 sepsis/septic shock patients and 19 non-septic ICU patients was analyzed by non-targeted LC-MS/MS and stratified into discovery (n=86) and replication (n=70) cohorts. Differential metabolites were defined by VIP > 1 and p < 0.05, with Benjamini–Hochberg q-values reported. Diagnostic and prognostic performance was assessed by ROC analysis and compared with CRP, PCT and the SOFA score; survival was analyzed by Kaplan–Meier with the log-rank test. A longitudinal subset was sampled on days 1, 3 and 5. Multivariate analyses identified nine significantly dysregulated metabolites in sepsis patients versus both controls and non-septic ICU patients. Three—3-methoxyanthranilate, docosahexaenoic acid and N-acetyl-beta-alanine—showed particular significance, with alterations in amino-acid, carbohydrate and lipid metabolism, and were elevated in non-survivors. Longitudinal analysis revealed distinctive temporal patterns for 3-methoxyanthranilate and N-acetyl-beta-alanine. The combined panel showed diagnostic and prognostic performance that compared favorably with CRP, PCT and the SOFA score for sepsis differentiation and 30-day mortality. 3-methoxyanthranilate, docosahexaenoic acid and N-acetyl-beta-alanine are candidate metabolic biomarkers for sepsis diagnosis and prognosis. Given the modest, single-center sample, these exploratory, hypothesis-generating findings require confirmation in larger, multi-center cohorts and targeted metabolomic studies.