Metabolic footprint of sepsis and septic shock: A narrative review

Sepsis and septic shock are complex, heterogeneous syndromes associated with high morbidity and mortality despite advances in critical care management. Conventional biomarkers used in clinical practice lack specificity and prognostic accuracy to measure and monitor the dynamic metabolic abnormalities occurring in these conditions. Metabolomics, the comprehensive analysis of low-molecular weight metabolites, are powerful tools to define host metabolic responses to infection and inflammation. This review summarizes current concepts in metabolomic research in sepsis and septic shock, highlighting findings from both experimental models and human studies using nuclear magnetic resonance and mass spectrometry-based platforms. Key metabolic alterations involving energy metabolism, amino acids, lipids, mitochondrial function, and "microbial metabolism" biota-derived metabolites are discussed in relation to disease severity, organ dysfunction, and clinical outcomes. The integration of metabolomics with clinical parameters and other omics technologies holds promise for improving diagnosis, prognostication, and therapeutic stratification in sepsis, paving the way toward precision medicine approaches in critical care.