Metabolic footprint of sepsis and septic shock: A narrative review

Abstract

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.

Keywords: Septic shock; Sepsis; Systemic inflammatory response syndrome; Metabolomics; Biomarkers

Core Tip: Sepsis remains a cause of significant morbidity and mortality despite recent advances. Moreover, patient’s response to therapy and clinical prognosis is often difficult to accurately predict. Given the heterogeneous and multifactorial nature of disease, broad therapeutic approaches often fail to reduce mortality. Thus, there is a critical need for a better understanding of these complex, multifactorial conditions driven by diverse biological insults and causes. Biomarkers such as procalcitonin, presepsin, interleukin-6, and C-reactive protein are frequently used in diagnosing and monitoring sepsis, but they are far from ideal. Human metabolic activity is extremely sensitive to the surrounding microenvironment, with metabolite profiles reflecting combined influences from transcriptional, translational, and environmental factors. Hence, metabolites are a highly promising class of biomarkers which may be exploited to detect disease presence, progression, and therapeutic response. Emerging data suggests that early introduction of metabolomic data into routine critical care practice may enable more precise severity identification, targeted therapeutic strategies, and improved outcomes for patients with sepsis and septic shock.