Metabolomic Approaches in Sepsis Diagnosis and Prognosis

Metabolomic profiling has emerged as a powerful tool for improving the diagnosis and prognosis of sepsis by capturing dynamic changes in small-molecule metabolites that reflect host–pathogen interactions, organ dysfunction and treatment response. Both targeted and untargeted strategies using technologies such as liquid chromatography–mass spectrometry, gas chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy enable the quantification of amino acids, lipids, energy metabolites and other analytes in blood, urine and other biofluids. In diagnostic applications, metabolomics can distinguish sepsis from noninfectious systemic inflammatory states and identify subphenotypes such as direct versus indirect acute respiratory distress syndrome. In prognostic settings, metabolic signatures have been shown to predict short-term mortality, organ failure trajectories and responsiveness to resuscitation. Integrative analyses that combine metabolomics with proteomic or cytokine profiling further illuminate disrupted pathways—such as amino acid catabolism, fatty acid oxidation and glycerophospholipid turnover—that underpin sepsis pathophysiology. Despite challenges in standardising sample preparation, data processing and inter-study comparability, these advances herald a shift towards precision monitoring and personalised intervention in critically ill patients worldwide.

Research from Nature Portfolio

Studies employing quantitative metabolomic workflows have delineated prognostic markers in severe septic shock. In one foundational pilot investigation, targeted mass spectrometry was used to measure plasma acylcarnitines, amino acids, glycerophospholipids and sphingolipids in patients stratified by 28-day and 90-day survival. Reduced levels of unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines, together with perturbations in the kynurenine pathway, emerged as predictors of mortality when combined with clinical variables. Another analysis tracked metabolite concentration changes between admission and 48 hours post-resuscitation, revealing that shifts in glycerophospholipids and alanine correlated with responsiveness to therapy, as assessed by changes in organ failure scores. These investigations highlight how specific lipidome and amino-acid signatures can inform risk stratification and guide early therapeutic decisions.

Metabolomic Approaches in Sepsis Diagnosis and Prognosis publication trend

The graph below shows the total number of articles in metabolomic approaches in sepsis diagnosis and prognosis across all publications each year (not limited to Nature Index journals).

Technical terms

Metabolomics: The comprehensive study of small-molecule metabolites in biological samples.

Targeted metabolomics: Quantitative analysis of a predefined panel of metabolites.

Untargeted metabolomics: Global profiling aimed at detecting as many metabolites as possible without prior selection.

Glycerophospholipids: A class of membrane phospholipids involved in cell structure and signalling.

Sphingolipids: Lipid molecules that play key roles in cell signalling and membrane stability.

Lysophosphatidylcholines: Derivatives of phosphatidylcholines implicated as inflammatory and metabolic biomarkers.

References

1. A targeted metabolomics approach for sepsis-induced ARDS and its subphenotypes. Critical Care (2023).
2. Targeted metabolomics for discrimination of systemic inflammatory disorders in critically ill patients. Journal of Lipid Research (2012).
3. Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach. Scientific Reports (2016).
4. Characterization of a metabolomic profile associated with responsiveness to therapy in the acute phase of septic shock. Scientific Reports (2017).
5. Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis. Journal of Translational Medicine (2022).
6. Lipid oxidation dysregulation: an emerging player in the pathophysiology of sepsis. Frontiers in Immunology (2023).
7. Integration of metabolic and inflammatory mediator profiles as a potential prognostic approach for septic shock in the intensive care unit. Critical Care (2015).