Clinical lipidomics in bacterial sepsis: a systematic review of serum and plasma evaluations

Clinical Snapshot

Key Findings

• P Value: Not reported at the review level

• Effect Size: No pooled effect size reported; narrative synthesis only. Directional trends: TAG consistently elevated; LPC consistently depleted; PC bidirectional; SM bidirectional with a trend toward elevation; ceramides elevated

• Primary Outcome: Identification of reproducible lipid biomarker candidates in serum and plasma of adult bacterial sepsis patients, with characterisation of directional trajectories and inter-matrix differences in diagnostic versus prognostic utility

• Nnt Or Sensitivity: No NNT, sensitivity, specificity, or AUC values reported at the review level; individual study diagnostic performance metrics not synthesised

• Confidence Interval: Not reported — no quantitative pooling performed

Clinical Application

Clinical lipidomics remains a research-grade tool. Untargeted lipidomics requires specialised mass spectrometry infrastructure, bioinformatics expertise, and standardised pre-analytical workflows not currently available in routine Australian clinical laboratories. Targeted lipidomic panels for specific species (e.g., LPC, TAG) may be more feasible for near-term clinical translation if validated in prospective cohorts. In Australia, sepsis management is guided by the Surviving Sepsis Campaign guidelines as adopted by ANZICS and the Australian Commission on Safety and Quality in Health Care (ACSQHC). Current PBS-listed biomarkers for sepsis (procalcitonin, CRP, lactate) do not include lipidomic panels. The TGA has not approved any lipidomic diagnostic device for sepsis. RACGP and ACRRM guidelines do not currently reference lipidomics in sepsis management. Australian ICU and emergency medicine networks (ANZICS, ACEM) would need to lead prospective validation studies before any lipidomic biomarker could be considered for clinical integration. The findings of this review are relevant to Australian researchers and clinicians as a horizon-scanning evidence summary, but do not yet support practice change. Adult patients admitted to emergency departments or intensive care units with confirmed or suspected bacterial sepsis, where blood-based biomarker profiling is being considered for diagnostic stratification or prognostic risk assessment

Abstract

BACKGROUND: Lipid metabolism plays a central role in host-pathogen interactions and immune regulation during bacterial sepsis, with its dysregulation contributing to organ failure and mortality. Blood-based lipidomics has emerged as a promising approach for identifying diagnostic and prognostic biomarkers in sepsis. However, discrepancies in lipid profiles between serum and plasma remain a major challenge for clinical translation. This systematic review synthesizes lipidomic evidence from serum and plasma in bacterial sepsis patients to identify reproducible lipid biomarkers, evaluate methodological heterogeneity and assess associations with clinical outcomes. METHODS: A systematic search of five databases (Scopus, Pubmed, Ovid MEDLINE, Web of Science and Google Scholar) identified nine eligible studies published between 2016 and 2025 that applied untargeted or targeted lipidomics on human serum and plasma samples from adult bacterial sepsis patients (PROSPERO: CRD420251086177). RESULTS: Across both matrices, reproducible candidate lipid biomarkers included triacylglycerols (TAG), phosphatidylcholines (PC), lysophosphatidylcholines (LPC), sphingomyelins (SM) and ceramides. Synthesized findings revealed characteristically distinct directional trajectories: consistent elevation of TAG, bidirectional shifts of PC, depletion of LPC, bidirectional shifts of SM and elevation of SM. Preliminary trend within the literature indicates that serum-based studies more frequently captured prognostic alterations, whereas plasma-based studies often focused on diagnostic discrimination. Substantial heterogeneity was observed in sample handling, lipid extraction protocols and analytical platforms. CONCLUSIONS: Overall, both matrices offer valuable clinical insights, though these apparent differences in diagnostic or prognostic utility may reflect primary study designs rather than intrinsic matrix superiorities. Methodological heterogeneity limits reproducibility, highlighting the need for standardized workflows to enable translation of sepsis lipid biomarkers.

References

1. 1.Ahmad, N. S., Ibrahim, R., Tan, T. L., Baharum, S. N., & Sekawi, Z. (2026). Clinical lipidomics in bacterial sepsis: a systematic review of serum and plasma evaluations. Metabolomics: Official Journal of the Metabolomic Society. https://doi.org/10.1016/j.cbi.2014.06.029