Exploring the circulating metabolome of sepsis: metabolomic and lipidomic profiles sampled in the ambulance

Abstract

Background: Sepsis is defined as a dysfunctional host response to infection. The diverse clinical presentations of sepsis pose diagnostic challenges and there is a demand for enhanced diagnostic markers for sepsis as well as an understanding of the underlying pathological mechanisms involved in sepsis. From this perspective, metabolomics has emerged as a potentially valuable tool for aiding in the early identification of sepsis that could highlight key metabolic pathways and underlying pathological mechanisms. Objective: The aim of this investigation is to explore the early metabolomic and lipidomic profiles in a prospective cohort where plasma samples (n = 138) were obtained during ambulance transport among patients with infection according to clinical judgement who subsequently developed sepsis, patients who developed non-septic infection, and symptomatic controls without an infection. Methods: Multiplatform metabolomics and lipidomics were performed using UHPLC–MS/MS and UHPLC–QTOFMS. Uni- and multivariable analysis were used to identify metabolite profiles in sepsis vs symptomatic control and sepsis vs non-septic infection. Results: Univariable analysis disclosed that out of the 457 annotated metabolites measured across three different platforms, 23 polar, 27 semipolar metabolites and 133 molecular lipids exhibited significant differences between patients who developed sepsis and symptomatic controls following correction for multiple testing. Furthermore, 84 metabolites remained significantly different between sepsis and symptomatic controls following adjustment for age, sex, and Charlson comorbidity score. Notably, no significant differences were identified in metabolites levels when comparing patients with sepsis and non-septic infection in univariable and multivariable analyses. Conclusion: Overall, we found that the metabolome, including the lipidome, was decreased in patients experiencing infection and sepsis, with no significant differences between the two conditions. This finding indicates that the observed metabolic profiles are shared between both infection and sepsis, rather than being exclusive to sepsis alone.