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. 2025 Apr 26;21(3):59.
doi: 10.1007/s11306-025-02255-x.

Untargeted lipidomics profiling provides novel insights into pediatric patients with sepsis: an exploratory study

Reyihangu Awuti #  1 , Jiayi Bai #  1 , Ye Cheng #  1 , Weili Yang  1 , Zimei Cheng  1 , Hetian Zhou  1 , Guoyun Su  2 , Kexin Wang  3 , Yaodong Wang  1 , Tingyan Liu  1 , Ying Liu  4 , Weiming Chen  1 , Hehe Chen  5 , Guoping Lu  6   7   8 , Caiyan Zhang  9
Affiliations

Untargeted lipidomics profiling provides novel insights into pediatric patients with sepsis: an exploratory study

Reyihangu Awuti et al. Metabolomics. .

Abstract

Introduction: The plasma lipidome has emerged as an important indicator for assessing host metabolic and immune status in sepsis. While previous studies have largely examined specific lipid class changes in adults sepsis, comprehensive investigations into plasma lipidomic alterations in pediatric sepsis are limited. This study aimed to characterize the plasma lipidome in pediatric sepsis using a metabolomics-based exploratory approach, providing insights into pathophysiological mechanisms and potential biomarkers.

Methods: A retrospective study was conducted on pediatric patients with sepsis admitted to the pediatric intensive care unit (PICU). Untargeted lipidomics analysis using ultra-performance liquid chromatography coupled with Orbitrap mass spectrometry (UPLC-Orbitrap) was performed to compare metabolomic profiles between non-infected control patients and sepsis patients.

Results: Compared to controls, plasma lipid levels in sepsis patients decreased by 33.3%, increased by 20.2%, and remained unchanged in 46.5% of cases. A total of 1,257 differential lipids were identified in sepsis patients, with 24 lipids showing significant associations with pSOFA scores. In the recovery and deterioration subgroups, 186 differential lipids were identified, with triglyceride (TG) representing the highest proportion at 16.4%. Notably, 15 lipids with significant statistical differences were identified as differential lipid species through a comparison of those associated with pSOFA scores and those linked to sepsis prognosis. Fatty acid (FA) levels were significantly elevated in the sepsis group compared to controls, with arachidonic acid (FA(20:4)) showing the most significant increase (P < 0.001).

Conclusion: Alterations in plasma lipid profiles among children with sepsis reflect disease severity, systemic inflammatory responses, and sepsis prognosis. These findings underscore the prognostic potential of lipidomics and its value in understanding sepsis pathophysiology.

Keywords: Fatty acid; Pediatric sepsis; Plasma lipidome; Untargeted lipidomics.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: Ethical approval for the study was provided by Ethics Committee of Children’s Hospital of Fudan University ([2024] No. 116). Written informed consent was obtained from all parents or their surrogates of studied children. Consent for publication: All authors consent to the publication of this manuscript.

Figures

Fig. 1
Fig. 1
Alterations in the Plasma Lipidome of Sepsis Patients. a PCA score plot of the control and sepsis groups. X-axis and Y-axis show the first and second principal component with the percentage of explained variance respectively, and the ellipse represents the 95% confidence interval. b Volcano plot of differential lipids based on univariate analysis.The x-axis represents the log2-transformed fold change values, the y-axis represents the log10-transformed P-values, and the points represent lipid species. c Pie chart of differential lipids based on univariate analysis. d Unsupervised hierarchical clustering heatmap of lipid classes in the control and sepsis groups (Only the lipids with differences were analyzed). e Correlation heatmap of lipid classes in the control and sepsis groups (Only the lipids with differences were analyzed)
Fig. 2
Fig. 2
Changes in plasma lipidome closely associated with disease severity. a Pie chart of differential lipids of the control and sepsis groups based on PLS-DA results. b Bar plot of lipids correlated with pSOFA scores. c Scatter plot of lipids correlated with pSOFA scores. d Correlation heatmap of lipids correlated with pSOFA scores
Fig. 3
Fig. 3
Host response to infection linked to changes in the plasma lipidome. a Correlation heatmap of differential lipids and laboratory indicators. b Scatter plot of lipids correlated with laboratory indicators
Fig. 4
Fig. 4
Alterations in the plasma lipidome of sepsis patients associated with a worse prognosis. a Boxplot of lipid classes in the sepsis recovery and deterioration groups. b Pie chart of differential lipids between the sepsis recovery and deterioration groups. c Unsupervised hierarchical clustering heatmap of differential lipids between the sepsis recovery and deterioration groups. d, e In all, 15 lipids with the significant statistical difference between the lipids associated with pSOFA score and those associated with sepsis prognosis were found in the Venn intersection of the comparison (The bar chart displays only the top five differential lipids). f Bar chart of laboratory indicators in the sepsis recovery and deterioration groups. Statistically significant differences are indicated, with *P < 0.05, **P < 0.01, ***P < 0.001
Fig. 5
Fig. 5
Changes in the fatty acid profile of sepsis patients. a Stacked bar chart of fatty acids comparing the control and sepsis groups. b Boxplots of fatty acids in the control and sepsis groups. c Boxplots of fatty acids in the recovery and deterioration groups. d Correlation heatmap of fatty acids and cholesterol esters in sepsis patients. e Scatter plot of fatty acids and cholesterol esters correlation. Statistically significant differences are indicated, with *P < 0.05, **P < 0.01, ***P < 0.001
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References

    1. Balamuth, F., Scott, H. F., Weiss, S. L., Webb, M., Chamberlain, J. M., Bajaj, L., Depinet, H., Grundmeier, R. W., Campos, D., Deakyne Davies, S. J., Simon, N. J., Cook, L. J., & Alpern, E. R. (2022). Validation of the pediatric sequential organ failure assessment score and evaluation of third international consensus definitions for Sepsis and septic shock definitions in the pediatric emergency department. JAMA Pediatr, 176(7), 672–678. 10.1001/jamapediatrics.2022.1301 - PMC - PubMed
    1. Barber, G., Tanic, J., & Leligdowicz, A. (2023). Circulating protein and lipid markers of early sepsis diagnosis and prognosis: A scoping review. Current Opinion in Lipidology, 34(2), 70–81. 10.1097/mol.0000000000000870 - PubMed
    1. Bauer, M., Gerlach, H., Vogelmann, T., Preissing, F., Stiefel, J., & Adam, D. (2020). Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019- results from a systematic review and meta-analysis. Critical Care, 24(1), 239. 10.1186/s13054-020-02950-2 - PMC - PubMed
    1. Cambiaghi, A., Díaz, R., Martinez, J. B., Odena, A., Brunelli, L., Caironi, P., Masson, S., Baselli, G., Ristagno, G., Gattinoni, L., de Oliveira, E., Pastorelli, R., & Ferrario, M. (2018). An innovative approach for the integration of proteomics and metabolomics data in severe septic shock patients stratified for mortality. Scientific Reports, 8(1), 6681. 10.1038/s41598-018-25035-1 - PMC - PubMed
    1. Caterino, M., Gelzo, M., Sol, S., Fedele, R., Annunziata, A., Calabrese, C., Fiorentino, G., D’Abbraccio, M., Dell’Isola, C., Fusco, F. M., Parrella, R., Fabbrocini, G., Gentile, I., Andolfo, I., Capasso, M., Costanzo, M., Daniele, A., Marchese, E., Polito, R., Russo, R., Missero, C., Ruoppolo, M., & Castaldo, G. (2021). Dysregulation of lipid metabolism and pathological inflammation in patients with COVID-19. Scientific Reports, 11(1), 2941. 10.1038/s41598-021-82426-7 - PMC - PubMed

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