Analysis of the Plasma Metabolome after Trauma, Novel Circulating Sphingolipid Signatures, and In-Hospital Outcomes
Open Access
- 13 January 2021
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American College of Surgeons
- Vol. 232 (3), 276-287e1
- https://doi.org/10.1016/j.jamcollsurg.2020.12.022
Abstract
Background Trauma is the leading cause of death and disability for individuals under age 55. Many severely injured trauma patients experience complicated clinical courses despite appropriate initial therapy. We sought to identify novel circulating metabolomic signatures associated with clinical outcomes following trauma. Study design Untargeted metabolomics and circulating plasma immune mediator analysis was performed on plasma collected during 3 post-injury time periods (-6) among the top 50 metabolites. Clustering of sphingolipid patterns identified 3 patient subclasses: nonresponders (no time-dependent change in sphingolipids, n = 41), sphingosine/sphinganine-enhanced (n = 24), and glycosphingolipid-enhanced (n = 21). Compared with the sphingolipid-enhanced subclasses, nonresponders had longer mean length of stay, more ventilator days, higher MOD scores, and higher circulating levels of proinflammatory immune mediators IL-6, IL-8, IL-10, MCP1/CCL2, IP10/CXCL10, and MIG/CXCL9 (all p < 0.05), despite similar Injury Severity Scores (p = 0.12). Conclusions Metabolomic analysis identified broad alterations in circulating plasma sphingolipids after blunt trauma. Circulating sphingolipid signatures and their association with both clinical outcomes and circulating inflammatory mediators suggest a possible link between sphingolipid metabolism and the immune response to trauma.Keywords
Funding Information
- National Institutes of Health
This publication has 49 references indexed in Scilit:
- A genomic storm in critically injured humansThe Journal of Experimental Medicine, 2011
- Polymorphisms in the toll-like receptor 9 gene associated with sepsis and multiple organ dysfunction after major blunt traumaBritish Journal of Surgery, 2011
- The outs and the ins of sphingosine-1-phosphate in immunityNature Reviews Immunology, 2011
- Metabolite profiles and the risk of developing diabetesNature Medicine, 2011
- Low Prevalence of “Ideal Cardiovascular Health” in a Community-Based PopulationJournal of the American College of Cardiology, 2011
- Sphinganine-1-phosphate protects kidney and liver after hepatic ischemia and reperfusion in mice through S1P1 receptor activationLaboratory Investigation, 2010
- An Adequately Robust Early TNF-α Response Is a Hallmark of Survival Following Trauma/HemorrhagePLOS ONE, 2009
- Sphingolipids in inflammation: pathological implications and potential therapeutic targetsBritish Journal of Pharmacology, 2009
- Sphingosine-1-phosphate in the plasma compartment regulates basal and inflammation-induced vascular leak in miceJCI Insight, 2009
- Racial differences in coronary artery calcification are not attributed to differences in lipoprotein particle sizes: The Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) StudyAmerican Heart Journal, 2007