Non-severe burns induce a prolonged systemic metabolic phenotype indicative of a persistent inflammatory response post-injury

Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic co-morbidity and disease. To date, research has primarily focused on the systemic response to severe injury, with little in the literature reported on impact of non-severe injuries (<15% total burn surface area; TBSA). To elucidate the metabolic consequences of non-severe burn injury, longitudinal plasma was collected from adults (n=35) who presented at hospital with a non-severe burn injury at admission, and at 6 week follow up. A cross-sectional baseline sample was also collected from non-burn control participants (n=14). Samples underwent multiplatform metabolic phenotyping using 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry to quantify 112 lipoprotein and glycoproteins signatures and 852 lipid species from across 20 subclasses. Multivariate data modelling (Orthogonal projection to latent structures-discriminate analysis) revealed alterations in lipoprotein and lipid metabolism when comparing baseline control to hospital admission samples, with the phenotypic signature found to be sustained at follow up. Univariate (Mann-Whitney U) testing and OPLS-DA indicated specific increases in GlycB (p-value <1.0e-4), low density lipoprotein-2 subfractions (Variable importance in projection score; VIP >6.83e-1) and monoacyglyceride (20:4)(p-value <1.0e-4) and decreases in circulating anti-inflammatory high-density lipoprotein-4 subfractions (VIP >7.75e-1), phosphatidylcholines, phosphatidylglycerols, phosphatidylinositols and phosphatidylserines. The results indicate a persistent systemic metabolic phenotype that occurs even in cases of non-severe burn injury. The phenotype is indicative of an acute inflammatory profile which continues to be sustained post-injury, suggesting an impact on systems health beyond the site of injury. The phenotypes contained metabolic signatures consistent with chronic inflammatory states reported to have elevated incidence post-burn injury. Such phenotypic signatures may provide patient stratification opportunities, to identify individual responses to injury, personalise intervention strategies and improve acute care, reducing risk of chronic co-morbidity. ### Competing Interest Statement The authors have declared no competing interest. * AB100 : Apolipoprotein B100 ABA1 : Apolipoprotein B100/apolipoprotein A1 B.I.-LISA : Bruker IVDr lipoprotein subclass analysis CABIN : Randomised placebo-controlled trial of Celecoxib for acute burn inflammation CER : Ceramide CV-AUROC : Cross validated-area under the receiver operating characteristic DAG : Diacylglyceride DIRE : Diffusion and relaxation editing FFA : Free fatty acid H4A1 : HDL-4 apolipoprotein A1 HDA1 : HDL-associated apolipoprotein A1 HDL : High density lipoprotein hs-CRP : high sensitivity C-reactive protein ILDL : Intermediate low density lipoprotein IVDr : in vitro Diagnostics research L2AB : LDL-2-associated apolipoprotein B LC-QQQ-MS : Liquid chromatography-tandem mass spectrometry LDL : Low density lipoprotein LPC : Lysophosphatidylcholine LPE : Lysophosphatidylethanolamine LPG : Lysophosphatidylglycerol MAG : Monoacylglyceride MS : Mass spectrometry NMR : Nuclear magnetic resonance OPLS-DA : Supervised orthogonal projection to latent structures discriminant analysis PC : Phosphatidylcholine PCA : Principal component analysis PE : Phosphatidylethanolamine PI : Phosphatidylinositol PG : Phosphatidylglycerol PS : Phosphatidylserine QC : Quality control RSD : Relative standard deviation SM : Sphingomyelin SPC : Supramolecular phospholipid composite TAG : Triacylglyceride TBSA : Total burn surface area TSP : Sodium trimethylsilyl propionate-[2,2,3,3-2H4] VIP : Variable important in projection VLDL : Very low density lipoprotein