Lipidomic Profiling of Plasma and Erythrocytes From Septic Patients Reveals Potential Biomarker Candidates

Abstract

Background:Sepsis remains the primary cause of death from infection, despite advances in modern medicine. The identification of reliable diagnostic biomarkers for the early detection of this disease is critical and may reduce the mortality rate as it could allow early treatment. The purpose of this study was to describe the changes in the plasma and red cells blood lipidome profiling of patients diagnosed with sepsis and septic shock with the aim to identify potentially useful metabolic markers.Methods:Lipids from plasma and erythrocytes from septic patients (n = 20) and healthy controls (n = 20) were evaluated by electrospray ionization quadrupole time-of-flight mass spectrometry, and the fatty acid composition of the phospholipids fraction of erythrocytes was determined by gas chromatography. The data were treated with multivariate data analysis, including principal component analysis and (orthogonal) partial least squares discriminant analysis.Results:Potential biomarkers including lysophosphatidylcholines (lyso-PCs) and sphingomyelin (SMs) with specific fatty acid chains were identified. Both Lyso-PCs and SMs were downregulated, whereas the saturated and unsaturated phosphatidylcholines (PCs) were upregulated in the plasma and erythrocytes of septic patients. An increase in oleic acid (C18:1 n-9) accompanied by a decrease in the unsaturation index as well as in the levels on n-3 polyunsaturated fatty acids was observed in erythrocytes phospholipids patients as compared with healthy controls.Conclusions:These results suggest that lipidome profiling has great potential in discovering potential clinical biomarkers for sepsis and helping to understand its underlying mechanisms.

Metabolomic Insights Into the Synergistic Effect of Biapenem in Combination With Xuebijing Injection Against Sepsis

“…The perturbed lipid metabolism including reduced lysophospholipids (LPLs) metabolism, increased PCs metabolism, elevated FFAs metabolism, and decreased sphingolipids metabolism as reflective of systemic changes resulted from inflammatory response and oxidative stress in sepsis (Sevastou et al, 2013). Our results were consistent with previous studies (Mecatti et al, 2018). Decreased LysoPCs might enhance the production of lysophosphatidic acids (Tokumura, 2002), which induced an immune response by activating various immune cells (Gräler and Goetzl, 2002).…”

Lipidomic profile and candidate biomarkers in septic patients

“…In concluding this review, we can say that altered lipid profiles, along with the progress of diseases, should provide new insights that will enable a better understanding of the physiopathology of sepsis, contributing new possibilities for effective diagnoses and therapies. The current review deals with the lipid molecules that are upregulated or down-regulated during the early stages of sepsis, as shown in the data presented in the present review and in earlier work of our research group [39]. Based on those aspects, we suggest that replenishing the protective molecules that are down-regulated in sepsis while withdrawing the elevated deleterious factors may lead to the discovery of new therapies for improving survival in septic patients; a goal that has been elusive for decades.…”

“…Patients with sepsis present low concentrations of n-6 and n-3 PUFAs and a high n-6/n-3 ratio and that is associated with high mortality [35][36][37][38]. An increase in oleic acid (C18:1 n-9) accompanied by a decrease in the unsaturation index as well as in the levels of n-3 PUFA was observed in erythrocyte phospholipids of septic patients as compared to healthy controls [39]. Arachidonic acid metabolism is also markedly affected in patients with sepsis.…”

“…Those results were supported by our group in a clinical study which observed important alterations in lipid metabolism in patients with sepsis, specifically including LPCs and sphingomyelin (SMs). Both LPCs and SMs were downregulated, whereas the saturated and unsaturated PCs were upregulated in the plasma and erythrocytes of septic patients [39]. Previous studies have also demonstrated an increase in circulating phospholipase A2 type II (snp-PLA2) in patients with severe infection [43,44].…”

“…A reduced LPS-induced release of AA and the COXassociated AA metabolites, 11-HETE, PGE2, and TXB2 was apparent in septic patients [40]. Also, decreased lysophosphatidylcholine (LPC) levels and increased ceramide (Cer) species rates in plasma are commonly associated with sepsis [37][38][39][40][41]. An investigation of sepsis from peritonitis using a swine model monitored changes in hemodynamic, blood chemistry, and inflammatory markers.…”