Abstract
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis with underlying circulatory cellular and metabolic abnormalities associated with higher mortality rates. However, a detailed understanding of sepsis is still limited. The present study reports the differences in the metabolic profile of serum samples of patients with sepsis compared to healthy controls using Nuclear Magnetic Resonance (NMR) spectroscopy. The study also compares the NMR metabolomics on day zero of admission among sepsis survivors (those who survived till day seven) and sepsis non-survivors (those who succumbed on day zero). Furthermore, the different metabolites in serum were analysed by univariate and multivariate analysis, ROC analysis, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) methods. Metabolites with VIP score (>1·0) were considered as potential biomarker/s to discriminate sepsis survivors from non- survivors at day zero. Data showed that phenylalanine was significantly higher in sepsis patients compared to healthy controls, whereas isoleucine, valine and histidine were significantly lower in sepsis patients compared to healthy controls. Also, non-survivors had higher serum levels of creatine, phosphocreatine, choline, betaine, tyrosine, histidine and phenylalanine concentrations than survivors. These findings suggest that the metabolic alterations at day zero may predict the survival of patients with sepsis. The significant differences seen in metabolites concentration of amino acids, phospholipids and creatine may be used as early prognostic markers to discriminate non-survivors from survivors of sepsis patients at day zero. Our findings indicate that the metabolite alterations are associated with the progression of the disease.
Highlights
Sepsis is one of the important global health problems
The present study reports the differences in the metabolic profile of serum samples of patients with sepsis compared to healthy controls using Nuclear Magnetic Resonance (NMR) spectroscopy
We investigated the discriminatory ability of metabolic fingerprints in early prediction of sepsis survivors and non-survivors within 24 hours and describe the evolution of metabolic fingerprints in patients with sepsis using NMR spectroscopy based metabolomics
Summary
Sepsis is one of the important global health problems. It is a life threatening condition leading to organ dysfunction as a result of host immune dysregulation in response to infection. A population-based analysis by Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, estimated the global, regional, and national incidence of sepsis and mortality in about 195 countries for the years 1990 to 2017. Proton (1H) Nuclear Magnetic Resonance (1H-NMR) is one of the major analytical approaches of metabolomics, where a large number of metabolites in serum or urine or tissue is quantitatively analysed in a single step. It promises an immense potential for early diagnosis and for understanding the pathogenesis of the disease[6].The literature on NMR spectroscopy based metabolomics approach to develop a personalized predictive model for septic patients has increased significantly in the last decade. We investigated the discriminatory ability of metabolic fingerprints in early prediction of sepsis survivors and non-survivors within 24 hours and describe the evolution of metabolic fingerprints in patients with sepsis using NMR spectroscopy based metabolomics
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