Exploring plasma metabolomic changes in sepsis: a clinical matching study based on gas chromatography–mass spectrometry

Abstract

Background: Sepsis is a deleterious systemic inflammatory response to infection, and despite advances in treatment, the mortality rate remains high. We hypothesized that plasma metabolism could clarify sepsis in patients complicated by organ dysfunction.Methods: Plasma samples from 31 patients with sepsis and 23 healthy individuals of comparable age, gender, and body mass index (BMI) were collected. Plasma metabolites were detected through gas chromatography-mass spectrometry (GC-MS), and relevant metabolic pathways were predicted using the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway database. Student's t-test was employed for statistical analysis. In addition, to explore sepsis organ dysfunction, plasma samples of sepsis patients were further analyzed by metabolomics subgroup analysis according to organ dysfunction.Results: A total of 222 metabolites were detected, which included 124 metabolites with statistical significance between the sepsis and control groups. Among these, we found 26 were fatty acids, including 3 branched fatty acids, 10 were saturated fatty acids, and 13 were unsaturated fatty acids that were found in sepsis plasma samples but not in the controls. In addition, 158 metabolic pathways were predicted, 74 of which were significant. Further subgroup analysis identified seven metabolites in acute kidney injury (AKI), three metabolites in acute respiratory distress syndrome (ARDS), seven metabolites in sepsis-induced myocardial dysfunction (SIMD), and four metabolites in acute hepatic ischemia (AHI) that were significantly different. The results showed that the sepsis samples exhibited extensive changes in amino acids, fatty acids, and tricarboxylic acid (TCA)-cycle products. In addition, three metabolic pathways-namely, energy metabolism, amino acid metabolism, and lipid metabolism-were downregulated in sepsis patients. Conclusions:The downregulated energy, amino acid, and lipid metabolism found in our study may serve as a novel clinical marker for the dysregulated internal environment, particularly involving energy metabolism, which results in sepsis.

Dietary fatty acid metabolism: New insights into the similarities of lipid metabolism in humans and hamsters

“…These type of FA have been studied in the scientific literature in relation to their presence in food, especially in dairy products and food of ruminant origin ( Vlaeminck et al, 2006 ) and have been detected in human specific tissues as skin or brain ( Mika et al, 2016 ). Few works detected their presence in human plasma ( Lin et al, 2020 ) and, to the best of our knowledge, besides our previous work ( Berriozabalgoitia et al, 2021 ), only one ( Mika et al, 2016 ) determined their concentration. The data obtained by these authors are in the same level of ours, and coincide in the fact that anteisoheptadecanoic acid is the BCFA that is present in the highest percent.…”

Patient Stratification in Sepsis: Using Metabolomics to Detect Clinical Phenotypes, Sub-Phenotypes and Therapeutic Response

“…It is suggested that mitochondrial dysfunction in sepsis leads to the accumulation of glycolysis and tricarboxylic acid (TCA) cycle metabolites such as lactate, pyruvate and citric acid [ 16 ], and the pathways which lead to the accumulation of these metabolites are shown in Figure 1 . Several studies in Table 1 consistently showed that sepsis patients had increased levels of glycolysis metabolites including lactate [ 21 , 22 , 23 , 24 , 25 ] and pyruvate [ 21 , 26 ] compared to healthy controls [ 21 , 22 , 23 ] or those with SIRS [ 24 , 25 , 26 ]. Lin et al showed elevation of seven TCA metabolites as well as two TCA cycle derivatives including DL-gamma-methylketoglutaramate isomer and dimethyl fumarate in sepsis compared to healthy controls [ 21 ], which suggests upregulation of the TCA cycle in septic patients.…”

“…Several studies in Table 1 consistently showed that sepsis patients had increased levels of glycolysis metabolites including lactate [ 21 , 22 , 23 , 24 , 25 ] and pyruvate [ 21 , 26 ] compared to healthy controls [ 21 , 22 , 23 ] or those with SIRS [ 24 , 25 , 26 ]. Lin et al showed elevation of seven TCA metabolites as well as two TCA cycle derivatives including DL-gamma-methylketoglutaramate isomer and dimethyl fumarate in sepsis compared to healthy controls [ 21 ], which suggests upregulation of the TCA cycle in septic patients. Interestingly, Kauppi et al and Jaurila et al showed that the TCA cycle metabolite citric acid was significantly reduced in septic patients compared to healthy controls [ 26 , 27 ].…”

Delirium and Psychiatric Sequelae Associated to SARS-CoV-2 in Asymptomatic Patients With Psychiatric History and Mild Cognitive Impairment as Risk Factors: Three Case Reports

“…In addition, a septic condition might represent a deleterious systemic inflammatory response to infection. Lin et al ( 55 ) hypothesized that plasma metabolism could clarify sepsis complicated by organ dysfunction, as it may probably occur in COVID-19 patients.…”