The Landscape of Featured Metabolism-Related Genes and Imbalanced Immune Cell Subsets in Sepsis

Abstract

Sepsis is a heterogeneous disease state triggered by an uncontrolled inflammatory host response with high mortality and morbidity in severely ill patients. Unfortunately, the treatment effectiveness varies among sepsis patients and the underlying mechanisms have yet to be elucidated. The present aim is to explore featured metabolism-related genes that may become the biomarkers in patients with sepsis. In this study, differentially expressed genes (DEGs) between sepsis and non-sepsis in whole blood samples were identified using two previously published datasets (GSE95233 and GSE54514). A total of 66 common DEGs were determined, namely, 52 upregulated and 14 downregulated DEGs. The Gene Set Enrichment Analysis (GSEA) results indicated that these DEGs participated in several metabolic processes including carbohydrate derivative, lipid, organic acid synthesis oxidation reduction, and small-molecule biosynthesis in patients with sepsis. Subsequently, a total of 8 hub genes were screened in the module with the highest score from the Cytoscape plugin cytoHubba. Further study showed that these hub DEGs may be robust markers for sepsis with high area under receiver operating characteristic curve (AUROC). The diagnostic values of these hub genes were further validated in myocardial tissues of septic rats and normal controls by untargeted metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS). Immune cell infiltration analysis revealed that different infiltration patterns were mainly characterized by B cells, T cells, NK cells, monocytes, macrophages, dendritics, eosinophils, and neutrophils between sepsis patients and normal controls. This study indicates that metabolic hub genes may be hopeful biomarkers for prognosis prediction and precise treatment in sepsis patients.

Integrative single-cell RNA sequencing and metabolomics decipher the imbalanced lipid-metabolism in maladaptive immune responses during sepsis

“…Currently, there are still no effective treatment therapies to lower sepsis mortality due to the complex pathophysiology ( 27 , 28 ). Although sepsis is fundamentally associated with inflammation, recent studies have reported that metabolism, especially lipid metabolism, plays a critical role in the pathogenesis and pathophysiology of sepsis ( 23 , 29 ). Serum levels of the prostaglandins PGE 2 and PGD 2 , two eicosanoid lipid mediators, are found to be elevated in patients with sepsis, accompanying with increased COX-2 activity ( 30 ).…”

“…The rats were randomly divided into three groups: the control group, the sepsis group, and the SB203580-treated sepsis group. To establish a sepsis model, cecal ligation and puncture (CLP) were performed as previously described ( 23 ). SB203580 (500 μg/kg) was administered via the tail vein 30 minutes prior to sepsis induction, while the sepsis group received an equal volume of ddH2O in the same manner.…”

“…RNA was extracted from human blood samples and rat cardiac tissues as previously described ( 23 ). Following reverse transcription, the resulting products in each experimental group were subjected to PCR amplification.…”

Metabolomics meets systems immunology

“…For example, Zhu et al ( 2022 ) used high‐resolution untargeted metabolomics analysis to study influenza A virus subtype H1N1 (H1N1) infected patients and found an association between abnormal arginine metabolism produced by the virus and the immunity of the respiratory mucosa. She et al ( 2022 ) used untargeted metabolomics analysis to discover metabolic hub genes that may be biomarkers for precise therapy in sepsis patients. In their research, Ding et al ( 2021b ) used untargeted metabolomics analysis to identify glycerophospholipid (GPL) metabolism and glutamine and glutamate metabolism as potential key targets in HIV infection.…”

Analysis of metabolic disturbances attributable to sepsis-induced myocardial dysfunction using metabolomics and transcriptomics techniques

“…Mannose metabolism, amino sugar metabolism, starch metabolism, unsaturated fatty acid biosynthesis, platelet activation, and purine metabolism have some studies in sepsis ( Gao et al, 2015 ; Bakalov et al, 2016 ; Hwang et al, 2019 ; She et al, 2022 ). However, there are no relevant studies in Sepsis-induced myocardial dysfunction (SIMD).…”