Identification of Metabolic Changes in Ileum, Jejunum, Skeletal Muscle, Liver, and Lung in a Continuous I.V. Pseudomonas aeruginosa Model of Sepsis Using Nontargeted Metabolomics Analysis

Abstract

Sepsis is a multiorgan disease affecting the ileum and jejunum (small intestine), liver, skeletal muscle, and lung clinically. The specific metabolic changes in the ileum, jejunum, liver, skeletal muscle, and lung have not previously been investigated. Live Pseudomonas aeruginosa, isolated from a patient, was given via i.v. catheter to pigs to induce severe sepsis. Eighteen hours later, ileum, jejunum, medial gastrocnemius skeletal muscle, liver, and lung were analyzed by nontargeted metabolomics analysis using gas chromatography/mass spectrometry. The ileum and the liver demonstrated significant changes in metabolites involved in linoleic acid metabolism: the ileum and lung had significant changes in the metabolism of valine/leucine/isoleucine; the jejunum, skeletal muscle, and liver had significant changes in arginine/proline metabolism; and the skeletal muscle and lung had significant changes in aminoacyl-tRNA biosynthesis, as analyzed by pathway analysis. Pathway analysis also identified changes in metabolic pathways unique for different tissues, including changes in the citric acid cycle (jejunum), b-alanine metabolism (skeletal muscle), and purine metabolism (liver). These findings demonstrate both overlapping metabolic pathways affected in different tissues and those that are unique to others and provide insight into the metabolic changes in sepsis leading to organ dysfunction. This may allow therapeutic interventions that focus on multiple tissues or single tissues once the relationship of the altered metabolites/metabolism to the underlying pathogenesis of sepsis is determined.

Effect of molecular hydrogen treatment on Sepsis‐Associated encephalopathy in mice based on gut microbiota

“…In the past, sepsis was thought to occur mainly due to tissue and organ damage caused by an excessive inflammatory response. However, according to the latest studies, the pathogenesis of sepsis may be accompanied by common and specific metabolic changes in multiple tissues and organs (liver, lung, intestine, bone, and ilium muscle), suggesting that metabolic mechanisms may potentially underlie the pathogenesis of sepsis 21 . Therefore, we screened the coaltered metabolites that showed significant differences in serum and brain tissue to explore the changes in metabolic levels in the SAE group and explored the changes in their expression levels in brain tissue after molecular hydrogen treatment (Table 2).…”

Dichloroacetate reverses sepsis-induced hepatic metabolic dysfunction

“…The liver is an important metabolic and immune organ due to its role in nutrient metabolism and production of acute phase proteins. However, our understanding of transcriptional alterations and subsequent metabolic phenotypes elicited by sepsis still remain limited ( Seymour et al, 2013 ; Ilaiwy et al, 2019 ; Dahn et al, 1995 ; Levy et al, 1968 ; Han et al, 2004 ). Furthermore, the mechanisms by which dichloroacetate (DCA) elicits hepatic metabolic changes in response to sepsis are completely unknown.…”

Dichloroacetate reverses sepsis-induced hepatic metabolic dysfunction

“…The liver is an important metabolic and immune organ due to its role in nutrient metabolism and production of acute phase proteins. However, our understanding of transcriptional alterations and subsequent metabolic manifestations elicited by sepsis still remain limited 16,[25][26][27][28] . Furthermore, the effects of DCA at restoring hepatic metabolic function in the context of sepsis is completely unknown.…”