Sepsis-related metabolic changes in ileum, jejunum, skeletal muscle, liver and lung

ABSTRACT: Rationale: Sepsis is a multi-organ disease affecting the ileum and jejunum (small intestine),liver, skeletal muscle, and lung clinically. Recently, specific alterations in circulating metabolites have been found in patients with sepsis which are thought to contribute to the pathogenesis of disease. The specific metabolic changes in the ileum, jejunum, liver, skeletal muscle, and lung have not previously been investigated. Methods: Live Pseudomonas aeruginosa isolated from a patient was given via IV catheter to pigs to induce severe sepsis. Eighteen hours later, ileum, jejunum, medial gastrocnemius skeletal muscle, liver, and lung were harvested and flash frozen. Tissues were subsequently processed for non-targeted metabolomics analysis using gas chromatography/mass spectrometry. Results: After 18 hours of sepsis, the ileum and the liver demonstrated significant changes in metabolites involved in linoleic acid metabolism, the ileum and lung had significant changes in valine/leucine/isoleucine metabolism, 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 by pathway analysis. Pathway analysis also identified changes in metabolic pathways unique for different tissues, including changes in the citric acid cycle (jejunum), beta-alanine metabolism (skeletal muscle), and purine metabolism (liver). Conclusion: 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.

ORGANISM(S): Sus Scrofa Pig

TISSUE(S): Intestine, Liver, Lung, Muscle

DISEASE(S): Sepsis

SUBMITTER: Monte Willis  

PROVIDER: ST001190 | MetabolomicsWorkbench | Mon Dec 03 00:00:00 GMT 2018

REPOSITORIES: MetabolomicsWorkbench