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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
- Source :
- Am J Pathol
- Publication Year :
- 2019
- Publisher :
- American Society for Investigative Pathology, 2019.
-
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), β-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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Arginine
Swine
Ileum
digestive system
Article
Pathology and Forensic Medicine
Jejunum
Sepsis
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Animals
Metabolomics
Pseudomonas Infections
skin and connective tissue diseases
Muscle, Skeletal
Lung
business.industry
digestive, oral, and skin physiology
Skeletal muscle
Metabolism
medicine.disease
Small intestine
Disease Models, Animal
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Liver
030220 oncology & carcinogenesis
Pseudomonas aeruginosa
Female
sense organs
business
Metabolic Networks and Pathways
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Am J Pathol
- Accession number :
- edsair.doi.dedup.....e38ca533f2e6b0d726c0a801592fafe9