Format

Send to

Choose Destination
Am J Pathol. 2019 Sep;189(9):1797-1813. doi: 10.1016/j.ajpath.2019.05.021.

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.

Author information

1
Sarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina; Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
2
Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, Texas.
3
Sarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina.
4
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
5
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: willisms@iu.edu.

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.

PMID:
31439155
PMCID:
PMC6723233
[Available on 2020-09-01]
DOI:
10.1016/j.ajpath.2019.05.021

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center