Global metabolic phenotyping in an experimental laparotomy model of surgical trauma.

TitleGlobal metabolic phenotyping in an experimental laparotomy model of surgical trauma.
Publication TypeJournal Article
Year of Publication2011
AuthorsKinross JM, Alkhamesi N, Barton RH, Silk DB, Yap IKS, Darzi AW, Holmes E, Nicholson JK
JournalJ Proteome Res
Date Published2011 Jan 7
KeywordsAnimals, Biological Markers, Blood Chemical Analysis, Disease Models, Animal, Intraoperative Complications, Laparotomy, Least-Squares Analysis, Magnetic Resonance Spectroscopy, Male, Metabolomics, Metagenome, Multivariate Analysis, Phenotype, Principal Component Analysis, Rats, Rats, Wistar, Reproducibility of Results, Urine, Wounds and Injuries

Surgical trauma initiates a complex series of metabolic host responses designed to maintain homeostasis and ensure survival. (1)H NMR spectroscopy was applied to intraoperative urine and plasma samples as part of a strategy to analyze the metabolic response of Wistar rats to a laparotomy model. Spectral data were analyzed by multivariate statistical analysis. Principal component analysis (PCA) confirmed that surgical injury is responsible for the majority of the metabolic variability demonstrated between animals (R² Urine = 81.2% R² plasma = 80%). Further statistical analysis by orthogonal projection to latent structure discriminant analysis (OPLS-DA) allowed the identification of novel urinary metabolic markers of surgical trauma. Urinary levels of taurine, glucose, urea, creatine, allantoin, and trimethylamine-N-oxide (TMAO) were significantly increased after surgery whereas citrate and 2-oxoglutarate (2-OG) negatively correlated with the intraoperative state as did plasma levels of betaine and tyrosine. Plasma levels of lipoproteins such as VLDL and LDL also rose with the duration of surgery. Moreover, the microbial cometabolites 3-hydroxyphenylpropionate, phenylacetylglycine, and hippurate correlated with the surgical insult, indicating that the gut microbiota are highly sensitive to the global homeostatic state of the host. Metabonomic profiling provides a global overview of surgical trauma that has the potential to provide novel biomarkers for personalized surgical optimization and outcome prediction.

Alternate JournalJ. Proteome Res.
PubMed ID21105667