Serum metabolomics in a Helicobacter hepaticus mouse model of inflammatory bowel disease reveal important changes in the microbiome, serum peptides, and intermediary metabolism

J Proteome Res. 2012 Oct 5;11(10):4916-26. doi: 10.1021/pr300429x. Epub 2012 Sep 27.

Abstract

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the bowel. The etiology remains unknown, but IBD is immune-driven and multiple factors including genetic, environmental, and microbiological components play a role. Recombinase-activating gene-2-deficient (Rag2(-/-)) mice infected with Helicobacter hepaticus (H. hepaticus) have been developed as an animal model to imitate naturally occurring inflammatory events and associated key features of chronic inflammatory responses in humans. In this study, we have combined mass spectrometry-based metabolomics and peptidomics to analyze serum samples of Rag2(-/-) mice infected with H. hepaticus. Metabolomics profiling revealed that H. hepaticus infection dramatically changed numerous metabolite pathways, including tryptophan metabolism, glycerophospholipids, methionine-homocysteine cycle, citrate cycle, fatty acid metabolism and purine metabolism, with the majority of metabolites being down-regulated. In particular, there were notable effects of gut microflora on the blood metabolites in infected animals. In addition, the peptidomics approach identified a number of peptides, originating from proteins, including fibrinogen, complement C4, and alpha-2-macroglobulin, with diverse biological functions with potentially important implications for the progress of IBD. In summary, the strategy of integrating a relevant animal model and sensitive mass spectrometry-based profiling may offer a new perspective to explore biomarkers and provide mechanistic insights into IBD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood Proteins / metabolism*
  • Cluster Analysis
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Energy Metabolism
  • Fatty Acids / metabolism
  • Helicobacter Infections / blood*
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / microbiology
  • Helicobacter hepaticus*
  • Inflammatory Bowel Diseases / blood*
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / microbiology
  • Lipid Metabolism
  • Metagenome
  • Mice
  • Mice, 129 Strain
  • Mice, Knockout
  • Molecular Sequence Data
  • Multivariate Analysis
  • Peptide Fragments / blood
  • Peptide Fragments / chemistry
  • Peptide Mapping
  • Principal Component Analysis
  • Tandem Mass Spectrometry

Substances

  • Blood Proteins
  • DNA-Binding Proteins
  • Fatty Acids
  • Peptide Fragments
  • Rag2 protein, mouse