Abstract

The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

Highlights

  • Crohn’s disease (CD) is an inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract

  • In this study, we focused on a twin cohort, described previously [2], [17], that includes healthy twin pairs, concordant pairs and discordant pairs

  • The patients with CD were further differentiated depending on whether inflammation was primarily localized in the ileum (ICD) or in the colon (CCD) [2], [17]

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Summary

Introduction

Crohn’s disease (CD) is an inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract. The exact etiology of CD is unknown, but both the host genotype and environmental factors play a role, and it is known that disease induction requires the presence of bacteria. No specific pathogen has been defined as a causative agent, but individuals with CD have an imbalance or ‘dysbiosis’ of their intestinal microbiota, or microbiome [1], [2]. Dysbiosis in turn leads to a breakdown in the detente relationship between the microbiome and the host immune system, through unknown mechanisms. Diagnostic and monitoring tools for CD are currently inadequate. For clinical applications, none of the current markers stand-alone and they are used in conjunction and as a supplement to endoscopy. More accurate tools are needed for early diagnosis of CD; in particular non-invasive approaches that can be used in place of endoscopy

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