Crohn's disease: a biomarker approach in assessing disease state and the efficacy of dietary intervention

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal disease resulting from an excessive immune response to intestinal microflora in genetically predisposed individuals. There is mounting evidence to suggest that the personalisation of diets to specific genotypes may be able to modulate the incidence and severity of disease in the IBD population. The move towards human dietary intervention studies is inevitable. It is therefore imperative that accurate and non-invasive methods for the evaluation and monitoring of an individual's disease state are identified and optimised. The aim of this study was to optimise the monitoring of disease development during mouse experiments, and develop biomarker investigation methods for assessing disease state and the efficacy of dietary interventions, with respect to IBD inflammation, for future human studies. This study investigated metabonomic and transcriptomic approaches to biomarker analysis for disease state identification in IBD mouse models. The aims of the study were twofold. The first aim concerned the analysis of nuclear magnetic resonance spectroscopy (NMR) as a suitable tool for the identification of biomarkers in biofluids, examining both individual biomarker methodology and pattern recognition analysis. The second aim addressed the use of pattern recognition analysis of gene expression profiles of spleen tissue to identify biomarkers associated with intestinal inflammatory events. This study has identified two individual biomarkers of intestinal inflammation from NMR analysis of urine for further validation: allantoin and sucrose. Multiple regression analysis (MRA) of binned NMR spectra was identified as an effective method of NMR pattern recognition analysis. The transcriptomic biomarker approach used correlation analysis to compare gene expression profiles with intestinal inflammation. Eight probes were identified as significantly correlated with a histological injury score (HIS). This study has developed and validated several biomarker analysis strategies that could be applied to human studies. Overall, MRA was found to be a valuable tool for biomarker pattern recognition identification and analysis. Both metabonomics and transcriptomics proved to be useful screening tools to identify biomarker profiles in IBD mouse models. The research has provided a critical foundation for identifying relevant biomarker profiles of accessible human tissues to support human dietary intervention studies related to the amelioration of symptoms associated with IBD.