An untargeted metabolomic study using MALDI-mass spectrometry imaging reveals region-specific biomarkers associated with bowel inflammation

Abstract

IntroductionInflammatory bowel diseases (IBDs) are chronic immune driven intestinal disorders with marked metabolic alteration. Mass spectrometry imaging (MSI) enables the direct visualization of biomolecules within tissues and facilitates the study of metabolic changes. Integrating multiple spatial information sources is a promising approach for discovering new biomarkers and understanding biochemical alteration within the context of the disease.ObjectiveThis study evaluates the metabolomic changes in gut tissue samples from a preclinical model of spontaneous colitis, the HLA-B27/hβ2m transgenic rat, to uncover disease biomarkers.MethodsWe applied MSI to study the biochemical profile of bowel samples from HLA-B27/hβ2m transgenic and WT control rats in an unbiased manner. Statistical comparison was used to identify discriminative features. Some features were annotated using LC-MS/MS. The significance of these discriminative features was evaluated based on their distribution within histological layers and the presence of immune infiltration.ResultsWe identified spatially resolved changes in the metabolomic pattern of HLA-B27+ samples compared to WT controls. Out of the 275 discriminative features identified, 83 were annotated as metabolites. Two functional groups of discriminative metabolites were discussed as markers of gut barrier impairment and immune cell infiltration.ConclusionMS imaging’s spatial dimension provides insights into disease mechanisms through the identification of spatially resolved biomarkers.