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Poster presentations: Basic Science 2020

P003 Metabolomics for improved patient stratification in inflammatory bowel disease: Characterisation of the ulcerative colitis metabolome

J. Diab1, T. Hansen1, R. Goll2,3, H. Stenlund4, E. Jensen1, T. Moritz4,5, J. Florholmen2,3, G. Forsdahl1

1Department of Pharmacy, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, Tromsø, Norway, 2Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, Tromsø, Norway, 3Department of Medical Gastroenterology, University Hospital of North Norway, Tromsø, Norway, 4Department of Molecular Biology, Swedish Metabolomics Center, Umeå University, Umeå, Sweden, 5The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

Background

The onset of ulcerative colitis (UC) is characterised by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host-microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve the patient stratification strategies toward personalised medicine. This study aims to explore the mucosal metabolomic profile in treatment-naïve and deep remission UC patients, and to define the metabolic signature of UC.

Methods

Treatment-naive UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopy. The UC activity and the state of deep remission were assessed by endoscopy, histology, and by measuring TNF gene expression.

Metabolomic analysis was performed by combined gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). In total, 177 metabolites from 50 metabolic pathways were identified.

Results

Multivariate data analysis revealed a distinct metabolomic profile in inflamed mucosa taken from treatment- naïve UC patients compared with non-inflamed mucosa taken from UC remission patients and healthy controls. The mucosal metabolome in UC remission patients differed to a lesser extent from the healthy controls. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acylcarnitine, and amino acid profiles. Several metabolic pathways were perturbed, ranging from amino acid metabolism (such as tryptophan metabolism, and alanine, aspartate and glutamate metabolism) to antioxidant defence pathway (glutathione pathway). Furthermore, the pathway analysis revealed a disruption in the long-and short-chain fatty acid (LCFA and SCFA) metabolism, namely linoleic metabolism and butyrate metabolism.

Conclusion

The mucosal metabolomic profiling revealed a metabolic signature during the onset of UC, and reflected the homeostatic disturbance in the gut. The altered metabolic pathways highlight the importance of system biology approaches to identify key drivers of IBD pathogenesis which prerequisite personalised treatment.