Mucosal Metabolomic Profiling and Pathway Analysis Reveal the Metabolic Signature of Ulcerative Colitis

Joseph Diab,Jon Florholmen,Guro Forsdahl,Terkel Hansen,Rasmus Goll,Hans Stenlund,Thomas Moritz,Einar Jensen

doi:10.3390/metabo9120291

Abstract

The onset of ulcerative colitis (UC) is characterized 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. This study aims to explore the mucosal metabolomic profile in UC patients, and to define the UC metabolic signature. Treatment- naïve UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopies. 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. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acyl carnitine, and amino acid profiles. Several pathways were found perturbed according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as tryptophan metabolism) to fatty acid metabolism, namely linoleic and butyrate. These metabolic changes during UC reflect the homeostatic disturbance in the gut, and highlight the importance of system biology approaches to identify key drivers of pathogenesis which prerequisite personalized medicine.

Highlights

Inflammatory bowel diseases (IBD) are chronic, relapsing inflammatory disorders in the gastrointestinal tract that affect around 0.3% of the population in Europe and North America with increasing worldwide incidence [1]
This study aimed to explore the mucosal metabolomic profile in treatment-naïve ulcerative colitis (UC) patients compared to treated UC patients in deep remission and to healthy subjects
The present report provides an in-depth description of the mucosal metabolome in UC via a high-throughput metabolomic analysis of colon biopsies taken from UC treatment-naïve patients, UC patients in state of deep remission, and healthy subjects

Summary

Introduction

Inflammatory bowel diseases (IBD) are chronic, relapsing inflammatory disorders in the gastrointestinal tract that affect around 0.3% of the population in Europe and North America with increasing worldwide incidence [1]. The two major forms of IBD, ulcerative colitis (UC) and Crohn’s disease (CD), are characterized by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host–microbe interaction [2]. Metabolites 2019, 9, 291 between these components yield a network effect, defined as ‘IBD interactome’, which results in an overwhelming complexity [3]. This complexity cannot be solved by studying one component in isolation from the others. Multiomics approaches were suggested as a tool to unravel the IBD interactome, and to improve the patient stratification strategies toward personalized medicine [3,6]

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