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

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.

IBD metabonomics predicts phenotype, disease course, and treatment response

“…These phenotypic findings have also been observed with MSbased lipidomic [21] (i.e., a subset of the metabolome) and metabonomic studies [20] and may discriminate between patients with flares of UC, patients with quiescent UC, and control individuals in multivariate modeling. Here 220 different lipids and 177 metabolites were identified, respectively, but the highest significant variation was observed within the sphingolipids, phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and a range of amino acids.…”

Impaired Butyrate Induced Regulation of T Cell Surface Expression of CTLA-4 in Patients with Ulcerative Colitis

“…Further, UC patients with mild to severe disease activity have been shown to express low levels of genes involved in butyrate uptake and oxidation [ 36 ]. Also, a recent pathway enrichment analysis showed altered butyrate metabolism in UC patients [ 37 ], and our group demonstrated that butyrate more potently down-regulates gene expression of inflammatory pathways in non-inflamed controls than in inflamed tissue of UC patients [ 38 ]. It should be noted that the effect of butyrate may differ according to the local microenvironment.…”

Metabolic Profiling of Plasma in Patients with Irritable Bowel Syndrome after a 4-Week Starch- and Sucrose-Reduced Diet

“…The GC-MS analysis was performed with Agilent 6890 GC equipment and a fused silica capillary column (10 m × 0.18 mm I.D.) with a chemically bonded 0.18 µm DB5-MS stationary phase (J&W Scientific, Folsom, CA, USA) as previously described [ 38 ].…”