P016 Lipidomics in ulcerative colitis reveal disruption of mucosal lipid composition associated with the disease state

Abstract

BACKGROUND: Several genetic, bacterial, and environmental factors appear to lead to the onset of ulcerative colitis (UC). Moreover, UC seems to be associated with alterations in lipid metabolism, and a disruption of the balance between pro and anti-inflammatory molecules. Membrane bioactive lipids modulate the immune response by functioning as intra- and intercellular signaling molecules. However, there are only few studies describing the mucosal lipid bio-signatures during IBD. Therefore, our study aims to characterize mucosal lipid profiles in treatment-naive UC patients and deep remission UC patients, compared to healthy subjects. METHODS: Newly diagnosed treatment-naive UC patients (n = 21), UC patients in deep remission (n = 12), and healthy volunteers (n = 14) were recruited. The state of deep remission was defined by histological and immunological remission demonstrated by a normalized TNF-α gene expression. Mucosa biopsies were collected by colonoscopy. Lipid analysis was performed by means of ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). In total, 220 lipids from 11 lipid classes were identified and included for data analysis. RESULTS: Sixteen lipids showed significant concentration differences between the study groups reflecting the inflammatory state. The majority of significantly up- or down- regulated lipids were phosphatidylethanolamines (PE), and ceramides (Cer). Data analysis revealed that changes in Cer18:1/24:1, Cer18:1/24:0, and PE38:3 were most prominent between the groups. The concentration of Cer18:1/24:1 was highly increased in UC patients' inflamed mucosa compared with UC patients' healed mucosa, whereas, PE38:3 is exclusively present in UC patients' colonic mucosa (both treatment naive and remission state patients). Furthermore, Cer18:1/24:0 was elevated in a stepwise manner from control to remission, and active UC. CONCLUSION(S): Lipid analysis in UC revealed alterations in the mucosal lipid composition. In this study, we report several lipids, which might be involved in the inflammatory response and pathogenesis seen in IBD. The PE38:3 is especially interesting in a pathophysiological context since it is found in both active colitis and deep remission but not healthy controls.