Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State

Abstract

Background The onset of ulcerative colitis (UC) is associated with alterations in lipid metabolism and a disruption of the balance between pro- and anti-inflammatory molecules. Only a few studies describe the mucosal lipid biosignatures during active UC. Moreover, the dynamics of lipid metabolism in the remission state is poorly defined. Therefore, this study aims to characterize mucosal lipid profiles in treatment-naïve UC patients and deep remission UC patients compared with healthy subjects. Methods Treatment-naïve 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 defined 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. Results The relative concentration of 122 and 36 lipids was altered in UC treatment-naïve patients and UC remission patients, respectively, compared with healthy controls. The highest number of significant variations was in the phosphatidylcholine (PC), ceramide (Cer), and sphingomyelin (SM) composition. Multivariate analysis revealed discrimination among the study groups based on the lipid profile. Furthermore, changes in phosphatidylethanolamine(38:3), Cer(d18:1/24:0), and Cer(d18:1/24:2) were most distinctive between the groups. Conclusion This study revealed a discriminant mucosal lipid composition pattern between treatment-naïve UC patients, deep remission UC patients, and healthy controls. We report several distinctive lipids, which might be involved in the inflammatory response in UC, and could reflect the disease state.

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

“…Although the inclusion criteria for remission patients was mucosal healing and immunological remission [37], the present work reveals a distinct metabolome in UC deep remission patients with respect to healthy controls and active UC patients. This comes in alignment with previously published data which reports a distinct mucosal lipid composition fingerprint in UC deep remission patients compared with healthy controls and treatment-naïve UC patients [38]. Consequently, from a clinical point of view, these findings supports the emerging importance of 'Omics' analysis in improving the current scoring system, monitoring the disease progression and improving the treatment strategies [39].…”

VEGF-B ablation in pancreatic β-cells upregulates insulin expression without affecting glucose homeostasis or islet lipid uptake

“…Lipid content from 150 pancreatic islets per group were analyzed by ultra-fast liquid chromatography-mass spectrometry (UFLC-MS) based lipidomics analysis and high-performance liquid chromatography by the Swedish Metabolomics Center at the Swedish University of Agricultural Sciences. In detail, the lipid content were extracted following a modified Folch protocol [47][48][49] . In detail, 200 µL of extraction buffer (2:1 v/v chloroform:methanol) including internal standards (tripalmitin-1,1,1-13C3 and 16:0-d31 ceramide) were added to 150 pancreatic islets.…”

“…After all samples www.nature.com/scientificreports www.nature.com/scientificreports/ had been analyzed, the instrument was switched to negative mode and a second injection of each sample was performed. The LC-MS analysis of the lipid extracts were performed as described in Diab et al 47 .…”

Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis

“…The strength of this prospective designed, combined discovery and validation study is that we have RHI med (IQR)* 6 (2-10) 6 (4-11) 14 (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) UCCS score 1-year med (IQR) 0 (0-0) 0 (0-0) 0 (0-8) retrospectively searched for and validated biomarkers for treatment at debut of UC, using a broad search of clinical, histological and analytical factors including mucosal immune transcripts. Moreover, this is part of the transomic Advanced Study of Inflammatory Bowel disease (ASIB) study where parallel studies of the epigenome, transcriptome, proteome and metabolome are ongoing [33,[41][42][43][44][45]. .This transomic approach at debut of UC will be performed and correlated to long-term clinical outcome.…”