Int J Biol Sci 2022; 18(5):1813-1828. doi:10.7150/ijbs.67112 This issue

Research Paper

Lipidomic Trajectories Characterize Delayed Mucosal Wound Healing in Quiescent Ulcerative Colitis and Identify Potential Novel Therapeutic Targets

Jacob Tveiten Bjerrum1✉, Yulan Wang2✉, Jingtao Zhang2, Lene Buhl Riis3, Ole Haagen Nielsen1, Jakob Benedict Seidelin1

1. Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Denmark.
2. Singapore Phenome Centre, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
3. Department of Pathology, Herlev Hospital, University of Copenhagen, Denmark.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Bjerrum JT, Wang Y, Zhang J, Riis LB, Nielsen OH, Seidelin JB. Lipidomic Trajectories Characterize Delayed Mucosal Wound Healing in Quiescent Ulcerative Colitis and Identify Potential Novel Therapeutic Targets. Int J Biol Sci 2022; 18(5):1813-1828. doi:10.7150/ijbs.67112. Available from https://www.ijbs.com/v18p1813.htm

File import instruction

Abstract

Graphic abstract

Improving the long-term prognosis of ulcerative colitis (UC) requires sustained deep mucosal colonic healing with histologic remission, making the study of colonic tissue regeneration essential. In experimental colitis models, lipid metabolites are recognized as pivotal components of this process. This study aimed to describe the kinetics of wound healing and lipid metabolites engaged in regeneration in the normal colonic mucosa and how they are affected in UC to reveal new therapeutic targets. Experimental colonic wounds were created endoscopically in quiescent UC (n=21) and controls (n=9), and the healing process was surveilled by serial endoscopies and cross-sectional wound biopsies post-wounding. Biopsies were analyzed by liquid chromatography coupled with mass spectrometry. Endoscopic wound scores were significantly higher in UC at day two (p=0.001) and seven (p<0.0001) post-wounding, demonstrating a prolonged wound healing process. The wound scores were correlated with lipid mediators crucial for normal regeneration and sustained UC-specific changes in key phospholipids and eicosanoids, i.e., lysophosphatidylcholine, phosphatidylcholine, lysophosphatidic acid, phosphatidylglycerol, phosphatidylinositol, prostaglandin D2, and prostaglandin E1, were observed. A prolonged wound healing process is identified in quiescent UC with altered disease specific lipidomic trajectories providing potential novel therapeutic avenues for stimulating mucosal regeneration as an add-on to the traditional immune suppression treatment.

Keywords: Eicosanoids, inflammatory bowel disease, metabolomics, metabonomics, mucosal healing, phospholipids