Disease-specific alterations in plasma fatty acids and arachidonic acid metabolites in ulcerative colitis and crohn’s disease

Abstract Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are characterized by chronic intestinal inflammation and significant clinical variability. Growing evidence suggests that disruptions in systemic lipid metabolism play a role in IBD pathophysiology; however, detailed analysis of circulating fatty acids and arachidonic acid–derived lipid mediators in UC and CD remains limited. Therefore, in this cross-sectional observational study, we measured plasma fatty acids and arachidonic acid–derived oxylipins in patients with UC, patients with CD, and healthy controls. The study analysed 46 patients with UC and 16 with CD, for a total of 62 patients with IBD (UC + CD). These patients were compared to 40 healthy controls. Plasma fatty acids and arachidonic acid–derived oxylipins were measured using targeted high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC–QTOF–MS). Associations with disease phenotype, sex, disease activity, and pharmacological treatment were analyzed. Both UC and CD showed a global reduction in circulating medium- and long-chain fatty acids compared to controls. Plasma arachidonic acid levels were significantly lower in both diseases, with a more notable reduction in CD. UC was characterized by a selective loss of arachidonic acid epoxide metabolites, while CD exhibited increased levels of alternative arachidonic acid–derived metabolites, with some sex-specific differences. Most lipid changes were not significantly associated with traditional inflammatory markers or disease activity. In exploratory subgroup comparisons, some CD patients receiving biological therapy or corticosteroids exhibited selected fatty acid levels closer to those observed in healthy controls. IBD is linked to disease-specific disruptions in systemic fatty acid profiles and arachidonic acid metabolism. Distinct patterns of lipid alterations were observed in UC and CD, highlighting lipid metabolism as an additional aspect of IBD pathophysiology. These exploratory findings may help identify candidate lipid markers for evaluation in larger, independently validated studies.