Rewriting Inflammation in IBD: Lipidomics from Pathogenesis to Clinical Application

Lipids (sphingolipids, fatty acids, phospholipids, and lipoproteins) are vital to intestinal barrier integrity, as precursors for pro-inflammatory and pro-resolving mediators and undergo remodelling through host microbiome interactions. Accumulating evidence implicates the Western diet-high in long-chain saturated and omega-6 polyunsaturated fatty acids and low in omega-3-in both the onset and progression of IBD. In contrast, microbiota derived lipid metabolites, including short-chain fatty acids and secondary bile acids, contribute to mucosal homeostasis and immune regulation. This review is structured around three interconnected pillars. First, we classified lipidomic alterations in IBD across major lipid classes: sphingolipids, fatty acids, phospholipids, and lipoproteins by integrating host, dietary, and microbiome contributions. Second, we examined the potential of lipidomics in IBD as a source of prognostic, diagnostic and therapy response biomarkers. Third, we critically assessed the challenges that currently limit clinical implementation including analytical variability, pre-analytical confounding, small cohort sizes, and the lack of prospective validation. Addressing these barriers will be essential to fully realise the potential of lipidomics in advancing personalised care for patients with IBD.