The following is a summary of “Unveiling The Influence Of Lipidomes On Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study,” published in the April 2025 issue of the BMC Gastroenterology by Lei et al.

The maintenance of plasma lipid equilibrium is essential for gastrointestinal homeostasis. Inflammatory bowel disease, comprising ulcerative colitis and Crohn’s disease, is characterized by complex immunometabolic dysregulation. Although emerging evidence suggests distinct metabolic alterations in IBD, the precise contribution of specific lipid species to disease susceptibility and progression remains insufficiently understood. This study investigates the causal relationship between plasma lipid profiles and the risk of IBD, UC, and CD using a genetic epidemiology approach.

To assess the potential causal effects of circulating lipids on IBD, researchers conducted a two-sample Mendelian randomization analysis using genome-wide association study (GWAS) summary statistics for 179 lipid species and for IBD and its subtypes, UC and CD. Instrumental variables were selected based on established genetic variants associated with lipid traits. Radial MR was employed to detect and exclude statistical outliers, followed by inverse-variance weighted (IVW) MR as the primary analytic method. Sensitivity analyses, including MR-Egger regression and weighted median approaches, were performed to ensure robustness. Reverse MR analysis was conducted to evaluate the potential for reverse causality between IBD phenotypes and lipidomic traits.

The MR analysis revealed significant causal associations between several lipid species and IBD outcomes. Fourteen lipid species were found to be significantly linked to overall IBD risk, with four specifically associated with UC and ten with CD. Notably, higher genetically predicted levels of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) were inversely associated with UC risk, with LPC demonstrating a strong protective association ([OR] = 0.83, P < 0.001). In CD, additional lipid species exhibited significant associations, including cholesterol ester (OR = 0.86, P < 0.001), which was inversely related to disease risk, and diacylglycerol (OR = 1.21, P = 0.004) and lysophosphatidylethanolamine (OR = 1.30, P < 0.001), which were associated with increased risk. The reverse MR analyses did not identify any significant causal effects of IBD on lipidomic profiles, supporting a unidirectional influence of lipids on disease risk.

This bidirectional MR study provides robust genetic evidence supporting a causal role for specific plasma lipids in the development of IBD. The findings highlight phosphatidylcholine, lysophosphatidylcholine, and cholesterol esters as potentially protective lipid species, offering novel insights into lipid-mediated mechanisms in IBD pathogenesis. These results suggest that lipidomic profiling could inform risk stratification and serve as a foundation for developing lipid-targeted therapies for both UC and CD.

Source: bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-025-03858-3