Unveiling the influence of lipidomes on inflammatory bowel disease: a bidirectional mendelian randomization study

Apr 11, 2025BMC gastroenterology

How fats in the body and inflammatory bowel disease may affect each other

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Abstract

Fourteen lipid species are significantly associated with inflammatory bowel disease (IBD).

Phosphatidylcholine and lysophosphatidylcholine are linked to ulcerative colitis (UC), with specific odds ratios indicating their potential impact.
In Crohn's disease (CD), cholesterol ester, diacylglycerol, and lysophosphatidylethanolamine also show significant associations with IBD risk.
No significant associations were found between IBD and 179 other lipid species examined in the reverse analysis.
The study suggests that higher levels of certain lipids may be protective against IBD.

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BACKGROUND: Plasma lipid homeostasis is pivotal in maintaining intestinal health. Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD) as distinct subtypes, manifests unique metabolic signatures. However, the specific roles of lipids in the pathogenesis and therapeutic targeting of IBD remain inadequately explored. This study aims to delineate the genetic influences of plasma lipids on IBD risk.

METHODS: We obtained genome-wide association study (GWAS) summary statistics of and IBD (including UC and CD) from published studies to perform two-sample (MR) analyses. Outliers were removed using radial MR, followed by the application of the inverse-variance weighted (IVW) method to assess causal relationships. Sensitivity analyses were also conducted to validate the robustness of the primary results of the MR analyses. Additionally, reverse MR analyses were performed to evaluate the potential for reverse causality.

RESULTS: The MR analysis identified fourteen lipid species significantly associated with IBD, four with UC, and ten with CD. Phosphatidylcholine (PC; P < 0 .05) and lysophosphatidylcholine (OR = 0.83, P < 0.001) were instrumental in UC, while in CD, alongside these, cholesterol ester (OR = 0.86, P < 0.001), diacylglycerol (OR = 1.21, P = 0.004), and lysophosphatidylethanolamine (OR = 1.30, P < 0.001) also demonstrated causal links. Reverse MR analysis revealed no significant associations between IBDs and 179 lipid species.

CONCLUSION: This bidirectional MR study has uncovered genetic evidence of a causal relationship between lipidome and IBD, identifying potential therapeutic targets for IBD treatment. The findings suggest that elevated partial phosphatidylcholine, lysophosphatidylcholine, and cholesterol ester levels could reduce the risk of IBD, indicating a potential protective role for these lipid molecules. This study also underscores the critical role of lipidome variability in advancing our understanding of IBD's pathogenic processes and in developing targeted therapies.

Key numbers

OR = 0.83

Protective effect of phosphatidylcholine

Odds ratio for lysophosphatidylcholine associated with UC risk

OR = 1.21

Increased risk from diacylglycerol

Odds ratio for diacylglycerol linked to CD risk

14 lipid species

Causal association with IBD

Total number of lipid species significantly associated with IBD

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Unveiling the influence of lipidomes on inflammatory bowel disease: a bidirectional mendelian randomization study

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