No causal relationship between polyunsaturated fatty acids and inflammatory bowel disease: A Mendelian randomization study

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease, and dietary factors are associated with the onset and progression of IBD. The study aimed to investigate the causal association between some polyunsaturated fatty acids (PUFAs) and IBD, elucidating the nature of interactions occurring between them, and providing complementary guidance for clinical practice. Two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal association between eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), linoleic acid (LA), and arachidonic acid (ARA) and IBD. These PUFAs and IBD were considered the exposure and outcome, respectively. The R TwoSampleMR package was used to conduct the analysis. We employed the weighted median method, weighted mode model, random effects inverse-variance weighted model, and MR-Egger method and observed no causal relationship between EPA, DPA, DHA, ARA, and LA and IBD, Crohn's disease (CD), and ulcerative colitis (UC). Furthermore, in reverse MR analysis, in which IBD, CD, and UC were the exposures and EPA, DPA, DHA, ARA, and LA were the outcomes, we observed no causal effect of IBD, CD, and UC on the investigated PUFAs. Finally, through independent genome-wide association studies, we validated concordant null causal effects of all PUFAs on IBD. Using MR, we systematically assess the causal effects of specific n-3 and n-6 PUFAs on IBD risk. Our results suggest no causal relationship between specific PUFAs (EPA, DPA, DHA, LA, and ARA) and IBD. Therefore, routine PUFA supplementation is unlikely to benefit IBD management and that single-PUFA intervention strategies lack a sound biological basis. Future studies should incorporate ancestry-matched genetic datasets to enhance generalizability, employ multi-omics approaches to investigate PUFAs metabolic pathways, and explore gene-environment interactions in PUFAs metabolism to further elucidate their potential role in IBD pathogenesis.