The Effects of Fatty Acids on Inflammatory Bowel Disease: A Two-Sample Mendelian Randomization Study

Abstract

Inflammatory Bowel Disease (IBD) is a severe relapsing inflammation of the gastrointestinal tract. The association between fatty acids (FAs) and IBD is controversial and it remains unclear whether there is a causal relationship between them. Mendelian randomization (MR) analysis was province/state for affiliations from the same country performed to clarify the causality. Eligible single nucleotide polymorphisms were selected as instrumental variables from six Genome-wide association studies, involving 114,999 individuals in UK Biobank. The summary-level data on IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), were obtained from the International Inflammatory Bowel Disease Genetics Consortium with 20,883 and 27,432 individuals involved. The primary inverse variance weighted (IVW) method as well as other supplementary analysis ones were adopted to evaluate the causal relationship between diverse FAs and IBD. The tests for heterogeneity and pleiotropy, and Leave-one-out analysis were adopted to verify the stability of the results. Omega-3 FA was found to have a causal effect on UC instead of CD. For each Standard Deviation increase in Omega-3 FA genetic levels, the risk of ulcerative colitis was found to be reduced by 39.9% by the IVW method (p = 1.766 × 10−4), by 57.8% by the MR Egger (p = 1.11 × 10−2), by 51.5% by the Weighted median estimator (p = 7.706 × 10−4), by 39% by the Maximum likelihood estimation (p = 3.262 × 10−4), and by 54.5% by the penalized weighted median estimator (p = 1.628 × 10−4). No causal relationship was found between other FAs (including total FA, saturated FA, polyunsaturated FA, monounsaturated FA and omega-6 FA) and IBD. The pleiotropic test and Leave-one-out analysis both proved the validity and reliability of these MR analyses. Omega-3 FA was observed to have a protective effect against UC, providing a new perspective on the investigation of the associations between FAs and IBD.

Effect of Lifelong Exposure to Dietary Plant and Marine Sources of n-3 Polyunsaturated Fatty Acids on Morphologic and Gene Expression Biomarkers of Intestinal Health in Early Life

“…The intestinal-health-promoting effects of n -3 PUFA supplementation have been studied in the context of established conditions with compromised intestinal health, such as obesity [ 11 ], obesity-associated colitis [ 46 ], or IBD/experimental colitis studies using long-chain n -3 PUFA from marine/fish oil [ 47 , 48 , 49 , 50 ] or plant/flaxseed oil [ 47 , 51 , 52 , 53 ], with some studies reporting no beneficial effects [ 54 , 55 , 56 ]. Additionally, there is evidence that n -3 PUFA can also promote intestinal healing and restoration of the intestinal epithelial barrier [ 48 , 54 ].…”

Causal relationship between type 1 diabetes mellitus and six high-frequency infectious diseases: A two-sample mendelian randomization study

“…Other MR methods were also performed to guarantee the effectiveness and stability of the outcomes. The maximum likelihood method provides an estimator with the lowest standard error under essentially all conditions compared with other MR methods (30). The penalized weighted median (PWM) estimator is a novel MR method that can provide a consistent estimator when significant heterogeneity exists (31).…”

Prognostic value of blood saturated fatty acids in inflammatory bowel diseases

“…На сьогодні поширеність ЗЗК є найвищою в Європі (322-505 випадків/100 000 осіб), але останніми десятиліттями ця захворюваність зростає у всьому світі. ЗЗК можуть виникати в будь-якому віці з першим піком в 19-25 років та з другим -в більш пізній період життя [1,4].…”

“…Дослідження останніх років розкривають важливу роль ЖК у патофізіології та розвитку ЗЗК [4,9,16]. Так, вченими було показано, що при ХК КЛЖК беруть участь у підтримці кишкового гомеостазу шляхом стабілізації гіпоксія-індукованого фактора (ГІФ); нормалізації кишкового епітеліального бар'єра шляхом модуляції щільних з'єднань; впливу на про-та протизапальні медіатори; пригніченні активності гістондеацетилази; індукції антимікробної активності; тоді як ДЛЖК виступають як попередники про-та протизапальних молекул; беруть участь у регуляції експресії генів, що кодують фактори, залучені у запальний процес; впливають на про-та протизапальні медіатори [9].…”