Department of General Surgery, Medical Center of Digestive Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China.
Front Immunol. 2024 Jul 25;15:1405790. doi: 10.3389/fimmu.2024.1405790. eCollection 2024.
Previous observational studies have revealed the strong relationship between fatty acids (FA) and inflammatory bowel disease (IBD). Nonetheless, due to the inherent limitations of retrospective research, the causality between the two has not been clearly established.
Genetic variants associated with the 17 FA indicators were derived from genome-wide association studies. Summary statistics for the discovery cohort and testing cohort for IBD, including ulcerative colitis (UC) and Crohn's disease (CD), were available from IIBDGC and FinnGen, respectively. Bidirectional MR analysis and sensitivity analysis with multiple measures were applied to comprehensively investigate the causal link between FA and IBD.
Combining the results of various MR methods, the validation of testing cohort, and the merging of meta-analysis, we demonstrated that genetically predicted Omega-3 FA levels, Ratio of Omega-3 FA to total FA, Docosahexaenoic acid (DHA) levels, and Ratio of DHA to total FA reduced the risk of IBD, UC, and CD. Meanwhile, multivariate MR suggested that the risk effects of Omega-3 FA and DHA for UC and CD were mainly affected by Saturated FA and Monounsaturated fatty acid (MUFA). Furthermore, although there was the causal association between Ratio of MUFA to total FA as well as Ratio of Polyunsaturated fatty acid (PUFA) to MUFA and CD, sensitivity analysis prompted that the findings were not robust. None of the above results had a reverse causal effect.
This MR investigation provided evidence of causality between diverse FA and IBD. These findings offered new insights into the treatment and prevention of IBD.
先前的观察性研究表明，脂肪酸（FA）与炎症性肠病（IBD）之间存在很强的关联。然而，由于回顾性研究固有的局限性，两者之间的因果关系尚未明确确立。
与 17 种 FA 指标相关的遗传变异来自全基因组关联研究。IBD（包括溃疡性结肠炎（UC）和克罗恩病（CD））的发现队列和测试队列的汇总统计数据可从 IIBDGC 和 FinnGen 获得。双向 MR 分析和使用多种措施的敏感性分析被应用于全面研究 FA 和 IBD 之间的因果关系。
综合各种 MR 方法的结果、测试队列的验证以及荟萃分析的合并，我们表明，遗传预测的 Omega-3 FA 水平、Omega-3 FA 与总 FA 的比值、二十二碳六烯酸（DHA）水平和 DHA 与总 FA 的比值降低了 IBD、UC 和 CD 的风险。同时，多变量 MR 表明，Omega-3 FA 和 DHA 对 UC 和 CD 的风险效应主要受饱和脂肪酸和单不饱和脂肪酸（MUFA）的影响。此外，尽管 MUFA 与总 FA 的比值以及多不饱和脂肪酸（PUFA）与 MUFA 的比值与 CD 之间存在因果关联，但敏感性分析提示这些发现并不稳健。上述结果均没有反向因果关系。
本 MR 研究提供了 FA 与 IBD 之间存在因果关系的证据。这些发现为 IBD 的治疗和预防提供了新的见解。
