Plant-Based Food Preferences Rich in Polyphenols and Their Causal Effects on Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), represents a major non-communicable chronic disease with increasing global prevalence. Dietary polyphenols from plant-based foods have demonstrated potent anti-inflammatory, antioxidant, and immunomodulatory properties that may play a crucial role in preventing and managing chronic inflammatory conditions. While dietary modifications are frequently advocated in the management of IBD, the intrinsic role of dietary preferences for polyphenol-rich plant foods remains insufficiently understood. By exploring these links, researchers can develop targeted dietary plans that offer new ways to prevent IBD onset and improve treatment outcomes. This study utilized genome-wide association study (GWAS) summary statistics pertaining to 65 plant-based food preferences (sample size ranging from 115,868 to 159,579) and two subtypes of IBD from the most recent FinnGen database (Release 11): UC (n = 438,538) and CD (n = 434,250). The principal causal inference was performed using inverse variance weighted (IVW) in the two-sample Mendelian randomization (MR), with additional analyses conducted using MR-Egger and weighted median methods. To ensure robustness, we conducted extensive sensitivity analyses, incorporating Cochran's Q test, the MR-Egger intercept test, the MR-PRESSO test, and leave-one-out analysis. The directionality of the identified associations was confirmed through Steiger filtering. Additionally, we utilized multivariable Mendelian randomization (MVMR) to evaluate the direct effects of dietary factors on IBD. Colocalization analysis was also employed to identify shared genetic architecture between preferences for polyphenol-rich edible plants and both UC and CD. Following the application of the Bonferroni correction, this MR analysis identified significant genetic associations between preferences for polyphenol-rich plant foods and IBD risk. For CD, preferences for orange juice (rich in flavonoids such as hesperidin and naringin, OR: 0.329, 95% CI: 0.146-0.743, p = 0.007) and lentils/beans (abundant in polyphenols and flavonoids, OR: 0.178, 95% CI: 0.048-0.658, p = 0.010) demonstrated strong protective effects. Using MVMR techniques, we found that UC risk increased among those with aniseed preferences (OR: 3.942, 95% CI: 1.075-14.451, p = 0.039), while individuals who favored melon (rich in cucurbitacins and antioxidants, OR: 0.168, 95% CI: 0.031-0.910, p = 0.039) showed decreased likelihood of developing CD. Through colocalization analysis, we identified shared genetic signals between UC and aniseed preference (PP.H4 = 99.52%), supporting their biological connection. These findings suggest that the anti-inflammatory and antioxidant properties of dietary polyphenols may mediate protective effects through modulation of gut microbiota, enhancement of intestinal barrier function, and regulation of immune responses. Our study provides robust genetic evidence for causal relationships between preferences for polyphenol-rich plant foods and IBD risk, highlighting the potential role of dietary polyphenols in preventing non-communicable chronic inflammatory diseases. These biological insights suggest new directions for improving disease screening and developing targeted dietary interventions for IBD prevention and management.