Genetic evidence of dietary patterns and diet-derived antioxidants on polyp development through gut microbiota modulation

Previous studies have shown that dietary habits are associated with the development of several diseases in humans. However, whether these factors contribute to polyps remains unknown. In this study, we employ Mendelian randomization (MR) to investigate the causal relationship between genetically predicted dietary factors, including diet-derived antioxidant intake, and 4 types of polyps: nasal polyps, female genital tract polyps, colorectal polyps, and gastric polyps, as well as to explore the mediating role of the gut microbiota. We identified genetic variants associated with 7 dietary sources of circulating antioxidants and 15 dietary intake-related factors using genome-wide association study data from the UK Biobank. Genome-wide association study data for the 4 polyp types were obtained from the FinnGen consortium. Two-sample MR analyses were conducted to identify dietary factors causally associated with polyps, and sensitivity analyses were performed to assess heterogeneity and horizontal pleiotropy. Finally, 2-step MR was used to mine potential intermediary gut microbiota. Significant causal associations were identified between specific dietary components/gut microbiota and polyp risk. A total of 4 causal pathways were identified in which dietary factors modulated gut microbiota and thus polyps. Increased intake of lobster/crab inhibited the proliferation of Holdemania, thereby increasing the risk of nasal polyps. Bread intake, a protective factor for colon polyps, acted by increasing the abundance of Flavonifractor. The intake of bacon inhibits the protective factor Alcaligenaceae in gastric polyps. Coffee intake increased the risk of female genital tract polyps by increasing the abundance of Victivallaceae. Our findings provide evidence of a causal effect of dietary intake and diet-derived antioxidants on polyps in humans, emphasizing the importance of gut microbiota during polypogenesis. Approaches that target these factors may offer bright prospects for the treatment and prevention of polyps.