Dissecting the Genetic Correlations and Causal Effects of Gut Microbiota on Pan-Cancer Phenotype: Driven by Common Dietary Preferences.

Previous studies have found that the gut microbiota are associated with various types of cancer. However, the effects under the pan-cancer phenotype and whether they are driven by dietary preferences remain unclear. Here, we aim to comprehensively examine the genetic correlations and causal effects between gut microbiota and pan-cancer using linkage disequilibrium score (LDSC) regression and Mendelian randomization (MR). In addition, MR was also used to estimate the causal effects of dietary preferences on pan-cancer and gut microbiota. The causal steps approach and two-step MR will be used to construct the mediation network. After Bonferroni correction, we identified three gut microbiota that showed suggestive genetic correlations with pan-cancer. In addition, our evidence suggests that six gut microbiota provide suggestive causal effects for pan-cancer. However, in the evidence for dietary preferences on pan-cancer, we identified four significant effects and 20 suggestive effects. Seven pairs of causal effects were identified in the MR analysis of dietary preferences on gut microbiota. After excluding unrobust effects in the sensitivity analysis, we identified four mediation pathways through the causal steps approach. These findings will help us further understand the role of gut microbiota and dietary preferences in cancer and provide valuable insights into dietary patterns for populations at risk of cancer.