Abstract
BACKGROUND: Gut microbiota (GM) comprises a vast and diverse community of microorganisms, and recent studies have highlighted the crucial regulatory roles of various GM and their secreted metabolites in pancreatic cancer (PC). However, the causal relationship between GM and PC has yet to be confirmed. METHODS: In the present study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal effect between GM and PC, with genome-wide association study (GWAS) from MiBioGen consortium as an exposure factor and PC GWAS data from FinnGen as an outcome factor. Inverse variance weighted (IVW) was used as the primary method for this study. RESULTS: At the genus level, we observed that Senegalimassilia (OR: 0.635, 95% CI: 0.403-0.998, P = 0.049) exhibited a protective effect against PC, while Odoribacter (OR:1.899, 95%CI:1.157-3.116, P = 0.011), Ruminiclostridium 9(OR:1.976,95%CI:1.128-3.461, P = 0.017), Ruminococcaceae (UCG011)(OR:1.433, 95%CI:1.072-1.916, P = 0.015), and Streptococcus(OR:1.712, 95%CI:1.071-1.736, P = 0.025) were identified as causative factors for PC. Additionally, sensitivity analysis, Cochran's Q test, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger regression indicated no heterogeneity, horizontal pleiotropy, or reverse causality between GM and PC. CONCLUSIONS: Our analysis establishes a causal effect between specific GM and PC, which may provide new insights into the potential pathogenic mechanisms of GM in PC and the assignment of effective therapeutic strategies.