Bidirectional Causal Relationship Between Gut Microbiota and Thyroid Cancer Genetic Susceptibility: A Two-Sample Mendelian Randomization Study

Background Gut microbiota has been closely associated with the development of various diseases, but its causal relationship with thyroid cancer remains unclear. This study aimed to systematically explore the potential causal relationship between gut microbiota and thyroid cancer genetic susceptibility using a two-sample Mendelian randomization (MR) approach. Methods We utilized gut microbiota genome-wide association study (GWAS) data from the MiBioGen project as exposure factors and thyroid cancer GWAS data as outcomes. A total of 120 bacterial genera were analyzed, with inverse variance weighted (IVW) method as the primary analysis method, complemented by weighted median, weighted mode, and MR-Egger regression methods for sensitivity analysis. Heterogeneity tests, pleiotropy tests, Steiger directionality tests, and MR-PRESSO outlier analyses were also performed. Results Among the 120 gut bacterial genera analyzed, 44 (36.7%) were significantly associated with thyroid cancer risk (FDR < 0.05). Of these, 19 genera were associated with increased thyroid cancer risk, such as Anaerotruncus (β = 1.71, OR = 5.52, P = 2.93×10 ^–20 ) and Bifidobacterium (β = 0.66, OR = 1.94, P = 1.28×10 ^–34 ); while 25 genera were associated with decreased thyroid cancer risk, such as Ruminococcus torques group (β = -1.62, OR = 0.20, P = 6.79×10 ^–19 ) and Ruminiclostridium9 (β = -1.34, OR = 0.26, P = 1.27×10 ^–30 ). Functional enrichment analysis showed that these microbiota mainly participate in biological processes including carbohydrate metabolism, energy production, lipid metabolism, and short-chain fatty acid production. Network analysis further revealed complex interaction patterns among these microbiota. Conclusion This study provides the first MR evidence for a potential causal relationship between gut microbiota and thyroid cancer genetic susceptibility, offering a new perspective for understanding the role of the gut-thyroid axis in thyroid cancer pathogenesis and providing potential targets for the development of prevention and treatment strategies.