Exploring reciprocal causation: bidirectional mendelian randomization study of gut microbiota composition and thyroid cancer

Abstract Background While an association between gut microbiota composition and thyroid cancer (TC) has been observed, the directionality and causality of this relationship remain unclear. Methods We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal effect between gut microbiota composition and TC. Gut microbiota data were derived from a diverse population encompassing various ethnicities ( n = 18,340 samples), while TC data were sourced from an European population ( n = 218,792 samples). Instrumental variables, represented by single nucleotide polymorphisms (SNPs), were employed to assess the causal relationship using multiple MR methods, including inverse-variance weighting (IVW), weighted median, weighted mode, MR-Egger, and simple mode. F-statistics and sensitivity analyses were performed to evaluate the robustness of the findings. Results Our investigation identified a comprehensive set of 2934 instrumental variables significantly linked to gut microbiota composition ( p < 1 × 10 - 5 ). The analysis illuminated notable candidates within the phylum Euryarchaeota, including families Christensenellaceae and Victivallaceae, and genera Methanobrevibacter, Ruminococcus2, and Subdoligranulum, which emerged as potential risk factors for TC. On the other hand, a protective influence against TC was attributed to class Betaproteobacteria, family FamilyXI, and genera Anaerofilum, Odoribacter, and Sutterella, alongside order Burkholderiales. Further enhancing our insights, the integration of 7 instrumental variables from TC data ( p < 1 × 10 - 5 ) disclosed the regulatory potential of one family and five genera. Notably, the genus Coprobacter innocuum group ( p = 0.012, OR = 0.944) exhibited the highest probability of regulation. Our meticulous analyses remained free from significant bias, heterogeneity, or horizontal pleiotropy concerns. Conclusion Through a bidirectional two-sample Mendelian randomization approach, we elucidated a potential bidirectional causal relationship between gut microbiota composition and TC. Specific microbial taxa were associated with an increased risk or conferred protection against TC. These findings advance our understanding of the complex interplay between the gut microbiota and TC pathogenesis, offering new insights into the therapeutic potential of modulating the gut microbiota for managing TC.