Interactive association between gut microbiota and thyroid cancer: a Mendelian randomization and systematic review

Context The association between gut microbiota and thyroid cancer remains controversial. Objective We aimed to systematically investigate the interactive causal relationships between the abundance and metabolism pathways of gut microbiota, and thyroid cancer. Methods We leveraged the genome wide association studies for the abundance of 211 microbiota taxa from the MiBioGen study (N=18,340); 205 microbiota metabolism pathways from the Dutch Microbiome Project (N=7738); and thyroid cancer from the largest meta-analysis of Global Biobank Meta-analysis Initiative (N cases=6699 and N participants=1,620,354). We performed a bidirectional Mendelian randomization (MR) to investigate the causality from microbiota taxa, metabolism pathways to thyroid cancer, and vice versa. We did a systematic review of the previous observational studies and compared MR results with observational findings. Results Eight taxa and twelve metabolism pathways had causal effects on thyroid cancer, where RuminococcaceaeUCG004 genus ( P =0.001), Streptococcaceae family ( P =0.016), Olsenella genus ( P =0.029), ketogluconate metabolism pathway ( P =0.003), pentose phosphate pathway ( P =0.016), and L-arginine degradation II in AST pathway ( P =0.0007) were supported by sensitivity analyses. Conversely, thyroid cancer had causal effects on three taxa and two metabolism pathways, where Holdemanella genus ( P =0.015) was supported by sensitivity analyses. The Proteobacteria phylum, Streptococcaceae family, Ruminococcus2 genus, and Holdemanella genus were significantly associated with thyroid cancer in both systematic review and MR, while other 121 significant taxa in observational results were not supported by MR. Discussions These findings implicated the potential role of host-microbiota crosstalk in thyroid cancer, while the discrepancy among observational studies called for further investigations.