Gut Microbiome is Associated with Thyroid Nodule and Functions

Abstract Background: Thyroid nodule affects nearly half of the adult population. Accumulating evidence suggests that gut microbiota plays an important role in the thyroid disorders and functions, yet the association between gut microbiota capacity and thyroid nodule and function have not been studied comprehensively.Methods: We performed a gut microbiota whole-genome wide association study in 537 thyroid nodule participants and 725 controls from the general Chinese population. Thyroid nodules were with the Thyroid Imaging Reporting and Data System assessment.Results: Participants with the highest grade thyroid nodule had decreased gut microbial species and functional richness compared with controls and thyroid nodule with lower grade. Microbiota composition of the low-grade thyroid nodule was similar to that in controls rather than high-grade thyroid nodule. We found significant alternations of overall microbial functional composition in high-grade thyroid nodule but not the species composition, only a small portion of microbioal species were associated with high-grade thyroid nodule. The high-grade thyroid nodule gut microbiome was characterized by greater amino acid degradation and glycolysis, also with fewer Butyrivibrio and lower butyric acid production. Thyroid functions were positively associated with L-histidine and L-tyrosine related biosynthesis pathways, which are essential components of thyrotropin-releasing hormone and thyroxine, also corelated with broad nutrition metabolism pathways including fatty acids, B family vitamins and nucleotides. High-grade thyroid nodule discrimination models based on the gut microbiome and demography were validated using 294 independent samples and showed stable classification power.Conclusion: Our study comprehensively described the gut microbiome characteristics in thyroid nodule and suggested potiental role of the key gut microbiota-driven functional pathways in thyroid nodule and functions metabolism.