Relationship between gut microbiota and Hashimoto’s thyroiditis: a two-sample Mendelian randomization study

Abstract Purpose: Hashimoto's thyroiditis（HT）is one of the most common autoimmune diseases. Observational studies have proved that the gut microbiome is related to the occurrence of HT, but the causal relationship between HT and gut microbiome. However, the causal relationship between gut microbiome and HT remains to be determined. Therefore, the aim of this study is to explore the relationship between HT and gut microbiome. Methods: In this study, bidirectional Mendelian randomization was used to explore the relationship between HT and gut microbiome. GWAS data of gut microbiota were obtained from the MiBioGen database, containing 18340 samples. HT data is from the IEU open GWAS database, which contains 568833 samples. The methods used for MR analysis in this paper include inverse variance weighting (IVW), weighted median, weighted mode, Mr egger, and simple mode. F-statistics and sensitivity analysis were used to measure bias and reliability. SNPs were used as instrumental variables in Mendelian randomization studies. Results: After FDR correction, we found a total of 9 bidirectional causal relationships between gut microbiome and HT. Five of them demonstrated the influence of gut microbiome on HT, respectively are genus Anaerostipes (OR=1.239296,95%CI 1.03378-1.485669, p=0.020389)，family Alcaligenaceae (OR=0.742608, 95%CI 0.61164-0.901619，p=0.002645 )、genus Ruminococcaceae (OR=0.89581, 95%CI 0.810137-0.990542,p=0.03193)、genus Prevotella7 (OR=0.895026,95%CI 0.810775-0.988031,p=0.027898)、phylum Verrucomicrobia (OR=0.838726,95%CI 0.722321-0.973889,p=0.021051 ). Four described the effect of HT on the gut microbiome as follows, phylum Verrucomicrobia (OR=0.968114, 95%CI 0.938525-0.998637,p=0.040743)，class Deltaproteobacteria (OR=0.970233, 95%CI 0.942334-0.998958,p=0.042353)，family Verrucomicrobiaceae (OR=0.963272，95%CI 0.933234-0.994277,p=0.020607)，family Christensenellaceae（OR=1.044625, 95%CI 1.003784-1.087127,p=0.031903). No obvious horizontal pleiotrophy was found by MR-Egger intercept test and MR-PRESSO global test. Conclusions: This Mendelian randomization study revealed the relationship between gut microbiome and autoimmune disease ——HT, which may provide a new direction for the future research on the interaction mechanism between the two, and provide a new reference for the study of risk factors of HT. In turn, we can use the intestinal flora as a biomarker for the early diagnosis of HT.