Relationship Between Gut Microbiota and Hashimoto’s Thyroiditis: A Two-Sample Bidirectional Mendelian Randomization Study

Abstract

Background: 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-effect relationship between HT and gut microbiome is not clear. Therefore, the causal-effect relationship between the gut microbiome and HT remains to be determined.

Method: In this study, bidirectional Mendelian randomization (MR) was used to explore the relationship between HT and gut microbiome. Genome wide association studies (GWAS) data of gut microbiota were obtained from the MiBioGen database, containing 18340 samples. HT data were 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. Single Nucleotide Polymorphisms (SNPs) were used as Instrumental Variables (IVs) in MR studies.

Results: After false discovery rate (FDR) correction, we found a total of 9 bidirectional causal-effect relationships between gut microbiome and HT. Five of them demonstrated the influence of gut microbiome on HT, respectively were 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 MR 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.