Gut-thyroid axis: investigating the causality between the gut microbiota and autoimmune thyroid disease based on a Mendelian randomization study

Abstract

Introduction: Current studies have identified a close connection between the gut microbiota (GM) and autoimmune thyroid disease (AITD), indicating that the dysregulation of the GM could play a crucial bridging role in AITD. However, the causality between them has not been definitively defined. Material and methods: We utilized the summary statistics of GM from the largest available meta-analysis of genome-wide association studies conducted by the MiBioGen consortium. The data on AITD were derived from the Genome-Wide Association Study (GWAS) database. We investigated the causality between GM and AITD through various analytical methods in a bidirectional Mendelian randomization (MR) analysis. This encompassed methods like inverse variance weighted, MR-Egger, weighted median, weighted mode, and simple mode. Results: Our findings revealed a protective effect of genus Methanobrevibacter [odds ratio (OR) = 0.791, p = 0.044], order Rhodospirillales (OR = 0.775, p = 0.019) on Graves’ disease (GD). However, the family Clostridiales vadin BB60 group (OR = 1.222, p = 0.038), genus Anaerofilum (OR = 1.243, p = 0.038), genus Barnesiella (OR = 1.405, p = 0.021), genus Intestinibacter (OR = 1.777, p = 0.000), and order NB1n (OR = 1.270, p = 0.003) were identified as risk factors for GD. In addition, family Alcaligenaceae (OR = 0.691, p= 0.004), family Rhodospirillaceae (OR = 0.813, p = 0.013), genus Butyrivibrio (OR = 0.877, p = 0.019), genus Prevotella 7 (OR = 0.835, p = 0.026), genus Ruminococcaceae UCG011 (OR = 0.883, p = 0.032), genus Ruminococcaceae UCG013 (OR = 0.797, p = 0.048), and order Lactobacillales (OR = 0.759, p = 0.009) had a protective effect on Hashimoto’s thyroiditis (HT). Genus Intestinimonas (OR = 1.247, p = 0.010) was a risk factor for HT. Based on the findings from the reverse MR analysis, AITD did not exert a significant causal influence on the GM. There waere no observed remarkable instrumental variables of heterogeneity or horizontal pleiotropy. Conclusion: Our study offered evidence of causal relationship between certain GM and AITD using two-sample MR analysis. This may provide novel perspectives on diagnosis and latent therapeutic targets for AITD.