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

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.

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.

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.

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.