Use of bidirectional Mendelian randomization to unveil the association of <i>Helicobacter pylori</i> infection and autoimmune thyroid diseases.

Abstract

Previous observational studies found associations between <i>Helicobacter pylori</i> infection and autoimmune thyroid diseases (AITDs), but the causal nature of this association is still uncertain. We investigated the causal effect of six crucial antibodies against <i>H. pylori</i> on AITDs using a bidirectional Mendelian randomization (MR). We found that anti-<i>H. pylori</i> outer membrane protein (OMP) significantly increased the risk of hyperthyroidism and Graves' disease (GD). In addition, our reverse MR analysis indicated that hyperthyroidism could increase the levels of cytotoxin-associated gene A and OMP antibodies. We also observed causal roles of GD on anti-<i>H. pylori</i> OMP. Our analyses indicate the mutual effects of <i>H. pylori</i> infection and AITDs, suggesting the existence of a gut-thyroid axis. These results also provide evidence of the bidirectional causal association between anti-<i>H. pylori</i> OMP with hyperthyroidism and GD, resulting in a vicious circle.