Causal relationship between Helicobacter pylori infection and autoimmune diseases of the digestive system: evidence from a Mendelian randomization study

Background: The association between Helicobacter pylori (H. pylori) infection and digestive autoimmune diseases remains unclear, with inconsistent findings in previous observational studies. We conducted Mendelian randomization (MR) analysis to systematically explore the causal relationship and delve into the pathogenesis based on gut microbiota. Methods: This study encompassed anti- H. pylori IgG levels and genome-wide association studies (GWAS) for multiple digestive autoimmune diseases, utilizing diverse MR methodologies to assess the causal relationship between H. pylori antibody levels and these diseases. Associations between H. pylori and ulcerative colitis (UC) were examined using genetic variants from MiBioGen associated with 194 gut microbiota traits. Additionally, a series of sensitivity analyses were performed to validate the results of the initial MR analyses. Results: Our study showed a significant association between anti- H. pylori IgG levels and the incidence risk of UC (β=-0.001, P=0.011). No causal associations were observed with the incidence risk of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), celiac disease, and Crohn's disease (CD). Multiple gut microbiota were found to be correlated with H. pylori infection and UC. Particularly noteworthy is the negative correlation between the abundance of the genus.Anaerofilum and H. pylori antibody levels (β=-0.174, P=0.048). Notably, genus.Anaerofilum exhibited a positive genetic correlation with an increased risk of UC (β=0.0014, P=0.0029). Conclusion: MR analysis confirmed a causal association between anti- H. pylori IgG and UC, but not with CD. The genus.Anaerofilum may increase the risk of UC by inhibiting H. pylori infection.