Causal effects of gut microbiota on IgG levels after Helicobacter pylori (H pylori) infection: Insights from genome-wide Mendelian randomization

Gut microbiota has been reported to influence immune responses and various diseases. However, the causal relationship between specific bacterial taxa and IgG levels following H pylori infection remains unclear. We employed a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary statistics to evaluate the causal effects of gut microbiota composition on IgG levels post-H pylori infection. Robustness was assessed through sensitivity analyses, including MR-Egger, weighted median, and MR-PRESSO tests. Additionally, functional enrichment analysis of significant genes was performed to explore potential biological pathways. Our MR analysis identified 11 microbial taxa significantly associated with IgG levels. Six gut microbial taxa, including Akkermansia and Ruminococcaceae UCG002, exhibit a negative causal association with IgG level changes, exerting beneficial effects. Conversely, 5 taxa such as Parabacteroides and Dialister display a significant positive causal relationship with IgG level alterations, potentially inducing excessive activation or suppression of the immune system and leading to detrimental consequences. Sensitivity analyses confirmed the robustness of these findings with no evidence of pleiotropy or heterogeneity. Functional enrichment analysis highlighted pathways linked to immune regulation, neurotransmitter signaling, and inflammatory responses. This study elucidates the causal relationships between gut microbiota and IgG levels after H pylori infection, offering insights into microbiota-mediated immune modulation and potential targets for therapeutic intervention.