Gut Microbiota, Circulating Cytokines and Eosinophilic Esophagitis: A Comprehensive Mendelian Randomization Study

Background : Observational studies have reported the correlation between gut microbiota, cytokines and eosinophilic esophagitis (EoE), but the underlying causal relationship remains largely unclear. Methods : We used the Mendelian randomization approach based on large-scale genome-wide association study datasets to evaluate the causal relationship between gut microbiota and EoE, and to identify whether cytokines play a mediating role. We applied the inverse variance weighted method as the primary analysis followed by several sensitivity analyses. Results : We identified five bacterial taxa at various levels and two cytokines which exerted a positive casual effect on EoE. Eight bacterial taxa and one cytokine were found to have a protective effect on EoE. Cytokines did not act as mediating factors from gut microbiota to EoE. Reversely, EoE altered the composition of microbiome and levels of circulating cytokines. Sensitivity analyses confirmed the robustness of primary results. Conclusions : Gut microbiota and cytokines were causally associated with EoE, and cytokines did not play a mediating role in the pathway from gut microbiota to EoE.