Causal relationship between gut microbiome and risk of AMD: a two-sample Mendelian Randomization study

Introduction: To identify gut microbiota susceptible to age-related macular degeneration (AMD) development, a Mendelian Randomization (MR) design was employed to systematically screen the gut microbiome for the potential risk of AMD. Methods Instrumental variables of 196 gut microbiota were obtained from a genome-wide association study (GWAS) of the MiBioGen consortium. A Mendelian randomization study was conducted to estimate their effects on AMD risk from R8 FinnGen GWAS (7582 AMD cases and 318039 controls). Inverse variance weighted (IVW) is the primary method to analyze causality, and MR results are verified by several sensitivity analyses. Results IVW results confirmed that Genus-Faecalibacterium (P = 7.56×10 − 4) was correlated with the risk of AMD. Genus-Candidatus_Soleaferrea (P = 2.05×10 − 3) was a protective factor for AMD. Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analysis confirmed the robustness of MR results. Conclusion We confirmed a potential causal relationship between some gut microbiota taxa and AMD, highlighting the association of the "gut-eye" axis and offering new insights into the gut microbiota-mediated mechanism of AMD.