Association between age-related macular degeneration and the gut microbiota: A two-sample Mendelian randomization analysis

Objective To assess any potential associations between age-related macular degeneration (AMD) and the gut microbiota. Methods Mendelian randomization (MR) analysis was performed on summary data from genome-wide association studies (GWASs) of the gut microbiota and AMD. The gut microbiota was considered the exposure. Instrumental variables (IVs) were identified from a GWAS involving 7,738 participants. The GWAS for AMD from European cohorts served as the outcome dataset, comprising 8,931 AMD patients and 348,936 controls. The primary analysis employed the inverse-variance weighted (IVW) method, with sensitivity analysis conducted to assess the robustness and reliability of the MR analysis results. Results IVW revealed significant associations between specific microbial families/genera and AMD. Notably, the family Peptococcaceae (OR=1.176, 95% CI 1.012 to 1.366, P=0.004), genus Parasutterella (OR=1.167, 95% CI 1.011 to 1.347, P=0.035), and genus Faecalibacterium (OR=1.247, 95% CI 1.071 to 1.451, P=0.034) demonstrated positive causal associations with AMD, while the class Melainabacteria (OR=0.886, 95% CI 0.789 to 0.995, P=0.041) and family Rikenellaceae (OR=0.844, 95% CI 0.726 to 0.981, P=0.027) showed negative causal associations. Sensitivity analysis did not reveal evidence of reverse causality, pleiotropy, or heterogeneity. Conclusion Utilizing MR, we conducted a comprehensive assessment to investigate the causal effect of 412 gut microbiota species spanning from the phylum to the genus level on AMD. Our study revealed significant positive associations between specific genetic variants related to the family Peptococcaceae , genus Parasutterella , and genus Faecalibacterium and an increased risk of AMD. Our findings provide strong evidence supporting a protective role of certain genetic variants related to the class Melainabacteria and family Rikenellaceae against AMD. These results highlight a potential causal relationship between several gut microbiota taxa and AMD. However, future studies employing MR in larger cohorts and incorporating functional analyses are warranted to elucidate the underlying mechanisms by which genetic variants related to the gut microbiota influence the development of AMD.