Genetic prediction of the effect of gut microbiota on retinal vein occlusion via blood metabolites.

PURPOSE: Given the unclear causal relationship between gut microbiota (GM) and retinal vein occlusion (RVO) and the potential mediating role of blood metabolites, this study aims to investigate this causal link and the mediating effects of blood metabolites.

METHODS

Our Mendelian randomization (MR) study used data from genome-wide association studies pooled data, including 473 microbiota taxa (n = 5959), 233 blood metabolites (n = 136,016), and RVO cases and controls from the FinnGen consortium (cases, n = 775; controls, n = 308,633). We used bidirectional two-sample MR, multivariate MR, and mediation analysis to assess the causal association between GM and RVO.

RESULTS

By analyzing gut microbial metagenomic data with adjustment for confounding factors, we identified 1 taxon with significant causal association and 14 taxa with potential causal links to RVO, where Halomonadaceae remained after Bonferroni correction. Parallel analysis of blood metabolites revealed 18 causal associations (2 significant, 16 potential), with apolipoprotein A-I and creatinine retaining significance post-correction. Three GM taxa affected RVO through three blood metabolites. Caloranaerobacteraceae, Rhodococcus, and Citrobacter A affected RVO through Total cholesterol in HDL2, Apolipoprotein A-I, and phenylalanine, respectively. Apolipoprotein A-1 possessed the greatest mediated effect (5.6%) between Rhodococcus and RVO.

CONCLUSION

These findings provide new insights into the pathogenesis of RVO and may contribute to the development of new strategies for preventing the onset of RVO.