Role of Circulating Immune Cells in Mediating the Effect of Gut Microbiota on Central Serous Chorioretinopathy: A Mendelian Randomization and Mediation Analysis.
PURPOSE Recent observational studies have revealed gut microbiota influences the development and progression of several retinal diseases. However, the causal relationship between gut microbiota and central serous chorioretinopathy (CSCR) are still not understood. METHODS The data of gut microbiota and circulating immune cell traits were identifed from large‑scale genome‑wide association studies (GWAS) summary data, and the data of CSCR come from FinnGen database.Mendelian randomization (MR) was used to investigate the causal relationships between gut microbiota, circulating immune cells, and CSCR. Mendelian randomization methods included inverse variance weighting and Bayesian weighting. Cochran's Q, Egger intercept, and MR-PRESSO were used to evaluate heterogeneity, genetic pleiotropy, and horizontal pleiotropy. Sensitivity was evaluated using leave-one-out method.Finally, we explored whether immune cell act as a mediating factor in the pathway from gut microbiota to CSCR. RESULTS 12 gut microbiota traits were associated with increased genetic risk of CSCR, 2 were associated with decreased genetic risk of CSCR.Mediated mendelian randomization analysis identified 10 pathways through which gut microbiota affects the genetic prediction of CSCR through circulating immune cell mediation, with Demequinaceae via IgD-CD24-% lymphocyte (7.0%) and CD24 on sw mem (3.5%), Demequina via IgD-CD24-% lymphocyte (9.6%), GCA-900066575 sp900066385 via CD4 on CD28 + CD4+ (9.7%), Saccharofermentanaceae via CD45 on HLA DR+T cells (4.7%), CD80 on plasmacytoid DC (5.0%), and CD80 on CD62L + plasmacytoid DC (5.9%), UBA737 via HLA DR+CD8br AC (4.3%), CAG-1000 sp000434555 via Resting Treg% CD4 Treg (3.3%) affecting the genetic risk of CSCR. CONCLUSIONS Our mediated mendelian randomization analysis provides genetic evidence suggesting that circulating immune cells may mediate the causal relationship between gut microbiota and CSCR. The identified associations and mediation effects offer new insights into potential therapeutic avenues for CSCR.