Investigating the uncertain causal link between gut microbiota and glaucoma: A genetic correlation and Mendelian randomisation study

Abstract Background Glaucoma is the most common cause of irreversible blindness, and gut microbiota (GM) is associated with glaucoma. Whether this association represents a causal role remains unknown. This study aims to assess the potential association and causal link between GM and various forms of glaucoma, emphasising the need for cautious interpretation of the strength of these associations. Methods Employing a two‐sample bidirectional Mendelian randomisation (MR) framework with false discovery rate correction and various sensitivity analyses, supplemented by genetic correlation analysis via linkage disequilibrium score regression (LDSC) and colocalisation for European summary‐level data between MiBioGen consortium and FinnGen Study, we sought to explore the relationship between GM and glaucoma. Results While certain microbial taxa showed potential associations with glaucoma subtypes (e.g., Erysipelotrichaceae with primary angle closure glaucoma, Senegalimassilia with exfoliation glaucoma), the overall findings suggest a complex and not definitively causal relationship between GM and glaucoma. Notably, reverse MR analysis did not establish a significant causal effect of glaucoma on GM composition, and no consistent genetic correlations were observed between GM and glaucoma. Conclusions While our study provides some evidence of associations between specific GM taxa and glaucoma, the results underscore the complexity of these relationships and the need for further research to clarify the potential causal links. The findings highlight the importance of interpreting the gut‐eye axis with caution and suggest that while GM may play a role in glaucoma, it is unlikely to be a predominant causal factor.