Gut microbiome mediates the causal relationship between chronic kidney disease and cognitive dysfunction: a mendelian randomization study.

BACKGROUND

The relationship between chronic kidney disease (CKD) and cognitive dysfunction is still debated, and the mechanisms underlying cognitive dysfunction caused by CKD are still not fully understood.

METHODS

This study aimed to explore the potential genetic causality between CKD and cognitive dysfunction using two-sample Mendelian randomization. Furthermore, mediated Mendelian randomization was used to investigate potential genetic mechanisms. A total of 15 genome-wide association study (GWAS) datasets were utilized: six for CKD-related traits (N ≈ 25,000-383,000), eight for cognitive traits (N ≈ 50,000-460,000) from the IEU OpenGWAS database, and one for gut microbiota from the MiBioGen consortium (N = 18,340).

RESULTS

Our study utilizes a two-step Mendelian randomization approach to establish a causal link between chronic kidney disease and cognitive dysfunction, with the gut microbiome playing a pivotal mediating role. The study underscores the complex relationship between renal function markers-particularly creatinine, which shows a positive correlation with cognitive performance-and cognitive health, while also pointing to the modifiable nature of specific gut microbes, such as the Eubacterium fissicatena group, as potential influencers of cognitive decline. Additionally, methanogens' presence in diseases and their dual role in inflammation suggest a complex impact on health that warrants deeper investigation.

CONCLUSIONS

The study found a causal link between CKD and cognitive dysfunction, with the gut microbiome acting as a mediator.