Gut microbiota mediating the effect of chronic kidney disease on cognitive dysfunction: a mendelian randomization study

Abstract

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. 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 intricate relationship between renal function markers—particularly creatinine, which paradoxically correlates positively 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.