Exploring the Relationship Between Sporadic Creutzfeldt-Jakob Disease and Gut Microbiota Through a Mendelian Randomization Study.

ABSTRACT

Observational studies have shown gut microbiota changes in sporadic Creutzfeldt-Jakob disease patients, but the causal relationship remains unknown. We aimed to determine any causal links between gut microbiota and this prion disease. Using Mendelian randomization analysis, we examined the causal relationship between gut microbiota composition and sporadic Creutzfeldt-Jakob disease. Data on gut microbiota (N = 18,340) and disease cases (5208) were obtained. Various analysis methods were used, including inverse variance weighted, Mendelian randomization-Egger, weighted median, simple mode, and weighted mode. In addition, MR-PRESSO was used to evaluate horizontal pleiotropy and detect outliers. Pleiotropy and heterogeneity were assessed, and reverse analysis was conducted. Negative associations were found between sporadic Creutzfeldt-Jakob disease and family Defluviitaleaceae, family Ruminococcaceae, genus Butyricicoccus, genus Desulfovibrio, and genus Eubacterium nodatum. Genus Lachnospiraceae UCG010 showed a positive correlation. Reverse analysis indicated genetic associations between the disease and decreased levels of family Peptococcaceae, genus Faecalibacterium, and genus Phascolarctobacterium, as well as increased levels of genus Butyrivibrio. No pleiotropy, heterogeneity, outliers, or weak instrument bias were observed. This study revealed bidirectional causal effects between specific gut microbiota components and sporadic Creutzfeldt-Jakob disease. Certain components demonstrated inhibitory effects on disease pathogenesis, while others were positively associated with the disease. Modulating gut microbiota may provide new insights into prion disease therapies. Further research is needed to clarify mechanisms and explore treatments for sporadic Creutzfeldt-Jakob disease.