The causal association between the new gut microbiota and Alzheimer's disease: A Mendelian randomization study

Background There is a need for more studies to validate the role of gut microbiota in Alzheimer's disease (AD). Objective This study aims to explore the causal association between new gut microbiota and AD using Mendelian randomization. Methods Using genome-wide association study (GWAS) of 473 gut microbiota species and AD in IEU Open GWAS database, independent genetic loci related to gut microbiota were extracted as instrumental variables. The inverse variance weighting method was employed as the main indicator for evaluation. The stability and reliability of the results were further verified by heterogeneity test, outlier detection, horizontal pleiotropy test and leave-one-out analysis. Results Following a thorough screening process, a total of 14 intestinal microbiota were included in the final analyses. The elevated abundance of Agathobacter , Citrobacter A , Clostridium E sporosphaeroides , Eubacterium R , Megamonas funiformis , and Pseudomonas aeruginosa can reduce the risk of AD. Higher abundance of Bifidobacterium , Holdemania massiliensis , Hydrogenophaga , Intestinimonas massiliensis , Megasphaera , Paenibacillus J , Prevotella , and Raoultella could increase the risk of AD. The MR-Egger analyses at 14 “genus” levels showed no horizontal pleiotropy and the p values were all more than 0.05. The leave-one-out analysis showed that results were relatively stable. Conclusions This study revealed a causal relationship between 14 specific gut microbiota and the risk of AD occurrence. Some bacteria are protective, while others increase the risk of AD. These findings are of clinical significance for the treatment and prevention strategies in clinical practice, and it also provides new perspectives for related research on the “gut-brain axis”.