Evaluating Causal Effects of Gut Microbiome on Alzheimer’s Disease

Background: The preceding evidence indicates a close correlation between imbalances in the gut microbiome and Alzheimer’s disease (AD), yet the direct causal relationship remains unclear. Our objective is to investigate this potential causal connection. Methods: We obtained summary results from two significant genome-wide association studies (GWAS) on gut microbiota (the MibioGen consortium and the Dutch Microbiome Project), along with one GWAS summary result for AD. Using a two-sample Mendelian randomization (TSMR) analysis, we examined the potential causal effects of gut microbiota on AD. Results: Our TSMR analysis revealed that 16 gut bacterial taxa were linked to a reduced risk of AD. These included phylum Tenericutes, classes Bacilli and Clostridia along with its order Clostridiales, family Bacteroidaceae, genus Bacteroides, and species Bifidobacterium bifidum (OR: 0.867∼0.971, P ≤ 0.045). Conversely, the presence of 12 taxa correlated with an increased risk of AD. These comprised class Actinobacteria and its family Coriobacteriaceae, as well as class Betaproteobacteria, its order Burkholderiales, and its family Sutterellaceae (OR: 1.042∼1.140, P ≤ 0.035). Conclusion: Our research uncovered evidence suggesting certain gut bacterial species might play a causal role in AD risk, providing a fresh angle for AD treatment strategies.