Background: The association between gut microbes and Alzheimer's disease (AD) has not been entirely elucidated.
Objective: We aimed to demonstrate the association between gut microbes and AD and to further investigate the pathogenesis of microbes with a causal relationship to AD.
Methods: Mendelian randomization analyses were used to determine the significant causal relationship between gut microbes and AD. Protein-protein interaction (PPI) network was used to identify the hub genes. Functional enrichment analysis was used to reveal the pathogenesis theoretically between gut microbes and AD.
Results: In the present study, a total of 32 microbes were identified that were significantly associated with AD. Subsequently, DLGAP2, NRXN3, NEGR1, NTNAP2, MYH9, and SCN3A were identified as hub genes. The genes NRXN3, NEGR1, and NTNAP2 were enriched in the cell adhesion molecules (CAMs) signaling, and the taxons of gut microbes that corresponded to these were Bifidobacterium adolescentis, Actinomycetales, and Intestinimonas massiliensis.
Conclusions: Bifidobacterium adolescentis, Actinomycetales, and Intestinimonas massiliensis may promote the progression of AD through the regulation of the CAMs signaling pathway-mediated synaptic function. Hence, the in-depth study of gut microbes may increase the efficiency of screening and diagnosis of AD.
Keywords: Alzheimer's disease; bioinformatics; cell adhesion molecules signaling; gut microbes; mendelian randomization.
© The Author(s) 2025.