MicrobiomeMar 4, 2026

How a person's genes relate to gut bacteria in Alzheimer's disease

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Host genetic variation was linked to an Anaerostipes-enriched gut microbial signature that tracked lower cognitive disability and lower Alzheimer's disease polygenic risk.

Evidence

This multi-omics association study profiled host genotype and gut microbiome in 252 Chinese individuals, then used external cohorts, microbiome GWAS, and gene-function analyses.

Caveat

The study is associative and based on a limited primary cohort, so it does not show that ES-Ana or the 174 associated genes causally protect against Alzheimer's disease.

Simplified

BACKGROUND: Host-microbiome interactions play essential roles in the development of Alzheimer's disease (AD), yet the host genetic impacts on gut microbial alterations in AD remain poorly understood.

RESULTS: Here, we simultaneously profiled host genotype and gut microbiome in 252 Chinese individuals with varying degrees of cognitive disability. Using the latent Dirichlet allocation topic model, we identified the Anaerostipes-enriched enterosignature (ES-Ana) at the microbial subgroup level as significantly negatively associated with cognitive disability, which could be recapitulated in external cohorts. With the whole-genome sequencing data, we performed microbiome genome-wide association studies for the ES-Ana relative abundance. We prioritized 41 lead genetic variants and confirmed that the high ES-Ana relative abundance showed a negative correlation with the polygenic risk score of AD, indicating its protective effect against AD. Furthermore, we identified 174 ES-Ana-associated genes, which are enriched in AD-related biological functions and phenotypes, and exhibite pervasive underexpression in glial cells during brain aging.

CONCLUSIONS: In summary, our study reveals the complex genetic effects on the gut microbiota in AD, and provides novel evidence for the roles of the gut-brain axis in AD. Video Abstract.