Multi-omics profiling reveals gut microbiome signatures associated with cognitive decline in Alzheimer's disease
Zhixin Zhao1, Feiyan Zhao1, Mengdi Zhang1,2
1Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia 010018, China.
Abstract:
Alzheimer's disease (AD) is increasingly being linked to gut microbial dysbiosis via the gut-brain axis. We applied integrated metagenomics and metabolomics to characterize gut microecology in 28 patients with AD and 33 controls. Metagenomic analysis revealed distinct microbial community structures, with increased abundance of Akkermansia massiliensis, Alistipes onderdonkii, and Barnesiella intestinihominis in AD. Phageome analysis revealed increased richness and altered composition, with more Podoviridae and fewer Microviridae. Functional profiling identified shifts in microbial metabolic pathways involving tryptophan and short-chain fatty acid metabolism. Untargeted metabolomics revealed elevated fecal spermidine, taurocholate, and glycerophosphocholine levels in patients with AD. A random forest model combining metabolites, gut metabolic modules, and bacteriophages achieved good within-cohort classification (AUC = 0.83) but lacked external validation due to unavailable matched fecal metabolomic data. Overall, these findings link AD to coordinated disruptions across bacterial, viral, and metabolic gut layers, highlighting the need for external validation and mechanistic studies.
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