Microbiome-targeted strategies for Alzheimer’s disease: multi-omics signatures, mechanistic links, and intervention evidence

Abstract

Alzheimer’s disease (AD) is increasingly studied in relation to gut microbial mechanisms because microbial metabolism, mucosal barrier function, and peripheral immune activation may influence neuroinflammation and host metabolic stress. This review evaluates microbiome-linked evidence in AD with emphasis on studies that combine metagenomics, metabolomics, inflammatory markers, neuroimaging, cerebrospinal fluid or blood biomarkers, and cognitive phenotyping. Current data support several recurring but not yet causal axes, including bile acid transformation, short-chain fatty acid (SCFA) production, trimethylamine N-oxide (TMAO), bacterial product-related inflammatory signaling, and barrier dysfunction. We also review microbiome-targeted interventions, including diet and prebiotics, strain-specified probiotics and synbiotics, oligosaccharide-based agents, gut-restricted antimicrobials, and fecal microbiota transplantation (FMT). The strength of evidence differs substantially across these strategies: sodium oligomannate has been tested in a phase 3 trial, whereas many probiotic, antimicrobial, and FMT approaches remain early clinical, preclinical, or mechanism-generating. Future trials should define a priori microbial, metabolite, immune, and brain biomarker endpoints; control diet, medication, and comorbidity confounding; and validate candidate signatures across independent cohorts before using microbiome profiles for screening or treatment selection.