Ketogenic Diet Modulates Gut Microbiota-Brain Metabolite Axis in a Sex- and Genotype-Specific Manner in APOE4 Mice.

ABSTRACT: The apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), associated with early brain metabolic dysfunction and gut microbiome alterations. Targeting these early changes through dietary interventions may reduce AD risk in asymptomatic carriers. This study evaluated whether a ketogenic diet (KD) could reshape the gut microbiome and enhance key brain metabolite levels in young APOE4 mice, using APOE3 mice as a neutral-risk comparison. Male and female APOE3 and APOE4 mice were fed either a control diet or KD for 16 weeks, starting at 12 weeks of age. We used shotgun metagenomics and targeted brain metabolomics to identify microbe-metabolite signatures linked to neuroprotection. KD increased beneficial species such as Lactobacillus johns

SUBMITTER: Ivanich K 

PROVIDER: S-EPMC12870807 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature