Urinary metabolomic changes and microbiotic alterations in presenilin1/2 conditional double knockout mice

Area of Science:

• Neuroscience
• Microbiology
• Metabolomics

Background:

• Alzheimer's disease (AD) treatments are often clinically inefficient due to their single-target approach.
• The microbiome-gut-brain axis is increasingly recognized for its role in AD progression and metabolic alterations.

Purpose of the Study:

• To investigate the relationship between gut microbiota and metabolic changes in Alzheimer's disease progression.
• To analyze longitudinal changes in metabolomic signatures and microbial communities in a mouse model of AD.

Main Methods:

• Collected urinary and fecal samples from presenilin1/2 conditional double knockout (PS cDKO) mice and wild-type (WT) controls at 2 and 6 months of age.
• Utilized gas chromatography-time-of-flight mass spectrometry for urinary metabolomics and 16S rRNA sequencing for microbiota analysis.
• Employed functional prediction and correlation analysis to link microbial changes with host metabolism.

Main Results:

• PS cDKO mice exhibited memory impairment, altered metabolism (reduced xylitol and glycine), and changes in gut microbiome composition at both early and mature ages.
• Disturbed metabolic pathways included amino acid, carbohydrate, and energy metabolism, aligning with predicted gut microbiome functions.
• Specific bacterial taxa (e.g., Lactobacillus) increased, while others (e.g., norank_f_Muribaculaceae) decreased, correlating with altered metabolite levels.

Conclusions:

• Gut microbiota alterations may play a partial role in the urinary metabolomic changes observed in Alzheimer's disease.
• Integrated analysis of gut microbes and host metabolism offers insights into AD pathogenesis.