Investigating the Joint Effects of Fecal Microbiota Transplant and Diet on Cognitive Function in Alzheimer’s Symptoms in Mice (Mus musculus): A Research Protocol

Abstract

Introduction: Alzheimer’s disease (AD) is characterized by the buildup of amyloid beta (Aβ) protein in the hippocampal and temporal regions, causing progressive cognitive and memory decline. Emerging evidence suggests the gut-brain axis influences AD pathophysiology through gut dysbiosis. This protocol aims to investigate how dietary pattern variations of fecal donors improve cognitive deficits caused by Alzheimer’s Disease, using fecal microbiota transplants (FMT) as the delivery system.

Methods: Thirty healthy donor mice (wild-type 2 months old) will be fed from one of three diets: an "Standard" diet with standard lab nutrition, a "Moderate-fat" diet with moderate fat and sodium, and a "High-fat" diet with high fat and sodium. After 16 weeks of diet pattern variation, fecal microbiota from each diet group will be transplanted into 30 6-month old 5xFAD model mice via oral gavage. Novel object recognition tests will assess long-term memory. Magnetic Resonance Imaging (MRI) will visualize amyloid-beta plaque deposition in the hippocampus. Gut microbiome composition analysis of donor and recipient mice will be achieved via 16S rRNA sequencing.

Anticipated Results: In the “Standard” diet group, limited composition change is expected, as the mice will have consumed this diet prior to testing. Improved cognitive ability is hypothesized. The “Moderate-fat” diet group may experience some microbe composition change. The “High-fat” diet group will exhibit significant microbiome changes, specifically, higher levels of Firmicutes and lower Bacteroidetes. The cognitive decline is expected to deteriorate.

Discussion: If the above results are observed, we would determine if diet helps regulates AD pathology. The study combines diets and FMTs as a long-term treatment for Alzheimer’s, offering insight into the mechanism causing AD pathology.

Conclusion: This study will allow for direct observation of diet-induced dysbiosis on amyloid beta plaques and neurodegeneration, providing insight on the mechanism of Alzheimer’s. Future directions should explore mechanistic effects on lifestyle changes, specifically, diet, and its effect on the gut-brain axis, and should not be translated to humans yet.