Longitudinal analysis of the gut microbiome in the 5xfAD mouse model of Alzheimer’s disease

Abstract INTRODUCTION Microbial exposures impact Alzheimer’s disease (AD), and a baseline understanding of AD model microbiomes is vital for improving model efficacy. We describe the evaluation of the microbiome and metabolome in longitudinal samples from the 5xfAD transgenic mouse model. METHODS Cecal and fecal samples from 5xfAD and wild-type B6J (WT) animals from 4– 18 months of age were subjected to DNA extraction and shotgun Illumina sequencing. Metabolomics was performed on plasma and feces from a subset of animals. RESULTS Significant sex, age, and cage-specific differences were observed in the microbiome. Eight bacteria species were elevated in older 5xfAD mice and nine were depleted, including Turicibacter spp. Contradicting published findings covering persons with AD, plasma measurements revealed elevated serotonin in 18 month 5xfAD animals. DISCUSSION Taken together, these findings strengthen the link between Turicibacter abundance and AD and provide a basis for further microbiome studies of murine models for AD.