Gut microbiome dysbiosis is linked to many neurological disorders including Alzheimer's disease (AD). A major risk factor for AD is polymorphism in the apolipoprotein E () gene, which affects gut microbiome composition. To explore the gut-brain axis in AD, long-lived animal models of naturally developing AD-like pathologies are needed. (degu) exhibit spontaneous AD-like symptoms and mutations, making them suitable for studying the interplay between AD genetic determinants and gut microbiome. We analyzed the association between genotype and gut microbiome in 50 humans and 32 degu using16S rRNA gene amplicon sequencing. Significant associations were found between the degu mutation and gut microbial changes in degu, notably a depletion of and and an enrichment of , mirroring patterns seen in people with AD. The altered taxa were previously suggested to be involved in AD, validating the degu as an unconventional model for studying the AD/microbiome crosstalk.