Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse

Alzheimer’s disease (AD) is the most common form of dementia. Besides its cognitive phenotype, AD leads to crucial changes in gut microbiome composition in model mice and in patients, but the reported data are still highly inconsistent. Therefore, we investigated chronic effects of AD-characteristic neurotoxic amyloid-β (Aβ) peptides as provided by transgenic overexpression (5xFAD mouse model) and acute effects due to oral application of Aβ on gut microbes. Astonishingly, one-time feeding of wild type mice with Aβ(42) provoked immediate changes in gut microbiome composition (β diversity) as compared to controls. Such obvious changes were not observed when comparing 5xFAD mice with wild type littermates. However, acute as well as chronic exposure to Aβ significantly affected the abundance of numerous individual operational taxonomic units. This provides first evidence that acute in vivo exposure to Aβ results in a shift in the enteric microbiome. Furthermore, we suggest that chronic exposure to Aβ might trigger an adaptive response of gut microbiota which could thereby result in dysbiosis in model mice but also in human patients.