Alzheimer’s disease (AD) is the leading cause of dementia in the Western world and to date no cure nor any preventive strategy are available for this neurodegenerative disorder. Bacterial 16S rRNA sequencing from fecal samples revealed a remarkable shift in the gut microbiota of conventionally-raised AD mice compared to healthy, wild-type mice. Based on these findings, we generated germ-free Alzheimer (GF-AD) mouse model and discovered a drastic reduction of cerebral Aβ amyloid pathology when compared to control AD mice with natural intestinal microbiota. In contrast, fecal transplantation of GF-AD with harvested microbiota from conventionally-raised AD mice dramatically increased cerebral Aβ pathology.Altogether, these results strongly support a microbial involvement in the development of AD and show how gut microbiome modulation can slow down or halt its onset. This paves the road to new indirect diagnostic and therapeutic approaches for AD prevention, based on gut microbiota modulation through probiotic cocktails.Based on these findings, the present proposal aims at designing and optimizing an efficient encapsulation strategy to guarantee the survival and the delivery of probiotic strains in the gut as opposed to standard strategies targeting directly the brain. A successful accomplishment of this goal will also allow to derive AD risk factors and to establish an objective baseline setting for AD diagnosis. Ultimately, the present project will open new horizons in biomedical diagnostics and personalized medicine through the marketing of these technologies and therapeutic concepts.