Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - AD-gut (Alzheimer Disease - gut connection)

Teaser

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 devastating, neurodegenerative disorder.Bacterial 16S rRNA sequencing from fecal samples revealed a remarkable shift in the...

Summary

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 devastating, 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 a 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.

These results strongly point to a microbial involvement in the development of AD and support the hypothesis that a modulation of the gut microbiome may slow down and delay the onset of Alzheimer’s disease. This paves potentially a novel road for AD prevention, based on gut microbiota modulation through well designed probiotic cocktails.

Work performed

Based on these findings, the AD-gut 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.

The core of AD-gut integrates 3 subprojects: encapsulation of probiotics, deciphering the microbiome and understanding induced microbiome alterations due to neurodegenerative disorders. This will reveal the potential of delaying these degenerative diseases by reprogramming the microbiome

Final results

All three pillars are progressing as planned. The first encapsulated probiotics will be ready soon. The reader system for decoding the microbiome is built , ready for the first test runs. The bacteria of interest are partially available in culture. Brain imaging and biochemical control as a readout of the efficacy of administrated probiotics is advancing in parallel, ready in time for a first assessment of the underlying hypothesis: modulating the microbiome may entail a delay of neurodegenerative disorders

Website & more info

More info: http://adgut.eu/.