How is Niacin Production in the Gut Associated with Alzheimer's Disease?

This project aims to study the dysregulation of gut niacin biosynthesis and consequent dysfunction in gut-microglia crosstalk as a novel mechanism underlying Alzheimer’s disease.

Alzheimer’s disease has been correlated with imbalances in gut bacteria; however, the mechanistic link between disease progression and gut dysbiosis has not been fully elucidated. In this project, we will test the hypothesis that the synthesis of niacin in the gut is dysregulated in Alzheimer’s disease, which leads to a reduced supply of niacin to the brain and exacerbates the disease. Conversely, we will assess if increasing niacin synthesis in the gut and supply to the brain can mitigate disease progression, which could pave the way for novel therapeutic strategies aiming at the gut microbiome.

Although there is a clear connection between gut dysbiosis and AD progression, the mechanistic basis for this association is not fully elucidated. This application aims to study the dysregulation of gut niacin biosynthesis and subsequent dysfunction in gut-microglia crosstalk as a novel mechanism underlying AD, which will allow us to further understand the underpinnings of disease progression and pave the way for innovative therapeutic avenues focused on gut microbiome enzymes.

If our hypothesis is confirmed, our study will identify a potential novel therapeutic target for AD, which can be easily accessed with different types of therapeutic strategies, such as chemical compounds or genetically-engineered probiotics. Furthermore, it opens up the study for a new cross-talk avenue between the gut and the brain in AD and perhaps other neurodegenerative diseases.