Dissecting the Influence of the Gut Microbiota on the Brain in AD
The major goal of this project is to identify microbes and metabolites that affect brain aging and to understand how microbes program cells in the brain towards dysfunction and Alzheimer’s disease. In the brain, there are 4 major cell types, neurons, microglia, astrocytes, and oligodendrocytes, which can be affected by the gut microbiota. In Aim 1, we will investigate whether bacteria in the gut can affect the programming of these 4 cell types in the brain to switch them from a healthy to a dysfunctional state. In Aim 2, we will search for microbial metabolites that may affect cells in the brain in the hopes of uncovering novel therapeutics to protect the brain in aging and in Alzheimer’s disease.
Little is known about why neurons, microglia, astrocytes, and oligodendrocytes in the brain become dysfunctional in Alzheimer’s disease, but our new studies suggest that the gut microbiota may be a contributing source for this dysfunction. An innovative aspect of this project is that we will investigate how the gut microbiota affect genes that can program cells in the brain towards health or disease. Another innovative aspect is the investigation of bacterial metabolites on epigenetic programming, which may be important bacterial signals to the brain in AD. Our project may increase our understanding of how the gut microbiota controls brain function in AD. Identification of bacterial metabolites that have a beneficial effect on maintaining cellular function in aging and AD provides a clear path forward for the development of novel strategies to prevent and treat AD.