Intermittent infection and gut microbiota in Alzheimer’s Disease
The interplay between gut microbiome dysbiosis and Alzheimer’s Disease (AD) continues to be defined. Individuals with pre-clinical AD have different gut bacteria assemblages. Bacteria species level differences are associated with increased amyloid beta and tau levels. Less understood, is if changes in the gut microbiome are a consequence or cause of changes observed in the brain. This proposal posits that viral infections can be drivers of gut dysbiosis that may contribute to AD. Many common viral infections are known to alter the gut microbiome. It is unknown if diverse viruses impact gut dysbiosis in shared or unique mechanisms. We hypothesize that despite unique anatomical sites of infection, diverse viruses alter the gut microbiota in similar manners. 3xTg-AD mice will be used to determine if intermittent viral infection can drive the gut microbiome towards an “unhealthy” population. Corresponding alterations in blood metabolites will be monitored, focusing on the levels of branched chain and aromatic amino acids. These are neurotransmitters precursors. The changes will be correlated to amyloid beta and tau levels in the brain to determine if gut dysbiosis accelerates accumulation of classical AD hallmarks. A neurotropic virus, respiratory virus and peripheral organ virus will be used in these studies. The goal is to generate rigorous preliminary data for future NIH submissions. This project could potentially revealing novel therapeutic or preventative targets to prevent AD progression or interventions for those suffering from AD.