Impact of Alcohol Induced Intestinal Microbiota Dysbiosis in a Rodent Model of Alzheimers Disease. mouse gut metagenome

This project investigates the relationship between alcohol consumption and brain neurodegeneration in an Alzheimers Disease transgenic mouse model. Alzheimers disease is a devastating neurodegenerative disorder associated with aging. While genetics is important in the development of Alzheimers disease, environment and lifestyle contribute significantly to the development and progression of Alzheimers disease. One such lifestyle factor is alcohol consumption. Chronic alcohol consumption is associated with a greater risk of all types of dementia, especially Alzheimers disease. We investigated whether alcohol promotes Alzheimers disease via a mechanism involving proinflammatory alterations to the intestinal microbiota. Alcohol has numerous effects on the body including alterations in the intestinal microbiome and compelling evidence indicates that the intestinal microbiome can impact neuroinflammation as well as brain structure and function. Thus, this project examined whether alcohol can promote Alzheimers disease by a mechanism including intestinal microbiota dysbiosis which leads to microglial activation, neuroinflammation, brain pathology, and cognitive dysfunction. This was done through a 20 week alcohol consumption study in Alzheimers Disease transgenic mice and their respective wild typle control. The study began when mice were 10 weeks of age and continued until mice were 30 weeks of age, for a total duration of 20 weeks. When mice were 30 weeks of age, after 20 weeks of experimental manipulations, alcohol was removed for two weeks prior to initiating behavioral testing, to avoid any potential confounds of alcohol on behavioral performance, following the protocol in the previously published study, followed by tissue harvest at the of study. Stool was collected at two timepoints, the end of treatment, last week of alcohol consumption, and end of study, the night before tissue harvest. This experiment was conducted in both males and females, and each sex was examined separately.