The impact of the intestinal microbiome on microglial inflammation

Abstract

Background Alzheimer’s disease (AD) is a devastating neurodegenerative disorder associated with aging. While genetics have been shown to be important in the development of AD, environmental and lifestyle factors contribute significantly to the development and progression of AD. It is proposed that microglial inflammation leads to neuronal dysfunction in the brain and may be a driving factor promoting the development of AD. Although microglial inflammation increases with age, there are a number of lifestyle factors that can promote and/or ameliorate microglial dysfunction. These lifestyle factors include established modulators of the intestinal microbiota community structure and function, one of which is alcohol. Chronic alcohol consumption is associated with a greater risk of all types of dementia, especially vascular dementia and AD. Recently, alcohol has been found to promote AD progression in both animal and human studies. We propose alcohol influences microglial inflammation and dysfunction via a mechanism including secreted bacterial products. The objective of this study is to investigate the ability of bacterial‐derived products to influence microglial gene expression and inflammation. Specifically, we investigated the ability of bacterial products to influence alcohol‐induced microglial activation. Method In this study, microglia with and without alcohol exposure will be treated with supernatant from bacteria that are known to be altered following alcohol consumption or shown to be beneficial in blunting inflammation. Microglia will be analyzed for NLRP3 inflammasome activation and IL‐1 production. Result The results of this study demonstrate that secreted bacterial products modulate alcohol‐induced microglia activation including NLRP3 and IL‐1. Conclusion The proposed research is significant because it suggests that bacteria found in the mammalian intestine can influence microglia in the brain and therefore may critically influence neurodegenerative disease such as AD. Identification of the intestinal microbiota as a factor that promotes microglial inflammation and dysfunction will lay the groundwork for the development of therapeutic approaches that target the microbiota (i.e., consumption of prebiotics or probiotics) to prevent and treat age‐associated diseases, such as AD.