The Gut Microbiome Alterations and Inflammation-driven Pathogenesis of Alzheimer's Disease

Abstract

Recent scientific discoveries underscore the vital role of the gut microbiota in bidirectional communication with the brain, suggesting that the human gut microbiota may serve as a “second brain” with implications for neurodegenerative disorders like Alzheimer’s Disease (AD). Although human-associated microbial communities are generally stable, common activities, such as antibiotics and high-fat diets, can disrupt them persistently. These enteric bacteria, encompassing commensal and pathogenic microorganisms, significantly influence immune function, brain development, and behavior. They can produce neurotransmitters, neuromodulators, and amyloids. Brain damage mechanisms leading to dementia and AD start with dysbiosis in the intestinal microbiome, causing local and systemic inflammation and disrupting the gut-brain axis. This heightened gut permeability allows various bacteria, viruses, and their neuroactive products, like toxic proteins and inflammatory molecules, to invade. The inflammatory-infectious hypothesis of AD, emphasizing the role of the gut microbiome, gains traction over the longstanding amyloid cascade hypothesis. In conclusion, AD’s origin in the gut and its close link to gut microbiota imbalance present a promising avenue for therapeutic intervention. Modulating gut microbiota through personalized diets or beneficial microbiota interventions to alter microbial partners and their products, including amyloid protein, may emerge as a novel AD treatment.