Berberine alleviates Alzheimer's disease by regulating the gut microenvironment, restoring the gut barrier and brain-gut axis balance

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease. Intestinal flora and its metabolism play a significant role in ameliorating central nervous system disorders, including AD, through bidirectional interactions between the gut-brain axis. A naturally occurring alkaloid compound called berberine (BBR) has neuroprotective properties and prevents A beta-induced microglial activation. Additionally, BBR can suppress the synthesis of A beta and decrease BACE1 expression. However, it is still unclear if BBR therapy can alleviate AD by changing the gut flora. Purpose: In this study, we examined whether a partial alleviation of AD could be achieved with BBR treatment and the molecular mechanisms involved. Methods: We did this by analyzing alterations in A beta plaques, neurons, and related neuroinflammation-related markers in the brain and the transcriptome of the mouse brain. The relationship between the intestinal flora of 5xFAD model mice and BBR treatment was investigated using high-throughput sequencing analysis of 16S rRNA from mouse feces. Results: The findings demonstrated that treatment with BBR cleared A beta plaques, alleviated neuroinflammation, and ameliorated spatial memory dysfunction in AD. BBR significantly alleviated intestinal inflammation, decreased intestinal permeability, and could improve intestinal microbiota composition in 5xFAD mice.