Early-life exposure to APP/PS1 mice increases neuroinflammation through gut microbes

Abstract

Objective

The gut-brain axis has been implicated in the complex pathogenesis of Alzheimer's disease (AD), but the mechanism of action is unclear. This study was performed to clarify the link between the gut microbiota and AD.

Methods

Gut microbiota structure, long-term potentiation (LTP), inflammation levels, AD biomarkers, and metabolomics were monitored. Moreover, the regulatory action of bacterial metabolites on tau protein phosphorylation was evaluated.

Results

Early-life exposure to APP/PS1 mice showed that gut bacteria from donated mice altered the gut microbiota structure in newborn mice, LTP in hippocampal slices was significantly shortened, inflammatory marker levels increased, AD biomarkers were upregulated, and tau protein phosphorylation was significantly higher at multiple sites. Special bacteria, such as Akkermansia, Lactobacillus, and Klebsiella, increased in AD patient samples, which might induce and/or accelerate disease processes.

Conclusion

These results implied that the gut bacteria in AD could change the gut microbiota structure, induce metabolism disorders, induce inflammation and autophagy dysfunction (thus leading to accelerated tau protein phosphorylation), reduce LTP in AD cohoused mouse hippocampus, and increase neuroinflammation. Long-term clinical monitoring is needed to design dietary and nutritional interventions for AD based on the gut microbiota and mycobiota.