Accelerating action of Alzheimer’s disease gut microbiota on Tau protein hyperphosphorylation: crosstalk of inflammation and autophagy

Abstract Background: The gut-brain axis has been implicated in the complex pathogenesis of Alzheimer’s disease (AD), but the action is unclear, this study was performed to clarify the effect of ad-related gut microbiota on the pathogenesis of AD during pregnancy and early exposure. Methods: A pilot study of gut microbiota in AD patients was performed.Gut microbiota structure, long-term potentiation (LTP), inflammation levels, AD biomarkers, and metabolomics of serum and fecal were monitored after cohousing by cohousing in early life (from pregnancy 14 days to birth 14 days with 8-month old APP/PS1 mice).The regulatory action of bacterial metabolites on Tau protein phosphorylation was evaluated. Results: Gut microbiota from APP/SP1 mice altered structure of gut microbiota in newborn mice, LTP in hippocampal slices was significantly shortened, and inflammatory markers levels were increased, AD biomarkers were upregulated, with significantly higher Tau protein phosphorylation at multiple sites (p < 0.05). Conclusions: These results imply ad-related gut microbiota can change the structure of gut microbiota during pregnancy and early exposure. Changing the structure of gut microbiota in the newborn mice can induce leucine metabolism disorder, induce mTOR mediated autophagy dysfunction and increase the level of inflammation, thus leading to accelerate Tau protein phosphorylation and reduce LTP occurs in AD-cohousing mouse hippocampus.