Cerebral glucose homeostasis deregulation has a role in the pathogenesis and the progression of Alzheimer's disease (AD). Current therapies delay symptoms without definitively curing AD. We have previously shown that probiotics counteract AD progression in 3xTg-AD mice modifying gut microbiota and inducing energy metabolism and glycolysis-gluconeogenesis. Ameliorated cognition is based on higher neuroprotective gut hormones concentrations, reduced amyloid-β burden, and restored proteolytic pathways. Here, we demonstrate that probiotics oral administration improves glucose uptake in 3xTg-AD mice by restoring the brain expression levels of key glucose transporters (GLUT3, GLUT1) and insulin-like growth factor receptor β, in accordance with the diminished phosphorylation of adenosine monophosphate-activated protein kinase and protein-kinase B (Akt). In parallel, phosphorylated tau aggregates decrease in treated mice. Probiotics counteract the time-dependent increase of glycated hemoglobin and the accumulation of advanced glycation end products in AD mice, consistently with memory improvement. Collectively, our data elucidate the mechanism through which gut microbiota manipulation ameliorates impaired glucose metabolism in AD, finally delaying the disease progression.

中文翻译：

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通过口服益生菌操纵肠道微生物群可恢复阿尔茨海默病小鼠模型的葡萄糖稳态

脑葡萄糖稳态失调在阿尔茨海默病 (AD) 的发病机制和进展中发挥作用。目前的疗法延迟了症状，而不能彻底治愈 AD。我们之前已经表明，益生菌可以抵消 3xTg-AD 小鼠的 AD 进展，从而改变肠道微生物群并诱导能量代谢和糖酵解-糖异生。改善的认知基于更高的神经保护性肠道激素浓度、减少的淀粉样蛋白 β 负担和恢复的蛋白水解途径。在这里，我们证明口服益生菌通过恢复关键葡萄糖转运蛋白（GLUT3、GLUT1）和胰岛素样生长因子受体 β 的大脑表达水平来改善 3xTg-AD 小鼠的葡萄糖摄取，与磷酸腺苷活化蛋白激酶和蛋白激酶 B (Akt) 的磷酸化减少一致。同时，磷酸化的 tau 聚集体在治疗的小鼠中减少。益生菌可以抵消 AD 小鼠糖化血红蛋白的时间依赖性增加和晚期糖化终产物的积累，并始终如一地改善记忆力。总的来说，我们的数据阐明了肠道微生物群操作改善 AD 中受损的葡萄糖代谢，最终延缓疾病进展的机制。