Zajac Diana J, Shaw Benjamin C, Braun David J, Green Stefan J, Morganti Joshua M, Estus Steven
Department of Physiology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United States.
Department of Neuroscience and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United States.
Front Neurosci. 2022 Jul 4;16:873549. doi: 10.3389/fnins.2022.873549. eCollection 2022.
Elucidating the impact of the gut microbiome on Alzheimer's Disease (AD) is an area of intense interest. Short chain fatty acids (SCFAs) are major microbiota metabolites that have been implicated as a mediator of gut microbiome effects in the brain. Here, we tested the effects of SCFA-treated water vs. saline-treated water on APPswe/PSEN1dE9 mice maintained under standard laboratory conditions. Mice were treated with SCFAs from five months of age until ten months of age, when they were evaluated for microbiome profile, impaired spatial memory as evaluated with the radial arm water maze, astrocyte activation as measured by Gfap expression and amyloid burden as assessed by histochemistry and MSD ELISA. We report that SCFA treatment increased alpha-diversity and impacted the gut microbiome profile by increasing, in part, the relative abundance of several bacteria that typically produce SCFAs. However, SCFA treatment did not significantly affect behavior. Similarly, SCFAs did not affect cortical or hippocampal astrocyte activation observed in the APP/PS1 mice. Lastly, although robust levels of soluble and insoluble amyloid were present in the APP/PS1 mice, SCFA treatment had no effect on these indices. Overall, our findings are that SCFA treatment modifies the microbiome in a fashion that may increase further SCFA production. However, SCFA treatment did not alter behavior, astrocyte activation, nor amyloid neuropathology in APP/PS1 mice maintained with a conventional microbiome.
阐明肠道微生物群对阿尔茨海默病（AD）的影响是一个备受关注的领域。短链脂肪酸（SCFAs）是主要的微生物群代谢产物，被认为是肠道微生物群在大脑中发挥作用的介质。在此，我们测试了SCFA处理的水与生理盐水处理的水对在标准实验室条件下饲养的APPswe/PSEN1dE9小鼠的影响。小鼠从5个月大到10个月大接受SCFAs处理，在10个月大时评估其微生物群谱、用放射状臂水迷宫评估的空间记忆受损情况、通过Gfap表达测量的星形胶质细胞活化以及通过组织化学和MSD ELISA评估的淀粉样蛋白负荷。我们报告称，SCFA处理增加了α多样性，并通过部分增加几种通常产生SCFAs的细菌的相对丰度来影响肠道微生物群谱。然而，SCFA处理并未显著影响行为。同样，SCFAs对APP/PS1小鼠中观察到的皮质或海马星形胶质细胞活化也没有影响。最后，尽管APP/PS1小鼠中存在大量可溶性和不可溶性淀粉样蛋白，但SCFA处理对这些指标没有影响。总体而言，我们的研究结果是，SCFA处理以一种可能增加进一步SCFA产生的方式改变了微生物群。然而，在维持传统微生物群的APP/PS1小鼠中，SCFA处理并未改变行为、星形胶质细胞活化或淀粉样蛋白神经病理学。
