Dos Santos Guilherme Malena, Todorov Hristo, Osterhof Carina, Möllerke Anton, Cub Kristina, Hankeln Thomas, Gerber Susanne, Endres Kristina
Department of Psychiatry and Psychotherapy, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
Faculty of Biology, Institute for Developmental Biology and Neurobiology, Center of Computational Sciences Mainz, Johannes Gutenberg University Mainz, Mainz, Germany.
Front Microbiol. 2020 May 20;11:1008. doi: 10.3389/fmicb.2020.01008. eCollection 2020.
Alzheimer's disease (AD) is the most common form of dementia. Besides its cognitive phenotype, AD leads to crucial changes in gut microbiome composition in model mice and in patients, but the reported data are still highly inconsistent. Therefore, we investigated chronic effects of AD-characteristic neurotoxic amyloid-β (Aβ) peptides as provided by transgenic overexpression (5xFAD mouse model) and acute effects due to oral application of Aβ on gut microbes. Astonishingly, one-time feeding of wild type mice with Aβ provoked immediate changes in gut microbiome composition (β diversity) as compared to controls. Such obvious changes were not observed when comparing 5xFAD mice with wild type littermates. However, acute as well as chronic exposure to Aβ significantly affected the abundance of numerous individual operational taxonomic units. This provides first evidence that acute exposure to Aβ results in a shift in the enteric microbiome. Furthermore, we suggest that chronic exposure to Aβ might trigger an adaptive response of gut microbiota which could thereby result in dysbiosis in model mice but also in human patients.
阿尔茨海默病（AD）是最常见的痴呆形式。除了其认知表型外，AD还会导致模型小鼠和患者肠道微生物群组成发生关键变化，但报告的数据仍然高度不一致。因此，我们研究了转基因过表达（5xFAD小鼠模型）提供的AD特征性神经毒性淀粉样β（Aβ）肽的慢性影响以及口服Aβ对肠道微生物的急性影响。令人惊讶的是，与对照组相比，用Aβ一次性喂养野生型小鼠会立即引起肠道微生物群组成的变化（β多样性）。在将5xFAD小鼠与野生型同窝小鼠进行比较时，未观察到这种明显的变化。然而，急性和慢性暴露于Aβ均显著影响了许多单个操作分类单元的丰度。这首次证明急性暴露于Aβ会导致肠道微生物群发生变化。此外，我们认为慢性暴露于Aβ可能会触发肠道微生物群的适应性反应，从而可能导致模型小鼠以及人类患者出现生态失调。
