Valeri Francesco, Dos Santos Guilherme Malena, He Fuqian, Stoye Nicolai M, Schwiertz Andreas, Endres Kristina
Department of Psychiatry and Psychotherapy, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
The Center of Gerontology and Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China.
Microorganisms. 2021 Dec 9;9(12):2548. doi: 10.3390/microorganisms9122548.
Alzheimer's disease is a progressive neurodegenerative disorder affecting around 30 million patients worldwide. The predominant sporadic variant remains enigmatic as the underlying cause has still not been identified. Since efficient therapeutic treatments are still lacking, the microbiome and its manipulation have been considered as a new, innovative approach. 5xFAD Alzheimer's disease model mice were subjected to one-time fecal material transfer after antibiotics-treatment using two types of inoculation: material derived from the caecum of age-matched (young) wild type mice or from middle aged, 1 year old (old) wild type mice. Mice were profiled after transfer for physiological parameters, microbiome, behavioral tasks, and amyloid deposition. A single time transfer of cecal material from the older donor group established an aged phenotype in the recipient animals as indicated by elevated cultivatable fecal Enterobacteriaceae and Lactobacillaceae representative bacteria, a decreased Firmicutes amount as assessed by qPCR, and by increased levels of serum LPS binding protein. While behavioral deficits were not accelerated, single brain regions (prefrontal cortex and dentate gyrus) showed higher plaque load after transfer of material from older animals. We could demonstrate that the age of the donor of cecal material might affect early pathological hallmarks of Alzheimer's disease. This could be relevant when considering new microbiome-based therapies for this devastating disorder.
阿尔茨海默病是一种进行性神经退行性疾病，全球约有3000万患者受其影响。由于尚未确定其根本原因，主要的散发性变体仍然成谜。由于仍然缺乏有效的治疗方法，微生物群及其调控已被视为一种新的创新方法。对5xFAD阿尔茨海默病模型小鼠在抗生素治疗后进行一次性粪便物质转移，采用两种接种方式：来自年龄匹配（年轻）野生型小鼠盲肠的物质或来自1岁中年（老年）野生型小鼠的物质。转移后对小鼠的生理参数、微生物群、行为任务和淀粉样蛋白沉积进行分析。来自老年供体组的盲肠物质的单次转移在受体动物中建立了老年表型，表现为可培养的粪便肠杆菌科和乳酸杆菌科代表性细菌增加、通过qPCR评估的厚壁菌门数量减少以及血清LPS结合蛋白水平升高。虽然行为缺陷没有加速，但从老年动物转移物质后，单个脑区（前额叶皮质和齿状回）显示出更高的斑块负荷。我们可以证明，盲肠物质供体的年龄可能会影响阿尔茨海默病的早期病理特征。在考虑针对这种毁灭性疾病的基于微生物群的新疗法时，这可能具有重要意义。
