Zeamer Abigail L, Lai Yushuan, Sanborn Victoria, Loew Ethan, Tracy Matthew, Jo Cynthia, Ward Doyle V, Bhattarai Shakti K, Drake Johnathan, McCormick Beth A, Bucci Vanni, Haran John P
Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Program in Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA.
bioRxiv. 2025 Mar 10:2025.03.06.641911. doi: 10.1101/2025.03.06.641911.
Disturbances in the gut microbiome is increasing correlated with neurodegenerative disorders, including Alzheimer's Disease. The microbiome may in fact influence disease pathology in AD by triggering or potentiating systemic and neuroinflammation, thereby driving disease pathology along the "microbiota-gut-brain-axis". Currently, drivers of cognitive decline and symptomatic progression in AD remain unknown and understudied. Changes in gut microbiome composition may offer clues to potential systemic physiologic and neuropathologic changes that contribute to cognitive decline. Here, we recruited a cohort of 260 older adults (age 60+) living in the community and followed them over time, tracking objective measures of cognition, clinical information, and gut microbiomes. Subjects were classified as healthy controls or as having mild cognitive impairment based on cognitive performance. Those with a diagnosis of Alzheimer's Diseases with confirmed using serum biomarkers. Using metagenomic sequencing, we found that relative species abundances correlated well with cognition status (MCI or AD). Furthermore, gene pathways analyses suggest certain microbial metabolic pathways to either be correlated with cognitive decline or maintaining cognitive function. Specifically, genes involved in the urea cycle or production of methionine and cysteine predicted worse cognitive performance. Our study suggests that gut microbiome composition may predict AD cognitive performance.
肠道微生物群的紊乱与神经退行性疾病，包括阿尔茨海默病的相关性日益增加。事实上，微生物群可能通过引发或增强全身炎症和神经炎症来影响阿尔茨海默病的疾病病理学，从而沿着“微生物群-肠道-脑轴”推动疾病病理学发展。目前，阿尔茨海默病认知衰退和症状进展的驱动因素仍然未知且研究不足。肠道微生物群组成的变化可能为导致认知衰退的潜在全身生理和神经病理变化提供线索。在这里，我们招募了一组居住在社区的260名老年人（60岁以上），并随时间跟踪他们，记录认知的客观指标、临床信息和肠道微生物群。根据认知表现，将受试者分为健康对照组或轻度认知障碍组。那些被诊断为阿尔茨海默病的患者通过血清生物标志物得到确诊。使用宏基因组测序，我们发现相对物种丰度与认知状态（轻度认知障碍或阿尔茨海默病）密切相关。此外，基因通路分析表明某些微生物代谢通路与认知衰退或维持认知功能相关。具体而言，参与尿素循环或蛋氨酸和半胱氨酸生成的基因预示着更差的认知表现。我们的研究表明，肠道微生物群组成可能预测阿尔茨海默病的认知表现。
