神经发生
肠道菌群
海马结构
阿尔茨海默病
认知功能衰退
神经科学
疾病
痴呆
失调
心理学
认知
医学
免疫学
内科学
作者
Stefanie Grabrucker,Moira Marizzoni,Edina Silajdžić,Nicola Lopizzo,Elisa Mombelli,Sarah Nicolas,Sebastian Dohm-Hansen,Catia Scassellati,Davide Vito Moretti,Melissa Rosa,Karina Hoffmann,John F. Cryan,Olivia F. O’Leary,James English,Aonghus Lavelle,Cora O’Neill,Sandrine Thuret,Annamaria Cattaneo,Yvonne M. Nolan
出处
期刊:Brain
[Oxford University Press]
日期:2023-10-18
卷期号:146 (12): 4916-4934
被引量:8
标识
DOI:10.1093/brain/awad303
摘要
Alzheimer's disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer's disease by showing specific alterations in the gut microbiome composition of Alzheimer's patients and in rodent models. However, it is unknown whether gut microbiota alterations are causal in the manifestation of Alzheimer's symptoms. To understand the involvement of Alzheimer's patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer's patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer's patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer's systemic environment on proxy neurogenesis readouts. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera. Our findings reveal for the first time, that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer's disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer's.
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