Microbiota from Alzheimer's patients induce deficits in cognition and hippocampal neurogenesis.

Autor:	Grabrucker S; Department of Anatomy and Neuroscience, University College Cork, Ireland.; APC Microbiome Ireland, University College Cork, Ireland., Marizzoni M; Biological Psychiatry Unit, IRCCS Fatebenefratelli, Brescia, Italy.; Laboratory of Neuroimaging and Alzheimer's Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy., Silajdžić E; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, King's College London, SE5 9NU London, UK., Lopizzo N; Biological Psychiatry Unit, IRCCS Fatebenefratelli, Brescia, Italy.; Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy., Mombelli E; Biological Psychiatry Unit, IRCCS Fatebenefratelli, Brescia, Italy., Nicolas S; Department of Anatomy and Neuroscience, University College Cork, Ireland.; APC Microbiome Ireland, University College Cork, Ireland., Dohm-Hansen S; Department of Anatomy and Neuroscience, University College Cork, Ireland.; APC Microbiome Ireland, University College Cork, Ireland.; INFANT Research Centre, University College Cork, T12 DC4A Cork, Ireland., Scassellati C; Biological Psychiatry Unit, IRCCS Fatebenefratelli, Brescia, Italy., Moretti DV; Alzheimer Unit, IRCCS Fatebenefratelli, Brescia, Italy., Rosa M; Biological Psychiatry Unit, IRCCS Fatebenefratelli, Brescia, Italy., Hoffmann K; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, King's College London, SE5 9NU London, UK., Cryan JF; Department of Anatomy and Neuroscience, University College Cork, Ireland.; APC Microbiome Ireland, University College Cork, Ireland., O'Leary OF; Department of Anatomy and Neuroscience, University College Cork, Ireland.; APC Microbiome Ireland, University College Cork, Ireland., English JA; Department of Anatomy and Neuroscience, University College Cork, Ireland.; INFANT Research Centre, University College Cork, T12 DC4A Cork, Ireland., Lavelle A; Department of Anatomy and Neuroscience, University College Cork, Ireland.; APC Microbiome Ireland, University College Cork, Ireland., O'Neill C; APC Microbiome Ireland, University College Cork, Ireland.; School of Biochemistry and Cell Biology, BioSciences Institute, University College Cork, T12 YT20 Cork, Ireland., Thuret S; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, King's College London, SE5 9NU London, UK., Cattaneo A; Biological Psychiatry Unit, IRCCS Fatebenefratelli, Brescia, Italy.; Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy., Nolan YM; Department of Anatomy and Neuroscience, University College Cork, Ireland.; APC Microbiome Ireland, University College Cork, Ireland.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2023 Dec 01; Vol. 146 (12), pp. 4916-4934.
DOI:	10.1093/brain/awad303
Abstrakt:	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. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze:	MEDLINE
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