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Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients

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Title: Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients
Authors: D'Amato, A
Di Cesare Mannelli, L
Lucarini, E
Man, AL
Le Gall, G
Branca, JJV
Ghelardini, C
Amedei, A
Bertelli, E
Regoli, M
Pacini, A
Luciani, G
Gallina, P
Altera, A
Narbad, A
Gulisano, M
Hoyles, L
Vauzour, D
Nicoletti, C
Item Type: Journal Article
Abstract: Background The gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems; however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients altered the hippocampus, an area of the central nervous system (CNS) known to be affected by the ageing process and related functions. Results Young adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. We report that FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (Lachnospiraceae, Faecalibaculum, and Ruminococcaceae) and disorders of the CNS (Prevotellaceae and Ruminococcaceae) was observed. Finally, the detrimental effect of FMT from aged donors on the CNS was confirmed by the observation that microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype; on the contrary, gut permeability and levels of systemic and local (hippocampus) cytokines were not affected. Conclusion These results demonstrate that age-associated shifts of the microbiota have an impact on protein expression and key functions of the CNS. Furthermore, these results highlight the paramount importance of the gut-brain axis in ageing and provide a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions and the declining quality of life in the elderly.
Issue Date: 1-Oct-2020
Date of Acceptance: 31-Aug-2020
URI: http://hdl.handle.net/10044/1/87320
DOI: 10.1186/s40168-020-00914-w
ISSN: 2049-2618
Publisher: BioMed Central
Start Page: 1
End Page: 19
Journal / Book Title: Microbiome
Volume: 8
Issue: 1
Copyright Statement: © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Alzheimer's Research UK
Funder's Grant Number: MR/L01632X/1
MR/L01632X/1
ARUK-PPG2016B-6
Keywords: Science & Technology
Life Sciences & Biomedicine
Microbiology
GUT MICROBIOTA
BRAIN
DISEASE
RECOGNITION
IMPAIRMENT
MICROFLORA
EXPRESSION
MICROGLIA
DIVERSITY
SEROTONIN
Science & Technology
Life Sciences & Biomedicine
Microbiology
GUT MICROBIOTA
BRAIN
DISEASE
RECOGNITION
IMPAIRMENT
MICROFLORA
EXPRESSION
MICROGLIA
DIVERSITY
SEROTONIN
0602 Ecology
0605 Microbiology
1108 Medical Microbiology
Publication Status: Published
Open Access location: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532115/
Article Number: ARTN 140
Online Publication Date: 2020-10-01
Appears in Collections:Department of Surgery and Cancer



This item is licensed under a Creative Commons License Creative Commons