Back to Search Start Over

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 :
Alfonsina D'Amato
Claudio Nicoletti
Lorenzo Di Cesare Mannelli
Eugenio Bertelli
Pasquale Gallina
Marì Regoli
Lesley Hoyles
Carla Ghelardini
Gwénaëlle Le Gall
Amedeo Amedei
Alessandra Pacini
Arjan Narbad
Giulia Luciani
Annalisa Altera
Massimo Gulisano
Angela L. Man
Elena Lucarini
David Vauzour
Jacopo Junio Valerio Branca
Medical Research Council (MRC)
Alzheimer's Research UK
Source :
Microbiome, Vol 8, Iss 1, Pp 1-19 (2020), Microbiome
Publication Year :
2020

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.

Details

Language :
English
ISSN :
20492618
Database :
OpenAIRE
Journal :
Microbiome, Vol 8, Iss 1, Pp 1-19 (2020), Microbiome
Accession number :
edsair.doi.dedup.....6c6571e12ecd0e3444b419241a1d16e9