Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients.
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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DOI：
10.1186/s40168-020-00914-w
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发表时间：
2020-10-01
期刊：
影响因子：
15.5
通讯作者：
Nicoletti C
中科院分区：
文献类型：
--
作者：
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
肠道-脑轴和肠道微生物区系正在成为健康和疾病的关键参与者。肠道微生物区系组成的变化影响各种系统；然而，它们对认知功能的直接影响的证据仍然缺乏。我们测试了从老年供体小鼠到年轻成年受体的粪便微生物区移植(FMT)是否改变了海马体，海马体是中枢神经系统(CNS)的一个已知受衰老过程和相关功能影响的区域。将来自老年或年龄匹配的供体小鼠的微生物群移植到年轻成年小鼠身上。移植后，进行了微生物群和代谢组学特征的表征，以及一系列认知和行为测试。无标记定量蛋白质组学被用来监测受者海马区的蛋白质表达。我们报告了来自老年捐赠者的FMT导致年轻成年受者的空间学习和记忆受损，而焦虑、探索行为和运动活动仍然没有受到影响。这与海马区参与突触可塑性和神经传递的蛋白质的表达变化是平行的。此外，与短链脂肪酸(SCFAs)产生相关的细菌(Lachnospiraceae、Faecalibaculum和反刍球菌科)以及中枢神经系统(Prevoteaceae和反刍球菌科)的紊乱也明显减少。最后，通过观察到海马伞的小胶质细胞获得了类似衰老的表型，证实了来自老年供者的FMT对中枢神经系统的有害影响；相反，肠道通透性以及全身和局部(海马体)细胞因子的水平没有受到影响。这些结果表明，与年龄相关的微生物区系的变化对中枢神经系统的蛋白质表达和关键功能有影响。此外，这些结果突显了肠道-脑轴在衰老过程中的至高无上的重要性，并为设计旨在恢复年轻微生物区系以改善认知功能和老年人不断下降的生活质量的疗法提供了强有力的理论依据。视频摘要
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. 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. 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. Video Abstract
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影响因子：
4.3
作者：
Bonaz B;Bazin T;Pellissier S
通讯作者：
Pellissier S
影响因子：
3.6
作者：
dos Santos, Eliseu Felippe;Brandt Busanello, Estela Natacha;Wajner, Moacir
通讯作者：
Wajner, Moacir
GLUT4 动员支持活跃突触的能量需求。
影响因子：
16.2
作者：
Ashrafi G;Wu Z;Farrell RJ;Ryan TA
通讯作者：
Ryan TA
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer