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Sci Transl Med. 2019 Nov 13;11(518). pii: eaau4760. doi: 10.1126/scitranslmed.aau4760.

Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice.

Author information

1
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore. parag.kundu@ips.ac.cn pkundu@ntu.edu.sg sven.pettersson@ki.se.
2
Singapore Centre for Environmental Life Sciences Engineering, Singapore 637551, Singapore.
3
The Center for Microbes, Development and Health, Key Laboratory for Microbiota-Host Interactions, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
4
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore.
5
Division of Computational and Systems Medicine, Department of Surgery and Cancer, Sir Alexander Fleming Building, Imperial College London, SW72AZ London, UK.
6
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore 117557, Singapore.
7
Duke-NUS Medical School, Singapore 169857, Singapore.
8
National Heart Research Institute, Singapore 169609, Singapore.
9
Penningtion Biomedical Research Center, Baton Rouge, LA 70808, USA.
10
Australian National Phenome Center, Murdoch University Perth, Perth, Western Australia, WA6150 Australia.
11
UK Dementia Research Institute at Imperial College London, Burlington Danes Building, Hammersmith Hospital, London, W12 0NN, UK.
12
Department of Neurobiology, Care Sciences and Society, Karolinska Institute, SE 17 177 Stockholm, Sweden.

Abstract

The gut microbiota evolves as the host ages, yet the effects of these microbial changes on host physiology and energy homeostasis are poorly understood. To investigate these potential effects, we transplanted the gut microbiota of old or young mice into young germ-free recipient mice. Both groups showed similar weight gain and skeletal muscle mass, but germ-free mice receiving a gut microbiota transplant from old donor mice unexpectedly showed increased neurogenesis in the hippocampus of the brain and increased intestinal growth. Metagenomic analysis revealed age-sensitive enrichment in butyrate-producing microbes in young germ-free mice transplanted with the gut microbiota of old donor mice. The higher concentration of gut microbiota-derived butyrate in these young transplanted mice was associated with an increase in the pleiotropic and prolongevity hormone fibroblast growth factor 21 (FGF21). An increase in FGF21 correlated with increased AMPK and SIRT-1 activation and reduced mTOR signaling. Young germ-free mice treated with exogenous sodium butyrate recapitulated the prolongevity phenotype observed in young germ-free mice receiving a gut microbiota transplant from old donor mice. These results suggest that gut microbiota transplants from aged hosts conferred beneficial effects in responsive young recipients.

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