Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice.
File(s)Kundu and Pettersson Manuscript_Science_RV1.pdf (1.73 MB)
Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2019-11-13
Date Acceptance
2019-05-20
Citation
Science Translational Medicine, 2019, 11 (518), pp.1-13
ISSN
1946-6234
Publisher
American Association for the Advancement of Science
Start Page
1
End Page
13
Journal / Book Title
Science Translational Medicine
Volume
11
Issue
518
Copyright Statement
© 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works http://www.sciencemag.org/about/science-licenses-journal-article-reuseThis is an article distributed under the terms of the Science Journals Default License (https://www.sciencemag.org/about/science-licenses-journal-article-reuse?_ga=2.207727826.1167138365.1574422970-494389306.1574263692)
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
UK DRI Ltd
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31723038
PII: 11/518/eaau4760
Grant Number
RDA27
4050641385
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
GROWTH-FACTOR 21
SODIUM-BUTYRATE
HIPPOCAMPAL NEUROGENESIS
STRESS
BRAIN
PERMEABILITY
HOMEOSTASIS
METABOLISM
EXPRESSION
DYSBIOSIS
Animals
Butyrates
Fecal Microbiota Transplantation
Fibroblast Growth Factors
Gastrointestinal Microbiome
Germ-Free Life
Hippocampus
Intestines
Liver
Longevity
Male
Metabolome
Mice, Inbred C57BL
Microtubule-Associated Proteins
Neurogenesis
Neurons
Neuropeptides
Phenotype
Proton Magnetic Resonance Spectroscopy
Intestines
Liver
Hippocampus
Neurons
Animals
Mice, Inbred C57BL
Butyrates
Fibroblast Growth Factors
Neuropeptides
Microtubule-Associated Proteins
Germ-Free Life
Longevity
Phenotype
Male
Metabolome
Neurogenesis
Proton Magnetic Resonance Spectroscopy
Gastrointestinal Microbiome
Fecal Microbiota Transplantation
06 Biological Sciences
11 Medical and Health Sciences
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-11-13