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

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 sh...

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Bibliographic Details
Published in:Science translational medicine 2019-11, Vol.11 (518)
Main Authors: Kundu, Parag, Lee, Hae Ung, Garcia-Perez, Isabel, Tay, Emmy Xue Yun, Kim, Hyejin, Faylon, Llanto Elma, Martin, Katherine A, Purbojati, Rikky, Drautz-Moses, Daniela I, Ghosh, Sujoy, Nicholson, Jeremy K, Schuster, Stephan, Holmes, Elaine, Pettersson, Sven
Format: Article
Language:English
Subjects:
Age
Digestive system
Energy balance
Fibroblast growth factors
Gastrointestinal tract
Germfree
Homeostasis
Intestinal microflora
Intestine
Medicin och hälsovetenskap
Microbiota
Neurogenesis
Phenotypes
Skeletal muscle
Sodium butyrate
TOR protein
Transplants
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Summary: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.
ISSN:1946-6234
1946-6242
1946-6242
1946-3242
DOI:10.1126/scitranslmed.aau4760