Research ArticleGUT MICROBIOTA

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

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Science Translational Medicine  13 Nov 2019:
Vol. 11, Issue 518, eaau4760
DOI: 10.1126/scitranslmed.aau4760

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Hidden benefits of a fecal transplant

Our gut microbiota evolves as we age, yet its effects on host physiology are not clearly understood. Kundu et al. now attempt to elucidate these effects by transplanting the gut microbiota of either young or old donor mice into young germ-free recipient mice. They report that young germ-free mice receiving gut microbiota transplants from old mouse donors exhibited increased hippocampal neurogenesis, intestinal growth, and activation of the prolongevity FGF21-AMPK-SIRT1 signaling pathways in the liver. Subsequent metagenomic analysis revealed the potential role of butyrate-producing microbes in mediating these effects. These findings collectively suggest that the gut microbiota of an old mouse host may have beneficial effects in a young mouse recipient.

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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