4.8 Article

Gut microbiome pattern reflects healthy ageing and predicts survival in humans

Journal

NATURE METABOLISM
Volume 3, Issue 2, Pages 274-+

Publisher

NATURE RESEARCH
DOI: 10.1038/s42255-021-00348-0

Keywords

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Funding

  1. NCATS NIH HHS [UL1 TR000128] Funding Source: Medline
  2. NIAMS NIH HHS [U01 AR066160, R01 AR061445] Funding Source: Medline
  3. NIA NIH HHS [U01 AG042168, U01 AG042143, U19 AG023122, U01 AG042145, U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140] Funding Source: Medline

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The study finds that as individuals age, the gut microbiome becomes increasingly unique, with this uniqueness strongly associated with microbially produced amino acid derivatives in the bloodstream. Healthy older individuals continue to show microbial drift towards a unique compositional state, while less healthy individuals do not. Retaining high levels of Bacteroides dominance or having a low gut microbiome uniqueness measure predicts decreased survival in a 4-year follow-up.
The gut microbiome has important effects on human health, yet its importance in human ageing remains unclear. In the present study, we demonstrate that, starting in mid-to-late adulthood, gut microbiomes become increasingly unique to individuals with age. We leverage three independent cohorts comprising over 9,000 individuals and find that compositional uniqueness is strongly associated with microbially produced amino acid derivatives circulating in the bloodstream. In older age (over ~80 years), healthy individuals show continued microbial drift towards a unique compositional state, whereas this drift is absent in less healthy individuals. The identified microbiome pattern of healthy ageing is characterized by a depletion of core genera found across most humans, primarily Bacteroides. Retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicts decreased survival in a 4-year follow-up. Our analysis identifies increasing compositional uniqueness of the gut microbiome as a component of healthy ageing, which is characterized by distinct microbial metabolic outputs in the blood. Increasing compositional uniqueness of the gut microbiome, and corresponding changes in microbial metabolites in the blood, are identified as a signature of healthy ageing in humans.

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