Gut microbiome pattern reflects healthy ageing and predicts survival in humans

  • Nat Metab. 2021 Feb;3(2):274-286. doi: 10.1038/s42255-021-00348-0.
Tomasz Wilmanski  1 ,  Christian Diener  1 ,  Noa Rappaport  1 ,  Sushmita Patwardhan  1 ,  Jack Wiedrick  2 ,  Jodi Lapidus  2 ,  John C Earls  1  3 ,  Anat Zimmer  1 ,  Gustavo Glusman  1 ,  Max Robinson  1 ,  James T Yurkovich  1 ,  Deborah M Kado  4 ,  Jane A Cauley  5 ,  Joseph Zmuda  5 ,  Nancy E Lane  6 ,  Andrew T Magis  1 ,  Jennifer C Lovejoy  1  7 ,  Leroy Hood  1 ,  Sean M Gibbons  8  9  10 ,  Eric S Orwoll  11 ,  Nathan D Price  12  13
Affiliations
  • 1. Institute for Systems Biology, Seattle, WA, USA.
  • 2. Oregon Health and Science University, Portland, OR, USA.
  • 3. Onegevity Health, New York, NY, USA.
  • 4. Herbert Wertheim School of Public Health and Human Longevity Science at UCSD and Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
  • 5. Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
  • 6. Center for Musculoskeletal Health, Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA, USA.
  • 7. Lifestyle Medicine Institute, Redlands, CA, USA.
  • 8. Institute for Systems Biology, Seattle, WA, USA. [email protected].
  • 9. eScience Institute, University of Washington, Seattle, WA, USA. [email protected].
  • 10. Department of Bioengineering, University of Washington, Seattle, WA, USA. [email protected].
  • 11. Oregon Health and Science University, Portland, OR, USA. [email protected].
  • 12. Institute for Systems Biology, Seattle, WA, USA. [email protected].
  • 13. Onegevity Health, New York, NY, USA. [email protected].
PMID: 33619379 DOI: 10.1038/s42255-021-00348-0
Abstract

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.