Cohort study

Divergent age-associated and metabolism-associated gut microbiome signatures modulate cardiovascular disease risk

Nat MedPublished

  • Prospective cohort study
  • discovery and replication cohorts
  • shotgun fecal metagenomics
  • external validation in four cohorts

Microbial age (MA) metric from 55 age-specific microbial species, validated in four external cohorts (4,425 metagenomic samples)

Authors' conclusion

This pattern, in which younger MA appears to counteract the CVD risk attributable to metabolic dysfunction, implies a modulating role of MA in cardiovascular health for metabolically unhealthy older people.

Study context

Population
Individuals aged 40–93 years classified into five metabolic multimorbidity clusters by 21 metabolic parametersdiscovery cohort
Participants
10,207 individuals
Exposure
Metabolic multimorbidity clusters (MC4, MC5) vs metabolically healthy cluster (MC1); modulation by gut microbial age
Outcome
CVD risk
Follow-up
11.1-year

Main finding

As reported in the abstract

multivariable-adjusted
Each group vs MC1Hazard ratio (95% CI)
MC4
1.75(1.43–2.14)
MC5
2.17(1.72–2.74)

Observational data: associations, not effects.

Further findings

Replication of MC–cardiovascular disease (CVD) associations (second cohort, n = 9,061) · 10.0-year follow-up

Associations replicated

Gut microbial composition (4,491 metagenomes)

Associated with both multimorbidity clusters (MCs) and age

CVD risk of MC4 or MC5 vs MC1, MC2 or MC3 by gut microbial age (MA), age ≥60 years (subgroup)

Increased CVD risk exacerbated with high MA, diminished with low MA, independent of age, sex, lifestyle and diet

Original publication

Divergent age-associated and metabolism-associated gut microbiome signatures modulate cardiovascular disease risk. Nat Med. Published 6 June 2024. doi:10.1038/s41591-024-03038-y

Summarised from the published abstract; every number is checked against it