Divergent age-associated and metabolism-associated gut microbiome signatures modulate cardiovascular disease risk
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
Methodological detailsdiscovery 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)
- Discovery and replication cohorts
- Shotgun fecal metagenomics
- External validation in four cohorts
- MA metric from 55 age-specific microbial species, validated in four external cohorts (4,425 metagenomic samples)
Main finding
As reported in the abstract
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.
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