In a recent study published in the journal Nature Medicine, researchers identified gut microbiota signatures and developed a microbial age metric, showing how younger microbial age may reduce cardiovascular disease (CVD) risk in metabolically unhealthy older adults.
Research Briefing: Gut microbial age modulates cardiovascular disease risk in metabolically unhealthy older people. Image Credit: FOTOGRIN / Shutterstock
Background
Age and metabolism are interconnected and contribute significantly to CVD, the leading cause of death globally. Gut microbiota may influence healthy aging by processing environmental signals, linking with host metabolism, and changing composition with age. However, the role of gut microbiota in long-term CVD risk amid aging and unhealthy metabolism is poorly understood due to the lack of defined microbial phenotypes and limited longitudinal data. Few metagenomic studies have explored this within a single population. Further research is needed to understand this interplay and develop targeted interventions to enhance cardiovascular health and promote healthy aging.
About the study
In the present study, researchers constructed five metabolic multimorbidity clusters (MCs) in a discovery cohort of 10,207 Chinese individuals based on 21 variables, including obesity-related measurements, blood pressure, insulin sensitivity, beta cell function, glucose, lipid parameters, and biomarkers of liver and kidney function. MC1 represented the metabolically healthy cluster, MC2 had low high-density lipoprotein cholesterol levels, MC3 had high low-density lipoprotein cholesterol levels, MC4 exhibited obesity-related features, and MC5 was characterized by hyperglycemia. During an 11.1-year follow-up, MC4 and MC5 exhibited 75% and 117% higher incident CVD risk, respectively, compared to MC1. These clusters and related CVD risks were replicated in an independent cohort of 9,061 Chinese individuals with a 10.0-year follow-up.
Gut microbial metagenomes from a subcohort of 4,491 individuals with a 6.8-year follow-up were analyzed, revealing divergent gut microbial compositions associated with older age and unhealthy metabolism (MC4 and MC5), accounting for confounders such as oral medications. A gut microbial age metric was developed based on 55 age-specific species to capture biological age and validated in four external cross-sectional datasets of 4,425 metagenomic samples from six countries.
Among individuals aged 60 and older in MC4 and MC5, a high microbial age exacerbated CVD risk, while a low microbial age, characterized by reduced Prevotella copri abundance, reduced this risk independent of chronological age, sex, educational attainment, lifestyle, dietary factors, and medication use. This suggests a modulating effect of microbial age on cardiovascular health in metabolically unhealthy older people.
Study results
The comprehensive design of the study allowed for in-depth investigations of gut microbiota signatures within the complexity of aging and metabolic multimorbidity. By rigorously controlling for potential confounders and ensuring robust findings through extensive validations, the study effectively highlighted the significant role of gut microbial age in modulating long-term CVD risk associated with unhealthy metabolism in older individuals. The results indicate that a younger microbial age, characterized by reduced Prevotella copri abundance, can effectively counteract the increased CVD risk linked to metabolic disturbances, independent of chronological age, sex, educational attainment, lifestyle, dietary factors, and medication use.
This discovery uncovers the potential of the newly developed gut microbial age metric in informing the application of microbiota-directed interventions to promote healthy aging and reduce CVD risk in metabolically unhealthy older populations. The findings suggest that targeting the gut microbiota to maintain a younger microbial age could be a viable strategy to enhance cardiovascular health and longevity in older adults.
The study underscores the importance of considering gut microbiota in the context of aging and metabolic health, paving the way for innovative approaches to manage and mitigate the risks associated with cardiovascular disease in older adults. The potential for microbiota-directed interventions offers a promising avenue for enhancing overall health and well-being in aging populations.
Conclusions
The study concludes that gut microbial age plays a significant role in modulating CVD risk in metabolically unhealthy older adults. A younger microbial age, characterized by reduced Prevotella copri abundance, effectively mitigates the increased CVD risk associated with unhealthy metabolism, independent of chronological age and other factors. This discovery highlights the potential for microbiota-directed interventions to improve cardiovascular health and promote healthy aging.