New study reveals critical role of gut microbiome in aging and heart disease

In a recent study published in the journal Nature Medicinea group of researchers in China conducted a prospective cluster analysis of metabolic multimorbidity based on 21 metabolic parameters to investigate gut microbiome signatures associated with metabolism and age to better understand the relationship between metabolism, age, and long-term CVD risk.

Study: Divergent age-related gut microbiome and metabolic signatures modulate CVD risk. Image Credit: Katerina Kon / Shutterstock

Record

Cardiovascular disease is the leading cause of global mortality, and metabolic disorders and age, also complexly linked, are thought to be major contributors to cardiovascular disease risk. Metabolic disorders increase in complexity and prevalence with age, and the elderly commonly develop CVD in a multimorbidity setting.

Growing evidence on aging patterns associated with gut microbiome diversity among populations suggests that the gut microbiome links immunity and metabolism, undergoes age-related changes, and could underlie healthy aging. . Studies have found that the least diversity of Bacteroides and increased diversity of unique taxa in the gut microbiome were associated with healthy aging. However, the patterns of interaction between the gut microbiome, metabolism, and age and the extent to which these interactions influence cardiovascular health remain unclear.

About the study

In the present study, the researchers began by defining multimorbidity groups based on defined metabolic parameters and then investigated gut microbiome signatures associated with age and these multimorbidity groups. Then, based on variations in gut microbiome signatures and 55 age-related microbial species, they defined the concept of microbial age, which was then used to delineate the roles of gut microbiome composition and microbial age in specific multimorbidity groups.

The discovery cohorts included in this study consisted of adults between 40 and 93 years of age. In 2010 and 2014, data were collected on demographic characteristics, medical history, metabolic variables, and lifestyle factors such as alcohol consumption, smoking behavior, and physical activity levels. Follow-up data included information on the ascertainment of CVD events. Four faecal metagenomic datasets from populations from Israel, the Netherlands, France, Germany, the United States, and the United Kingdom were used as validation cohorts

Metabolic multimorbidity groups constructed based on 21 metabolic parameters were then associated with CVD risk. Parameters collected to define multimorbidity groups included body weight, height, waist circumference, high- and low-density lipoprotein levels (HDL-C and LDL-C, respectively), apolipoprotein A-1, total cholesterol, fasting insulin, apolipoprotein B, γ-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, oral glucose tolerance, uric acid, triglycerides, hemoglobin A1c and fasting plasma glucose.

Based on these parameters, five groups of metabolic multimorbidity were defined, including a healthy metabolic profile, as well as those defined by low levels of HDL-C and apolipoprotein A1, high levels of LDL-C, apolipoprotein B and total cholesterol, insulin resistance, obesity , elevated liver enzymes and hyperglycemia.

Stool samples were collected from all participants and shotgun metagenome sequencing was performed using the extracted deoxyribonucleic acid (DNA). Metagenomic data were used for metagenomic profiling of the discovery cohort.

Participants were divided into two groups based on age below or above 60 years, and hazard ratios for cardiovascular disease were calculated for the four unhealthy multimorbidity groups versus the healthy metabolic profile group. Hazard ratios for cardiovascular disease were also calculated for younger and older age groups.

The impact of environmental and host factors on the gut microbiome was assessed, after which the uniqueness and diversity indices for the gut microbiome were calculated. Gut microbiome characteristics that were related to age and metabolism were then examined, and associations between metabolism, microbial age, and CVD risk were determined.

Results

The results showed that compared with the healthy metabolic profile group, those classified as hyperglycemic and obese had a 117% and 75% increase in 11.1-year CVD risk, respectively. These findings were also replicated in the validation cohort.

Additionally, faecal metagenomic data revealed that gut microbiome composition was associated with both age and comorbidity groups. Furthermore, among people aged over 60 years, increased CVD risk associated with hyperglycemia and obesity multimorbidity groups was increased in those with higher microbial age and decreased in those with lower microbial age, independent of factors such as sex, age . , dietary or lifestyle factors.

Younger microbial age, which was characterized by reduced abundance Prevotella species, was found to neutralize CVD risk in older adults from metabolically unhealthy groups, independent of medication, dietary factors, education levels, sex, age, or lifestyle.

The study revealed several age-related gut microbiome signatures, including significant declines Bacteroides species and increased compositional uniqueness and richness of facultative anaerobic bacteria such as those belonging to Enterobacteriaceae and Streptococcus genera. The associated increase in pro-inflammatory pathways and these microbial aging patterns are thought to be linked to the age-related decline in immunity, digestion and physiological functions.

conclusions

In conclusion, the study examined the interaction between gut microbiome composition and richness, age and metabolism and its association with CVD risk. The study found that gut microbiome composition was associated with age and metabolic morbidity parameters.

Additionally, based on gut microbiome species composition, younger microbial age was found to moderate CVD risk associated with metabolic dysfunction, suggesting that the gut microbiome modulates cardiovascular health in older and metabolically unhealthy individuals.