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The state of the gut microbiome may be as influential on health as exercise. The balance of microbial populations changes with age, in detrimental ways, for reasons that are not fully understood. The decline of the immune system, responsible for gardening the gut microbiome and defending intestinal tissue, may be one of the more important factors. With age, microbial populations producing beneficial metabolites decline in number, while populations contributing to chronic inflammation grow in number. There are interventions, such as fecal microbiota transplant, that can reverse these changes in a lasting way to improve health in animal studies, but as yet this strategy has yet to be introduced into human medicine as a treatment for aging.
Measurement of the gut microbiome is now readily accomplished via metagenomic techniques, and so scientists can begin to correlate the size and presence of microbial populations with the state of age-related degeneration. In today’s short open access commentary, researchers report on clear correlations between specific microbial populations and the aging of the heart, leading into cardiovascular conditions. The number of study participants is small, but it is nonetheless interesting data. More and larger studies of this nature should be undertaken, in combination with the development of therapies such as fecal microbiota transplantation, for widespread use in older people.
Distinct gut microbiota composition among older adults with myocardial ageing
Changes in cardiac structure and function occur with ageing and may lead towards ageing-related cardiovascular disease. Recent explorations into intestinal microbiota have provided important insights into shifts in microbial composition that occur in response to cardiovascular disease pathogenesis. Several proposed mechanisms include altered gut permeability, endotoxemia, and the systemic effect of metabolites including trimethylamine (TMA), short-chain fatty acids (SCFA), and secondary bile acids. However, causal associations between gut microbes and left ventricular (LV) function have yet to be proven. We sought to determine whether gut microbial composition is associated with left ventricular myocardial relaxation, an early manifestation of myocardial ageing, among older adults.
Among n = 15 participants (53% males, mean age 75 ± 4 years) recruited as part of a community-based research study on myocardial ageing, subjects with normal LV ejection fraction (60% and above) on baseline echocardiography were selected to undergo gut microbial composition examination in this proof-of-concept cross-sectional study. Myocardial ageing was assessed to be more impaired in those subjects with lower calculated ratios of peak early (E) to late diastolic (A, atrial contraction) velocities on Doppler echocardiography. We compared metagenomic reads between older adults with myocardial ageing (n = 8) vs. those without myocardial ageing (n = 7), based on E/A ratios.
Older adults with cardiac ageing had higher levels of several pathogenic gut bacteria. Ruminococcus, of the phylum Firmicutes, have been associated with higher C-reactive protein levels and higher pulse wave velocity. Certain Ruminococcus species are also capable of producing TMA, which has been linked to atherosclerotic disease and heart failure. Several Paraprevotella species, including P. xylaniphila, can produce pro-inflammatory metabolites, such as succinic acid, and is also associated with hypertension, metabolic diseases, and inflammatory diseases. Increase in gut Paraprevotella has been observed in association with the development of heart failure in mice.
Among individuals without cardiac ageing, we found higher levels of Firmicutes bacteria. Firmicutes are producers of SCFAs that regulate cholesterol levels, and some species have been associated with higher serum HDL. Reduced levels of Firmicutes were associated with LV hypertrophy and progression to heart failure in rats. In conjunction with higher levels of Bacteroidetes bacteria seen in our samples with cardiac ageing, we speculate that the balance between Firmicutes and Bacteroidetes (i.e., ratio) may be useful for studying gut microbial composition in relation to myocardial ageing in the future.