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A new study determined how changes in the gut microbiome influence heart health and identified potential links between gut health and arterial dysfunction due to ageing.

Ageing is associated with a number of health challenges. Of many disorders that ageing presents, cardiovascular disease carries the greatest burden for the elderly population, their family members, and the health system. The elderly population is growing steadily. It is important for them to know about the structural and functional modifications such as stiffening of arteries that adversely affect heart health and increase the risk of cardiovascular disease.

How does ageing adversely affect heart health?

The main cause of deteriorating heart health with ageing is increased oxidative stress and chronic inflammation that leads to arterial stiffness and generalized endothelial dysfunction. Several studies have shown that diminished bioavailability of nitric oxide (NO), a key mediator of vascular relaxation, underlies endothelial dysfunction associated with ageing.

Ageing may also contribute to increased degradation of nitric oxide due to increased oxidative stress and inflammation. This creates a vicious cycle of inflammation, oxidative stress, and decreased the availability of nitric oxide, all the factors that adversely affect heart health.

The link between age-related arterial dysfunction and gut microbiome

There is a complex interplay between trillions of microbes living inside our gut and most of the systems of our bodies. This interplay plays an important role in our heart health.

The gut microbiome can contribute to heart disease in a variety of ways. When harmful bacteria leak through the intestinal lining into the bloodstream, they can lead to widespread inflammation. In addition, when certain bacteria are exposed to a high-protein diet, they produce harmful metabolites such as trimethylamine N-oxide or TMAO, that is linked to the formation of plaque in the arteries.

However, gut bacteria also produce short-chain fatty acids that protect the heart by regulating blood pressure. Therefore, a balance in the gut microbiome needs to be maintained so that the microbes work in favour of heart health.

Effect of ageing on the gut microbiome and heart health

A new study by the researchers at the University of Colorado Boulder determined how the gut microbiome modulates arterial function with ageing. The study recently published in the Journal of Physiology used young and old mice to identify a potential link between age-related arterial dysfunction and the gut microbiome.

The researchers gave broad-spectrum antibiotics to young and old mice to kill the bacteria living in the gut. After a few weeks of antibiotic treatment, the scientists assessed the health of vascular endothelium and the stiffness of arteries of the mice. They also measured levels of inflammatory markers, free-radicals, antioxidants, and nitric oxide in the blood of both young and old mice.

The old mice on antibiotics showed vast improvement in heart health

Three to four weeks of antibiotic treatment suppressed the microbiome of the old mice and restored arterial health to levels similar to young mice. While the old mice showed marked improvement in heart health, the researchers observed no changes in the vascular health measures of the young mice.

To assess the mechanism by which these microorganisms in old mice cause vascular dysfunction, the researchers genetically sequenced the fecal samples from mice. they compared the gut bacteria from old mice with that of young mice.

Ageing causes a lack of microbial diversity in the gut

Ageing causes a lack of microbial diversity in the gut that results in an imbalance of bacteria, also referred to as dysbiosis, which is associated with many age-related diseases. The genetic analysis of the gut microbiome of the old and young mice revealed how certain bacteria may be responsible for causing cardiovascular disease.

The researchers observed an increased prevalence of microbes that are pro-inflammatory and have been associated with certain diseases. For instance, the results of this study showed an increased prevalence of proteobacteria, a phylum that includes salmonella and other similar pathogens, and pro-inflammatory Desulfovibrioin old mice.

The researchers also measured the levels of metabolites produced by gut bacteria that get absorbed into the bloodstream. TMAO, a metabolite strongly linked to atherosclerosis, was found in much higher levels in the old mice compared to the young mice.

The researchers point out that the presence of certain bacteria in the gut is associated with high levels of TMAO. They suspect that ageing leads to dysbiosis and gut microbiota start to produce toxic chemicals such as TMAO leading to inflammation, oxidative stress, and tissue damage.

Maintain gut diversity to improve heart health in old age

The researchers are still investigating the role of diet in maintaining gut diversity. They, however, stress that using antibiotics to severely reduce gut bacteria is not a solution for preventing cardiovascular disease. Diets rich in probiotics such as yogurt, kimchi, and kefir as well as prebiotic fiber may improve heart health by promoting a healthy gut microbiome.

Researchers are optimistic that in the years to come there will be the development of dietary supplements that may improve heart health by blocking bacterial enzymes required to produce toxic metabolites such as TMAO.

In conclusion, this study highlights the association between age-related gut dysbiosis and the development of oxidative stress and inflammation that leads to adverse effects on heart health in the ageing population.

The future may hold promising therapies that will target the gut microbiome to prevent and treat age-related arterial dysfunction. In the meantime, following the old saying that the way to a man’s heart is through his stomach may hold new meaning in light of the findings of this study.

Written by Preeti Paul, MS Biochemistry

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Reference: Vienna E. Brunt et al., Suppression of the gut microbiome ameliorates age-related arterial dysfunction and oxidative stress in mice. J Physiol 00.0 (2019)pp1-18. Doi: 10.1113/JP277336


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