21 March 2019

Microflora ages the arteries

As we age, human blood vessels lose elasticity and degrade, which leads to an increased risk of developing cardiovascular diseases. Researchers at the University of Colorado at Boulder, working under the guidance of Professor Doug Seals, have discovered a previously unknown and rather unexpected cause of this process.

A significant increase in the risk of developing cardiovascular diseases begins after 45 years, and according to the American Association for the Study of Heart Diseases, by the age of 60-79, about 70% of people are at risk, whereas after 80 years, even one in five cannot boast of a lack of risk. However, the reason why healthy arteries lose elasticity and functionality with age has remained a medical mystery until now.

According to Professor Sils, it has long been known that the age-related decrease in vascular functionality is due to oxidative stress and inflammation. However, why do the arteries become inflamed and undergo inflammatory stress? The authors decided to try to find the answer to this question in the intestine.

As part of their study, they gave young and old mice broad-spectrum antibiotics to kill most of the bacteria inhabiting their intestines. After that, they assessed the condition of the vascular endothelium (the inner lining of blood vessels) of the animals, as well as the elasticity of their large arteries.

In addition, the analysis of the blood content of both groups of animals of proinflammatory compounds, tissue-damaging free radicals, antioxidants and vasodilating nitric oxide was carried out.

After 3-4 weeks of therapy, the state of the cardiovascular system of young animals did not change, whereas in old animals there was an improvement in all the evaluated parameters.

According to Professor Sils, the destruction of the intestinal microflora of old mice restored the state of their cardiovascular system to the state characteristic of young animals. This indicates the existence of mechanisms by which microflora can cause vascular dysfunction.

In search of these mechanisms, the authors sequenced the genome in stool samples of another group of mice and compared the composition of the intestinal microflora of young and old animals. It turned out that, in general, the intestines of old mice contained a greater number of microorganisms that have a pro-inflammatory effect and were previously associated with the development of various diseases.

In particular, the microflora of old animals contained significantly more proteobacteria, which include salmonella and other pathogens, as well as pro-inflammatory bacteria of the genus Desulfovibrio, oxidizing hydrocarbons.

For a deeper study of the issue, the researchers measured the content of metabolites in the blood of young and old mice – small molecules produced by microorganisms and absorbed into the bloodstream through the intestinal walls. As a result, they found that the blood of old animals contains three times more TMAO (trimethylamine-N-oxide), the relationship between the concentration of which and an increased risk of atherosclerosis, myocardial infarction and stroke was demonstrated in earlier studies.

These observations lead to the conclusion that with age, the intestinal microflora begins to produce toxic molecules, including TMAO, which enter the bloodstream and trigger oxidative mechanisms and inflammatory processes that damage the vascular wall.

The authors emphasize that the use of antibiotics is not a way out. In the study, antibiotics were used exclusively as an experimental tool, whereas their widespread clinical use is associated with too many adverse events and other problems.

However, they believe that the introduction of probiotic-rich foods (yogurt, kefir, etc.) into the diet, as well as prebiotic fiber, can be an effective method of preventing cardiovascular diseases through improving the composition of the intestinal microflora. Recently, they started a clinical study aimed at studying the effect of different diets on the intestinal microflora and, accordingly, on the risk of developing cardiovascular diseases.

In addition, they are studying the properties of dimethylbutanol, a compound that is part of certain varieties of olive oil, vinegar and red wine. This substance blocks bacterial enzymes necessary for the synthesis of TMAO and may eventually become the active ingredient of new dietary supplements.

Article by Vienna E. Brunt et al. Suppression of the gut microbiome ameliorates age-related arterial dysfunction and oxidative stress in mice published in The Journal of Physiology.

Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Colorado at Boulder: Fountain of youth for heart health may lie in the gut.


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