Key News in Family Medicine March 20, 2019 (11 of 12)

Why do blood vessels stiffen and degrade naturally with age, increasing the risk of cardiovascular disease? A new study from the University of Colorado at Boulder has identified a surprising new culprit who lives in your gut.

"This is the first study to show that changes in the intestinal microbiome due to aging have a negative impact on vascular health," said lead author, Vienna Brunt, a postdoctoral researcher in the Department of Physiology. integrative. "This opens a new avenue for potential interventions to prevent cardiovascular disease."

For the study published in the Journal of Physiology, the researchers administered broad-spectrum antibiotics to young mice and elderly mice to kill most of the bacteria living in their gut, ie their gut microbiome. Then they evaluated the health of their vascular endothelium (the lining of their blood vessels) and the stiffness of their large arteries.

They also measured blood concentrations of inflammatory compounds, damaging tissue free radicals, antioxidants and nitric oxide expanding blood vessels in both groups. After 3 to 4 weeks of treatment, the young mice did not notice any changes in vascular health. Older mice, however, have seen great improvements on all measurements.

"When you removed the microbiome from older mice, their vascular health was restored to that of young mice," said lead author and professor Doug Seals, director of the Integrative Physiology of Aging Laboratory. "This suggests that there is something about these microorganisms that causes vascular dysfunction."

The researchers then took stool samples from another group of mice and sequenced them genetically, comparing the intestinal bacteria of the aged mice to those of the young. "In general, in older mice, we found an increased prevalence of pro-inflammatory microbes badociated with diseases," said Brunt. For example, old mice harbored many more proteobacteria, a phyla that includes Salmonella and other pathogens, as well as pro-inflammatory Desulfovibrio.

To go further, the researchers measured the blood levels of metabolites – small molecules produced by the microorganisms of the intestine and absorbed by the blood – in old and young mice. Older mice had three times more TMAO (trimethylamine N-oxide), a metabolite demonstrated in previous studies as being linked to an increased risk of atherosclerosis, heart attack and stroke.

According to the American Heart Association, the risk of cardiovascular disease begins to increase as early as the age of 45. Between the ages of 60 and 79, 70% of Americans have it. After age 80, less than one in five are exempt. But what makes healthy arteries stiff and lose their function with age remains a medical mystery. "We've known for a long time that oxidative stress and inflammation contribute to unhealthy arteries over time, but we did not know why the arteries were starting to burn and get stressed. "said Seals. "We now believe that, with age, the gut microbiota begins to produce toxic molecules, including TMAO, that enter the bloodstream, cause inflammation and oxidative stress, and damage tissue."

The seals and Brunt insist that they do not at all suggest that antibiotics be used as a cardiovascular fountain. "We have only used antibiotics as an experimental tool.There are far too many side effects and other problems related to its extensive use," said Brunt.

But they believe that diets high in probiotic-rich foods (yogurt, kefir, kimchi) and prebiotic fiber may play a role in preventing heart disease by promoting a healthy gut microbiome. They are also studying a compound called dimethylbutanol, found in some olive oils, vinegars and red wines, which blocks the bacterial enzyme needed for the production of TMAO. In the end, it could be developed into a dietary supplement.

The paper, along with studies badociating an aging microbiome with GI, immune and brain aging, offers an additional reason to preserve the health of our resident bacteria, notes an editorial accompanying the journal's article. As its authors say: "The fountain of youth may be in the womb".