Atherosclerosis is associated with consumption of specific nutrients such as choline and carnitine, abundant in foods such as meat, egg yolks, and high-fat dairy products. Gut microbes convert these nutrients into a compound called trimethylamine (TMA), which in turn is converted by host enzymes into a metabolite called trimethylamine N-oxide (TMAO), which accelerates atherosclerosis in animal models and is associated with an increased risk for heart disease in humans.
The study, by the Cleveland clinic, used a mouse model and a compound naturally abundant in red wine and olive oil, (predominantly found in the Mediterranean diet).
“This study shows for the first time that one can target a gut microbial pathway to inhibit atherosclerosis,” said study author Stanley Hazen of the Cleveland Clinic. “This new approach opens the door to the concept of drugging the microbiome to affect a therapeutic benefit in the host.”
The researchers used a compound called 3,3-dimethyl-1-butanol (DMB), which is naturally abundant in some cold-pressed extra virgin olive oils, balsamic vinegars, and grape seed oils. In mice that were on a choline-rich diet and genetically predisposed to atherosclerosis, DMB treatment substantially lowered TMA and inhibited the formation of arterial plaques without producing toxic effects.
“It was especially nice to see that the drug blocked the pathway without killing the microbe,” Hazen said. “There should be less selective pressure for the development of resistance against a non-lethal drug than an antibiotic.”
“If we replicate our findings in upcoming human studies, this could be a whole new approach to the treatment of cardiovascular and metabolic diseases,” Hazen said. “In the meantime, our findings suggest that it might not be a bad idea to consume a Mediterranean diet to help stave off heart disease and other health problems.”
The research findings indicate that a Mediterranean diet exerts its beneficial health effects by altering the activity of gut microbes.
“This study shows for the first time that one can target a gut microbial pathway to inhibit atherosclerosis,” says senior study author Stanley Hazen of the Cleveland Clinic. “This new approach opens the door to the concept of drugging the microbiome to affect a therapeutic benefit in the host.”
Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis, Wang et al., Cell, doi: 10.1016/j.cell.2015.11.055, published 17 December 2015.