Cardiovascular disease is the leading global cause of death, accounting for more than 17.3 million deaths per year, a number that is expected to grow to more than 23.6 million by 2030. About 2,200 Americans die each day from these diseases, and cardiovascular diseases claim more lives than all forms of cancer combined.

People who eat a lot of red meat have an increased risk for cardiovascular disease. The saturated fats and cholesterol in meat are thought to be culprits. But researchers have been unable account for the association, suggesting that other factors may be involved.

Now, researchers have demonstrated — for the first time — that targeting microbes in the gut may prevent heart disease brought on by nutrients contained in a diet rich in red meat, eggs and high-fat dairy products. An earlier study suggested the link between red meat consumption and heart disease may stem from gut microbes breaking down carnitine, a compound found in red meat.

The digestive system is home to trillions of microbes, or microbiota, that help break down our food, forming a variety of small compounds in the process. One of these compounds is trimethylamine, which can be metabolized to form trimethylamine-N-oxide (TMAO), which has been associated with atherosclerosis.

When a team of scientists, led by Dr. Stanley L. Hazen and Robert A. Koeth of the Cleveland Clinic, asked people to consume a beef steak and a carnitine supplement, regular meat eaters produced more TMAO than vegans or vegetarians. When participants took antibiotics to suppress gut microbes, they produced less TMAO after eating carnitine, suggesting that gut microbes are involved in the production of TMAO from carnitine. According to Hazen, the composition of bacteria living in our digestive tracts is dictated by our long-term dietary patterns.

The team next examined about 2,600 patients undergoing cardiac evaluations. They found that plasma carnitine levels were associated with the risk for heart disease and cardiac events such as heart attack, stroke and death. These relationships were only noted in people with high TMAO levels, suggesting TMAO is a key link between carnitine and cardiovascular risk.

To investigate further, the researchers studied germ-free mice with no pre-existing gut microbiota. They found these mice didn't make TMAO when first fed carnitine. However, when the mice were allowed to acquire conventional microbiota, carnitine feeding then led to TMAO formation.

Mice fed a diet supplemented with carnitine for several months showed evidence of altered intestinal microbes, a greater ability to produce TMAO from carnitine, and increased atherosclerosis. Parallel mice fed the same diet but given an antibiotic to suppress gut microbiota had lower plasma TMAO and no increase in atherosclerosis. In further experiments, the researchers found TMAO affects a major pathway for clearing cholesterol from the body, providing a potential mechanism for how TMAO might promote atherosclerosis.

The present study suggests targeted inhibition of the first step in TMAO generation — commensal microbial trimethylamine (TMA) production — can help to prevent diet-induced atherosclerosis. The research team inhibited TMA production using 3,3-dimethyl-1-butanol (DMB) in mice fed a high choline or carnitine diet. The mice treated with the inhibitor had less TMAO and developed less atherosclerosis.

DMB is not an antibiotic. This important fact suggests a treatment could target a specific microbial pathway while protecting the gut flora and avoiding antibiotic overuse and resistance, which is a worldwide health crisis.

Hazen was able to demonstrate that drugging the microbiome is an effective way to block this type of diet-induced heart disease. The inhibitor prevents formation of a waste product produced by gut microbes, leading to lowering TMAO levels and preventing diet-dependent atherosclerosis, much like how statins inhibit cholesterol synthesis in human cells.

Many chronic diseases like atherosclerosis, obesity and diabetes are linked to gut microbes, and these studies demonstrate the exciting possibility that we can prevent or retard the progression of diet-induced heart diseases starting in the gut. This opens the door for new types of therapies for atherosclerosis and other metabolic diseases.