Gut microbes may foster heart disease

Even the best of friends can be heartbreakers.

Friendly bacteria living in the intestines may contribute to heart disease just by helping digest dietary fats. Bacteria that break down a fat found in meat, dairy and some fish set off a chain reaction that leads to the buildup of an artery-clogging substance in the blood, say researchers from the Cleveland Clinic and their colleagues. The findings, published in the April 7 Nature, point to a new culprit in the hardening of arteries and may lead to new treatments for heart disease.

“We probably have underestimated the role our microbial flora play in modulating disease risk,” says Daniel Rader, a heart disease specialist at the University of Pennsylvania School of Medicine. Rader, who was not involved in the study, says that gut bacteria may not be as big a factor in causing heart disease as diabetes or smoking, but could be important in tipping some people toward sickness.

Researchers led by Stanley Hazen, a cardiologist at the Cleveland Clinic, didn’t start out to study gut bacteria. In fact, says Hazen, he had “no clue — zero,” that intestinal microbes were involved in heart disease. “I’d never even considered it or thought of the concept.”

Hazen and his colleagues compared blood plasma from healthy people to plasma from people who had had heart attacks, strokes or died to see if substances in the blood could predict who is in danger from heart disease. The researchers found 18 small molecules associated with fat buildup in the arteries. One of the best predictors turned out to be a by-product made when gut bacteria break down a fat called phosphatidylcholine (also known as lecithin).

The more of this by-product, called trimethylamine N-oxide or TMAO, a person or mouse has in the blood, the higher the risk of getting heart disease, the researchers found.

Gut bacteria are actually middlemen in TMAO production. The microbes convert lecithin to a gas that smells like rotten fish. Then an enzyme in the liver changes the foul-smelling gas to TMAO.

Mice genetically prone to get heart disease developed hardened arteries when fed lots of lecithin-rich egg yolks. But if the researchers eliminated most of the mice’s gut microbes with antibiotics, the animals didn’t get clogged arteries. The researchers don’t know exactly which types of gut bacteria make TMAO.

These findings show that the interactions of gut bacteria with diet can influence health, says Rader. The work also suggests that probiotics or drugs might be able to block TMAO production.

“This is very exciting, very novel work,” says Gabriel Nu±ez, an immunologist at the University of Michigan Medical School. But it remains to be seen if gut bacteria contribute in a big way to heart disease for most people, he says. The mice in the study are genetically prone to heart disease and were fed huge amounts of choline.

“The average person doesn’t look like these mice that you put on a high-fat diet and they develop plaques in a month,” Nu±ez says. He doesn’t doubt that gut bacteria may contribute to heart disease, but the effect could be small. More data are needed to determine how dangerous the combination of friendly bacteria and fat is to the heart.

Choline is an essential nutrient, but “We have no idea how much is too much,” Hazen says. Many multivitamins and other dietary supplements now contain choline, but eating large amounts of the substance might not be healthy. “Our data would suggest that’s a bad thing,” he says. “It suggests that’s like eating a tub of cholesterol.”