Nature 研究揭示常见肠道菌如何预防心脏病

A gut microbe that’s commonly found in humans manufactures a molecule that is capable of slashing cholesterol levels and shrinking plaque in arteries, according to a study published today in Nature¹.

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When given to mice, the compound, from the gut bacterium Bacteroides uniformis, reduced the animals’ arterial plaque by about half. It achieved the feat, researchers found, using the same biological action as that of statins, drugs that are prescribed to hundreds of millions of people worldwide to ward off cardiovascular disease.

The findings underline new ways in which people’s collection of gut microorganisms, known as their microbiome, might be harnessed to protect the heart, says study co-author Wenjing Zhao, a microbiologist at Sun Yat-sen University in Shenzhen, China.

The study provides “valuable evidence that the gut microbiome can influence vascular health”, moving beyond a simple link between heart disease and the microbiome, and towards “evidence for a potentially causal biological mechanism”, says Ben Chen, a cardiovascular specialist at Monash Victorian Heart Institute in Melbourne, Australia.

Matters of the heart

Diseases caused by atherosclerosis, the progressive build-up of inflammatory plaques in the walls of arteries, remain the leading cause of death globally. Although daily doses of statins have reduced the number of deaths, this alone fails to reduce cholesterol sufficiently in nearly half of people with advanced heart disease. And some people can’t tolerate high doses of the drugs.

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To find an alternative, Zhao and her colleagues analysed the gut flora present in stool samples from people with and without cardiovascular disease. One species stood out: B. uniformis. That’s because levels of the bacterium were often depleted in those with heart disease compared with in healthy individuals.

Next, researchers genetically engineered mice so that they developed atherosclerosis and fed them a high-fat diet to simulate the conditions in some people with heart disease. When the scientists administered live B. uniformis to the animals, it shrunk the plaques in their main arteries by about one-third, compared with the untreated mice. The bacterial dose also led to a drop in the levels of fatty substances in the blood, including total cholesterol and low-density lipoprotein (LDL), sometimes called ‘bad cholesterol’. Moreover, it reduced the amount of inflammatory immune cells infiltrating the rodents’ arterial walls.

Zhao and her colleagues isolated the molecule driving this protection: pentadecanoic acid. Further analyses showed that the molecule inhibits a liver enzyme involved in cholesterol production that is also targeted by statin medications. Blocking the enzyme triggers the liver to generate more LDL receptors, which in turn yank excess cholesterol out of the bloodstream.

To see whether the animal findings would translate to people, Zhao’s team examined blood and stool samples from more than 200 human donors. People with abnormally high concentrations of fatty molecules such as cholesterol in their blood had lower levels of pentadecanoic acid than did healthy individuals. Stool analyses also showed that people with heart disease carried fewer bacterial genes dedicated to manufacturing the molecule than did people in the control group.