A Gut Bacterium Makes a Molecule That Works Like a Statin, in Mice

Keypoints:

• A Nature study traces heart protection to the gut bacterium Bacteroides uniformis
• The bacterium makes pentadecanoic acid, which blocks a liver enzyme that statins also target
• Treated mice had smaller arterial plaques and lower total cholesterol and LDL
• People with heart disease had lower levels of the bacterium and fewer genes to make the molecule
• The human evidence so far is comparison, not treatment

A study published in Nature on 7 October describes a common gut microbe that protects the heart in mice. The bacterium is Bacteroides uniformis. It manufactures a molecule that cuts cholesterol and shrinks plaque in arteries. Nature's news report puts the plaque reduction at about one-third in the main arteries, while its summary cites about half.

The need is real. Atherosclerosis, the buildup of inflammatory plaque in artery walls, remains the leading cause of death worldwide. Statins have reduced deaths, but daily doses alone do not lower cholesterol enough in nearly half of people with advanced heart disease. Some people cannot tolerate high doses.

The team started with stool samples from people with and without cardiovascular disease. One species stood out. B. uniformis was often depleted in people with heart disease. The researchers then gave live bacteria to mice engineered to develop atherosclerosis on a high-fat diet. Plaques shrank, total cholesterol and low-density lipoprotein (LDL) fell, and fewer inflammatory immune cells entered artery walls.

The active molecule is pentadecanoic acid. It inhibits a liver enzyme involved in making cholesterol, the same one statins target. Blocking it prompts the liver to build more LDL receptors, which pull excess cholesterol out of the blood.

Human data point the same way. In blood and stool from more than 200 donors, people with high levels of fatty molecules had lower pentadecanoic acid. People with heart disease also carried fewer bacterial genes for making it. Cardiovascular specialist Ben Chen of the Monash Victorian Heart Institute said the work moves beyond a simple link toward a possible causal mechanism. The evidence still rests on mice and on comparisons in people. A human treatment trial would be the next test.