Science1 publisherNot yet confirmed elsewhere1 min readPublished
A gut-bacterium fatty acid halved arterial plaque in atherosclerotic mice
Pentadecanoic acid, made by Bacteroides gut bacteria, cut arterial plaque in mice by about 50% by inhibiting HMG-CoA reductase, the enzyme statins target. The matching human evidence is so far only a correlation.
The Scientist · Science desk
What happened
- The team flagged Bacteroides uniformis because the microbe was depleted in the stool of people with cardiovascular disease compared with healthy donors.
- Feeding mice the live bacterium shrank plaques in their main arteries by about a third compared with untreated animals.
- The live dose also lowered total cholesterol and LDL and cut the inflammatory immune cells infiltrating the artery walls.
- Inhibiting the enzyme pushes the liver to build more LDL receptors, which pull excess cholesterol out of the bloodstream.
Compiled by The ScientistSomething wrong?How this is made
Why it matters
- capability A gut-made fatty acid that acts on the same enzyme as statins makes the microbiome a plausible source of new cholesterol-lowering compounds.
- exposure The patients this could reach are the ones statins underserve: nearly half of advanced heart-disease cases whose cholesterol stays too high, plus those who cannot tolerate high doses.
- constraint The causal effect sits in mice; whether giving people pentadecanoic acid lowers their cholesterol or plaque has not been tested.
Researchers gave mice the live bacterium, then ran bioactivity-guided screening of its metabolites to find the one responsible for the protection; it was pentadecanoic acid [8]. The study, published in Nature, counts microbiologist Wenjing Zhao of Sun Yat-sen University in Shenzhen among its authors [6][7]. To test that the fatty acid inhibits HMG-CoA reductase directly, the team docked it against the enzyme's human structure [1][11].
Pentadecanoic acid comes from more than one microbe. Across 100 strains the team screened, the capacity to make it turned up in several Bacteroidota genera [10].
To check whether the mouse result pointed at people, the team examined blood and stool from more than 200 donors. People with high blood cholesterol carried less pentadecanoic acid, and those with heart disease had fewer bacterial genes for making it [5]. Ben Chen, a cardiovascular specialist at Monash Victorian Heart Institute in Melbourne, said the study provides "valuable evidence that the gut microbiome can influence vascular health" and offers "evidence for a potentially causal biological mechanism" [18][19].
Atherosclerosis is the leading cause of death worldwide [14], and statins, prescribed to hundreds of millions of people to ward off cardiovascular disease, are the standard treatment [16]. The mice here were a disease model: genetically engineered to develop atherosclerosis and fed a high-fat diet to approximate advanced human disease [17].
What to watch
- A human trial testing whether pentadecanoic acid supplements lower LDL or arterial plaque.
- Whether a Bacteroides uniformis probiotic reproduces the effect seen with the live bacterium in mice.
- A measured enzyme-binding assay confirming the fatty acid inhibits HMG-CoA reductase beyond the computational docking.