American researchers designed a potential new class of drugs that may reduce cardiovascular risks by targeting a specific microbial pathway in the gut.
A study published online on Monday in the journal Nature Medicine showed that the compounds could prevent gut microbes from making a harmful molecule linked to heart disease without killing the microbes, so unlike antibiotics, they would not lead to adverse side effects and resistance.
Cleveland Clinic researchers found that the new drugs reversed in mice model two major risk factors for cardiovascular disease, namely increased platelet responsiveness and excessive clot formation, by lowering levels of TMAO, a gut bacteria byproduct that forms during digestion.
TMAO is produced when gut bacteria digest choline, lechithin and carnitine, which are nutrients abundant in animal products such as red meat and liver.
The researchers previously found that TMAO affected platelet reactivity and clotting potential, leading to a higher risk of heart attack and stroke.
The compounds they designed are structurally similar to choline, so the bacterial cells are "tricked" into taking them up as nutrients.
Once transported into the microbe, they block the production of TMAO by inactivating a specific gut microbe enzyme called choline utilization protein C, according to the study.
They found that a single oral dose of one of the potent inhibitors in animal models significantly reduced TMAO levels in the blood for up to three days and reversed both enhanced platelet responsiveness and heightened clotting formation following arterial injury.
