Targeting microbes in the gut may prevent heart disease brought on by nutrients contained in diets rich in red meat, eggs and high-fat dairy products, scientists have found for the first time.
The discovery may represent a potential new therapeutic approach for the prevention of heart disease, as well as other metabolic diseases linked to gut microbes, such as diabetes, researchers said.
The new approach demonstrated by researchers from Cleveland Clinic in US centres around the research team’s previous discovery that TMAO (trimethylamine N-oxide), a byproduct formed in the gut during digestion of animal fats, is linked to atherosclerosis and heart disease.
Researchers identified a naturally occurring inhibitor called DMB (3,3-dimethyl-1-butanol) found in some cold-pressed extra virgin olive oils and grape seed oils – that reduced levels of TMAO and reduced atherosclerosis in mice.
The link between TMAO, gut microbes and heart disease was first discovered four years ago by the same team, led by Stanley Hazen, from the Cleveland Clinic.
“Many chronic diseases like atherosclerosis, obesity and diabetes are linked to gut microbes,” said Hazen, who is also Chair of the Department of Cellular and Molecular Medicine in the Lerner Research Institute.
“These studies demonstrate the exciting possibility that we can prevent or retard the progression of diet-induced heart diseases starting in the gut,” said Hazen.
TMAO is a gut metabolite formed during the digestion of the nutrients choline, phosphatidylcholine (lecithin) and carnitine, which are abundant in animal products.
Blood TMAO levels are associated with heightened risk of heart attacks, stroke and death in clinical studies.
Carnitine is abundant in red meat and liver, while choline and lecithin are abundant in beef, lamb, liver, egg yolk and high-fat dairy products.
The study suggests that targeted inhibition of the first step in TMAO generation, commensal microbial trimethylamine (TMA) production, can help to prevent diet-induced atherosclerosis.
The research team inhibited TMA production using DMB in mice fed a high choline or carnitine diet. The mice treated with the inhibitor had less TMAO and developed less atherosclerosis. DMB is not an antibiotic.
This important fact suggests that a treatment could target a specific microbial pathway while protecting the gut flora and avoiding antibiotic overuse and resistance, which is a worldwide health crisis.
“We were able to show that ‘drugging the microbiome’ is an effective way to block this type of diet-induced heart disease. The inhibitor prevents formation of a waste product produced by gut microbes, leading to lowering of TMAO levels and prevention of diet-dependent atherosclerosis,” said Hazen.
The study was published journal Cell.