‘Drugging’
Gut Flora to
Prevent Heart
Disease?

“It’s a new approach to treating not just the individual Homo sapiens, but also the microbes that live with us and collectively contribute to disease,” says Dr. Stanley Hazen.

>> Here's a finding that gives new meaning (and a gender-neutral twist) to the old adage, "The way to a man's heart is through his stomach":

Stanley Hazen, MD, PhD, and his team at Cleveland Clinic recently discovered that targeting microbes in the gut may prevent heart disease caused by a diet high in animal fats — a finding that represents a potential new approach for treating the leading cause of death in the United States.

Drugging the Microbiome

>> Their novel approach centers around the team’s previous discovery of Trimethylamine N-oxide (TMAO), a byproduct formed in the gut during digestion of red meat, eggs and high-fat dairy products. Their research linked TMAO to atherosclerosis (hardening of the arteries) and heart disease, proving TMAO blood levels to be a powerful predictor of future heart attacks, stroke and death.

I’m not a vegan. I like a good steak.

More recently, the team identified a naturally occurring inhibitor called 3,3-dimethyl-1-butanol (DMB) — found in extra-virgin olive oil, grape seed oil, some red wines and balsamic vinegar — that reduced TMAO blood levels and atherosclerosis in mice. But it's the team’s approach, says Dr. Hazen, that really matters here.

“We were able to show that ‘drugging the microbiome’ is an effective way to block this type of diet-induced heart disease,” he says. “It’s much like how we use statins to inhibit cholesterol synthesis in human cells.

“"I kind of like to think of this as a statin for microbes.”

What’s Next?

>> Dr. Hazen contends there’s good reason to think DMB would work the same way in humans. And because DMB isn’t an antibiotic, the treatment potentially could target a specific microbial pathway without harming gut microbes or slowing their growth. Dr. Hazen hopes this would prevent the microbes from building up resistance to DMB — as they’d do eventually with antibiotics (i.e. a drug made to kill them).

“Many chronic diseases like atherosclerosis, obesity and diabetes are linked to gut microbes,” says Dr. Hazen. "If we replicate our findings in upcoming human studies, this could be a whole new approach to the treatment of cardiovascular and metabolic diseases." 

How You Can Help

>> Dr. Hazen’s research has been supported by grants and expedited by a term endowed chair “that was helping to provide discretionary money,” he says. When the term chair ends this year, Dr. Hazen will need additional philanthropic support to continue fast tracking his progress. 

“The entire discovery of the gut microbial link to heart disease wasn’t originally fundable by the National Institutes of Health because it was ‘too risky,’ and no one had ever heard of the connection,” Dr. Hazen says. “Drugging the microbiome to treat human diseases is just like that at this stage.”

Philanthropy, he says, makes projects like this possible. 

“Philanthropy gives us the freedom to take high-risk, high-reward leaps that would otherwise take years,” he says. It also creates a multiplier effect “by letting us jump way ahead to get preliminary data – enabling us to apply for grants that otherwise wouldn’t be available.”

Your generous support, says Dr. Hazen, “gives us the freedom to move forward at a rapid pace.”

Dr. Hazen is Chair of the Department of Cellular & Molecular Medicine at Cleveland Clinic's Lerner Research Institute, Section Head of Preventive Cardiology & Rehabilitation at The Sydell and Arnold Miller Family Heart & Vascular Institute and Chairholder of both The Leonard Krieger Chair in Preventive Cardiology and The Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis. 

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