Nav: Home

Drugging the microbiome may treat heart disease

December 17, 2015

A first-of-a-kind drug that interferes with the metabolic activity of gut microbes could one day treat heart disease in humans, according to a mouse study published December 17 in Cell. Dietary supplementation with a compound that is naturally abundant in red wine and olive oil prevented gut microbes from turning unhealthy foods into metabolic byproducts that clog arteries.

The findings suggest that a Mediterranean diet exerts its beneficial health effects by altering the activity of gut microbes. If replicated in humans, the study could lead to a new strategy for treating and possibly preventing heart disease and stroke--the top two causes of death worldwide.

"This study shows for the first time that one can target a gut microbial pathway to inhibit atherosclerosis," says senior study author Stanley Hazen of the Cleveland Clinic. "This new approach opens the door to the concept of drugging the microbiome to affect a therapeutic benefit in the host."

Atherosclerosis, commonly known as hardening of the arteries, has been linked to the consumption of high amounts of nutrients such as choline and carnitine, which are abundant in foods such as meat, egg yolks, and high-fat dairy products. Gut microbes convert these nutrients into a compound called trimethylamine (TMA), which in turn is converted by host enzymes into a metabolite called trimethylamine N-oxide (TMAO), which accelerates atherosclerosis in animal models and is associated with an increased risk for heart disease in humans.

Until now, efforts to target this pathway for therapeutic benefit have focused on inhibiting the host enzymes that convert TMA into TMAO. However, this approach causes liver damage as well as an unhealthy build-up of TMA. Hazen and his team figured that a more promising approach would be to directly target gut microbes to prevent the formation of TMA in the first place.

Toward this goal, Hazen and first author Zeneng Wang of the Cleveland Clinic screened for inhibitors of microbial TMA production from choline. They identified a compound called 3,3-dimethyl-1-butanol (DMB), which is naturally abundant in some cold-pressed extra virgin olive oils, balsamic vinegars, and grape seed oils. In mice that were on a choline-rich diet and genetically predisposed to atherosclerosis, DMB treatment substantially lowered TMAO levels and inhibited the formation of arterial plaques without producing toxic effects.

Additional experiments suggested that DMB exerted its beneficial effects by inhibiting TMA formation. Moreover, DMB did not kill the gut microbes, but it did reduce the proportions of some bacteria associated with high levels of TMA, TMAO, and atherosclerosis. "It was especially nice to see that the drug blocked the pathway without killing the microbe," Hazen says. "There should be less selective pressure for the development of resistance against a non-lethal drug than an antibiotic."

DMB treatment would also differ from cholesterol-lowering drugs such as Lipitor because it targets molecular pathways in gut microbes, not in human cells. "If we replicate our findings in upcoming human studies, this could be a whole new approach to the treatment of cardiovascular and metabolic diseases," Hazen says. "In the meantime, our findings suggest that it might not be a bad idea to consume a Mediterranean diet to help stave off heart disease and other health problems."
-end-
This research was supported by the National Institutes of Health and the Office of Dietary Supplement. Additional funding was received by the American Heart Association and the Leonard Krieger fund. Studies were performed on instrumentation housed within a facility partially supported by AB SCIEX. Three authors are co-inventors on patents held by the Cleveland Clinic relating to cardiovascular diagnostics and/or therapeutics. Stanley Hazen reports having been paid as a consultant and receiving research funds from several pharmaceuticals.

Cell, Wang et al.: "Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis" http://dx.doi.org/10.1016/j.cell.2015.11.055

Cell (@CellCellPress), the flagship journal of Cell Press, is a bimonthly journal that publishes findings of unusual significance in any area of experimental biology, including but not limited to cell biology, molecular biology, neuroscience, immunology, virology and microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. For more information, please visit http://www.cell.com/cell. To receive media alerts for Cell Press journals, contact press@cell.com.

Cell Press

Related Heart Disease Articles:

Arsenic in drinking water may change heart structure raising risk of heart disease
Drinking water that is contaminated with arsenic may lead to thickening of the heart's main pumping chamber in young adults, according to a new study by researchers at Columbia University Mailman School of Public Health.
New health calculator can help predict heart disease risk, estimate heart age
A new online health calculator can help people determine their risk of heart disease, as well as their heart age, accounting for sociodemographic factors such as ethnicity, sense of belonging and education, as well as health status and lifestyle behaviors.
Wide variation in rate of death between VA hospitals for patients with heart disease, heart failure
Death rates for veterans with ischemic heart disease and chronic heart failure varied widely across the Veterans Affairs (VA) health care system from 2010 to 2014, which could suggest differences in the quality of cardiovascular health care provided by VA medical centers.
Heart failure: The Alzheimer's disease of the heart?
Similar to how protein clumps build up in the brain in people with some neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, protein clumps appear to accumulate in the diseased hearts of mice and people with heart failure, according to a team led by Johns Hopkins University researchers.
Women once considered low risk for heart disease show evidence of previous heart attack scars
Women who complain about chest pain often are reassured by their doctors that there is no reason to worry because their angiograms show that the women don't have blockages in the major heart arteries, a primary cause of heart attacks in men.
Where you live could determine risk of heart attack, stroke or dying of heart disease
People living in parts of Ontario with better access to preventive health care had lower rates of cardiac events compared to residents of regions with less access, found a new study published in CMAJ (Canadian Medical Association Journal).
Older adults with heart disease can become more independent and heart healthy with physical activity
Improving physical function among older adults with heart disease helps heart health and even the oldest have a better quality of life and greater independence.
Dietary factors associated with substantial proportion of deaths from heart disease, stroke, and disease
Nearly half of all deaths due to heart disease, stroke, and type 2 diabetes in the US in 2012 were associated with suboptimal consumption of certain dietary factors, according to a study appearing in the March 7 issue of JAMA.
Certain heart fat associated with higher risk of heart disease in postmenopausal women
For the first time, researchers have pinpointed a type of heart fat, linked it to a risk factor for heart disease and shown that menopausal status and estrogen levels are critical modifying factors of its associated risk in women.
Maternal chronic disease linked to higher rates of congenital heart disease in babies
Pregnant women with congenital heart defects or type 2 diabetes have a higher risk of giving birth to babies with severe congenital heart disease and should be monitored closely in the prenatal period, according to a study published in CMAJ.
More Heart Disease News and Heart Disease Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.