Though atherosclerosis is an artery problem, microscopic denizens of the intestines may play a surprising role in how the disease plays out.
A new study suggests that different mixes of intestinal microbes may determine whether people will have heart attacks or strokes brought on by break-away plaque from the arteries. Compared with healthy people, heart disease patients who have had strokes or other complications of atherosclerosis carry fewer microbes that make anti-inflammatory compounds. These patients also have more bacteria that produce inflammation-triggering molecules, researchers report online December 4 in Nature Communications. Inflammation is thought to promote cardiovascular disease.
The findings may help explain why people with higher levels in their body fat of antioxidant molecules like beta-carotene and lycopene have a lower risk of developing heart disease, but simply feeding people dietary supplements containing the compounds doesn’t help. It may be that a lifelong, intimate association with antioxidant-producing microbes helps some people stave off some of the worst consequences of hardened arteries.
Nearly everyone develops atherosclerosis with age. “We all have it to a certain extent,” says study coauthor Jens Nielsen, a bioinformatician at Chalmers University of Technology in Gothenburg, Sweden.
But some people are more susceptible than others to strokes and heart attacks, even though their arteries are no more blocked than the next person’s, says Fredrik Bäckhed, a microbiologist at the University of Gothenburg who also contributed to the study. The difference stems from the stability of the plaque that builds up inside blood vessels, stiffening and narrowing the vessels. When bits and pieces of plaque break off, they can block the flow of blood to the heart or brain and cause a heart attack or stroke.
Previous research suggests that gut microbes contribute to artery hardening by converting chemicals in fatty foods into artery-clogging substances (SN Online: 4/7/11). To determine whether intestinal bacteria also play a role in causing plaque to break away, Bäckhed, Nielsen and colleagues examined the microbial mixes in the feces of 13 healthy people and in 12 people with atherosclerosis who had experienced mild strokes, blocked blood vessels in the brain or temporary blindness due to clots blocking blood vessels of the eye.
Most people have one of three major types of bacterial communities, or enterotypes, inhabiting their intestines (SN: 5/21/11, p. 14). Stroke patients in the new study tended to fall into enterotype three, a community characterized by Ruminococcus bacteria. They also had more Collinsella bacteria species. In addition, bacteria in the guts of patients carried more genes for making peptidoglycan, a component of bacterial cell walls that can set off inflammation.
Healthy people’s feces were rich in Eubacterium, Roseburia and Bacteroides species. They also tended to have more Clostridium bacteria. Those bacteria often carry genes involved in making an anti-inflammatory molecule called butyrate. And healthy people’s microbes carry lots of genes for making other inflammation-reducing substances such as lycopene and beta-carotene, the researchers found.
“This is a tour de force of bioinformatics,” says Stanley Hazen, a cardiologist at the Cleveland Clinic who led previous work linking a person’s microbes to heart disease risk. The findings need to be replicated in larger groups of people, he says, but he will be excited to see studies that determine exactly what the bacteria are doing to promote health or disease.
One day, Bäckhed suggests, doctors may measure the microbial mix in their patients’ intestines and use that information, along with cholesterol and other factors, to better determine heart attack and stroke risk. “At this point, this is speculation and high hopes,” he says.
F.H. Karlsson et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nature Communications. DOI: 10.1038/ncomms2266
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