New molecules rebalance gut bacteria to cut cholesterol in mice
Recent research is continuing to illuminate the role gut bacteria can play in all sorts of health outcomes, uncovering its ties with depression, obesity and various autoimmune diseases, just to offer a few examples. A new study has delved into their impact on cholesterol levels, detailing the "remarkable effects" of the introduction of a set of molecules that shift the balance of bacterial species in a way that prevents thickening of the arteries.
The study was carried out by scientists at Scripps Research who, like many other researchers in the field, were exploring how some diseases might be prevented by remodeling the communities of bacteria in our gut. Known as the gut microbiome, this dense population of trillions of bacteria plays an important role in maintaining the immune system, metabolism and other key functions of a healthy human body, but things like poor diet and use of antibiotics can upset the delicate balance and lead to adverse health conditions.
More specifically, the Scripps team was investigating how a typical Western diet packed with carbs, fats and sugars can reshape the gut bacteria in ways that drive high cholesterol and one of its flow-on effects known as atherosclerosis, the build-up of plaque and other substances on the artery walls. Atherosclerosis can lead to heart attacks and strokes in humans.
The study involved mice that were bred to be susceptible to high cholesterol, with the team feeding them a Western-style diet that promptly led to atherosclerosis along with changes to the gut microbiome. The team collected samples of the gut contents and introduced different types of molecules known as cyclic peptides, to see the effects they might have on the gut microbiome.
The next day, the scientists sequenced the bacterial DNA of the gut samples and found that two of the cyclic peptides had performed exactly the role they were hoping for, substantially slowing the growth of unwanted gut bacteria and promoting a healthy balance of species instead.
In further experiments, these peptides were used to treat atherosclerosis-prone mice on a high-fat diet, which led to a “striking” reduction in cholesterol levels in the blood, around 36 percent in just two weeks of treatment. Ten weeks of treatment led to a 40-percent reduction in atherosclerotic plaques in the arteries of the mice, compared to a control group.
The team believes the molecules work by interacting with outer membranes of some bacterial cells in a way that inhibits their growth. Enthused with these results, the researchers are now investigating the effects of the peptides on mouse models of diabetes, which is also thought to be connected to an imbalanced gut microbiome.
“It was surprising to us that simply remodeling the gut microbiome can have such an extensive effect,” says study co-senior author Reza Ghadiri, who went on to describe the effects as “remarkable.”
The research was published in the journal Nature Biotechnology.
Source: Scripps Research