Atherosclerosis is a chronic disease involving the build-up of plaque consisting of fat, cholesterol, calcium, and other blood-based substances. Sequentially, the plaque hardens and narrows the arteries to limit the flow of oxygen-rich blood around the body, leading to heart attacks, strokes, and even death. As heart disease and brain aneurysms are the second leading killer of people worldwide much money has been spent researching these pathologies. The gut microbiome is a symbiotic entity made up of thousands of different species of microorganisms living in our gastrointestinal tract contributing to many important functions within the host. A highly reactive bacterial colony, the gut microbiome instantly restructures in response to factors affecting its environment, such as diet or therapeutics, to aid in the development of several chronic diseases, including atherosclerosis. Now, a study from researchers at the Scripps Research Institute develops molecules capable of reducing unhealthy gut bacteria to reverse the narrowing of arteries in an animal study. The team states their cyclic peptide molecules remodeled the mouse gut microbiota into a healthier state to reduce cholesterol levels strongly inhibiting atherosclerosis. The study is published in the journal Nature Biotechnology.
Previous studies show when people overuse antibiotics or consume diets rich in carbs, fats, and sugar, the gut microbiome can be altered to promote disease. Indeed, it is well-established a microbiome depleted due to a diet high in fats and carbs can increase the risk of developing obesity, diabetes, hypertension, and atherosclerosis. This link has led to much work to identify techniques capable of remodeling the microbiome to roll back any adverse changes to restore good health. The current study engineers and tests cyclic peptides to alter the mouse gut microbiome to inhibit atherosclerosis.
The current study utilizes mice genetically predisposed to high cholesterol. The mice were fed a high fat and carb-loaded diet, leading to raised cholesterol-levels and atherosclerosis in the animals. The molecules developed and selected to alter the animals’ gut microbiota to a low-fat dietary status were imbibed via drinking water, traveling through the gut without entering the bloodstream, or causing any adverse side effects. Results show daily oral administration of the molecules in water reduced cholesterol levels and atherosclerotic plaques in the mice. Data findings show the peptide treatment successfully reprogrammed the microbiome to suppress the production of inflammatory cytokines, and improve the gut barrier integrity whilst increasing the level of immune cells in the intestine.
The lab states they significantly slowed the growth of undesirable gut bacteria in mice, changing the balance in favor of the species associated with a healthier diet. They go on to add their manufactured peptides produced favorable outcomes in atherosclerosis-prone mice fed a high-fat diet, with a marked reduction in the animals’ levels of cholesterol and atherosclerotic plaques compared to untreated mice.
The team surmises they have developed molecules possessing the ability to rehabilitate the intestinal microbiome, causing a stark reduction in blood-based cholesterol and arterial plaques. For the future, the researchers state they are now evaluating their peptides in diabetic mouse-models, a metabolic disorder linked to the debilitated gut microbiota.
Source: Scripps Research
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