In research published in the journal Nature Biotechnology, scientists report that they have managed to create molecules that decrease harmful bacteria in the gut. They succeeded in restoring gut bacteria balance and slowing down atherosclerosis in mice using the substances.
Atherosclerosis is a condition that involves the narrowing of arteries. It results from the buildup of plaque within blood vessels that carry oxygenated blood to different parts of the body. Narrowing stops the effective flow of blood to tissues and organs in need of it.
This disorder is a factor in the occurrence of two major death causes: heart attacks and strokes.
For years now, scientists have been looking toward recruiting gut bacteria for the fight against medical disorders.
The current study shows that gut microbiome could offer a potent means of reducing risk factors for heart attacks. One of the ways it can help in this regard is by decreasing cholesterol levels.
The team of scientists at Scripps Research developed molecules that restored the healthy balance of the gut microbiome in mice. The compounds called peptides lowered the number of unwanted gut bacteria, resulting in cholesterol reduction and atherosclerosis reversal.
Gut bacteria and health
The gut microbiome describes the super-abundant bacteria present in the digestive system. These microorganisms that run into trillions have a symbiotic relationship with humans or mammals. They get nutrients for their survival in the gut while also promoting the health of their hosts to an extent.
The evolution of the gut microbiome, which comprises several hundreds of bacterial species, took place long ago.
Scientists have taken more interest in understanding the microorganisms that are beneficial to their hosts in more recent decades. Their work shows that gut bacteria are helpful for digestion, metabolism, immune function, and brain health, among other functions.
At the same time, studies show that these microbes in the gut are a factor in health issues. They have been linked to disorders such as atherosclerosis, obesity, diabetes, and high blood pressure. Unfavorable changes to these bacteria play a role in these conditions.
Excessive use of antibiotics has been implicated in the disruption of the bacterial balance in the gut. Also, the consumption of Western diets that are high in calories and fats disrupts the gut microbiome.
Fighting atherosclerosis with peptides
Researchers in this study have been exploring the type of molecules used for years. They were hoping to use these to remodel the microbiome and so promote good health.
The Scripps Research team created a number of cyclic peptides with the aid of chemistry methods. It then proceeded to put together a screening system to assess the potential ability of the molecules to remodel the microbiome.
The ultimate aim of the team was to identify molecules that inhibit bad bacteria while leaving the beneficial ones unharmed. According to the scientists, nature inspired their use of small cyclic peptides.
“Our cells naturally use a diverse collection of molecules including antimicrobial peptides to regulate our gut microbe populations,” explained Luke Leman, Ph.D., co-senior author of the study and an assistant professor in Scripps Research’s Department of Chemistry.
For their experiments, the researchers used mice that were genetically engineered to be prone to high cholesterol. They then fed the animals with a Western-style diet, which resulted in adverse changes in their balance of gut bacteria. The diet resulted in elevated cholesterol levels and the narrowing of the arteries.
Next, the scientists applied each of the peptides to samples from the gut of the mice. They examined the samples the following day to identify specific cyclic peptides that promoted positive shifts in bacterial balance.
From their investigations, the researchers found that two of the molecules had notable effects on harmful species in the gut. These two peptides were used to treat mice on a Western-style diet and at risk for atherosclerosis, with impressive effects.
Blood cholesterol of treated animals showed a significant reduction, compared to those that were not treated. There was roughly a 30 percent reduction in cholesterol levels after a two-week treatment.
Also, the area of plaque in the arteries of animals that were given the molecules shrank by around 40 percent, compared to their peers that did not get the same. The team observed that much improvement after 10 weeks.
“It was surprising to us that simply remodeling the gut microbiome can have such an extensive effect,” said Professor Reza Ghadiri, Ph.D., a co-senior study author.
For their experiments, the team used drinking water to deliver the molecules to mice’s guts. The peptides pass through the digestive system without getting into the bloodstream.
No serious adverse effects were observed from the use of the peptides. Years of research revealed that the collection of molecules in this study is not toxic to cells in mammals.
These cyclic peptides seem to interact with the external membranes of target bacteria cells. They work in a manner that enables them to stop or slow the growth of these cells.
Ghadiri, Leman, and their colleagues are now exploring the usefulness of the molecules for another disorder following their positive findings. They are studying in mice how the peptides could help combat diabetes, a condition also linked to an imbalance of gut bacteria.