Antibiotics weaken the gut microbiome and can cause symptoms. Researchers have now discovered a natural therapeutic agent that is intended to protect the intestinal flora without affecting the effectiveness of the antibiotics.
Antibiotics are life-saving medicines. However, they can also destroy the beneficial microbes in the human gut and infections such as the bacterium Clostridioides difficile trigger. The pathogen is common in the human intestine, but normally does not cause any damage. However, when antibiotics are used, these bacteria can take over and cause dangerous gut problems as a result. Probiotics are often used for treatment, but they cannot keep up with the variety of native microbes and their functions.
Engineers develop protection
When antibiotics are given by mouth, the drugs enter the bloodstream mainly through the stomach, so they can continue to circulate in high concentrations in the body. Nevertheless, some traces also get into the intestine. However, if the effect is not needed there, the microbiome is in danger. MIT engineers have therefore developed a new method to protect the natural flora of the human digestive tract and to reduce the risks of antibiotic administration. To do this, they modified the bacterial strain Lactococcus lactis, which is normally used in cheese production and is safe for human consumption. When the bacterium is given orally, it temporarily settles in the gut and secretes beta-lactamase, an enzyme capable of breaking down beta-lactam antibiotics. After the work is done, the bacteria are then excreted again via the digestive tract.
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But the use of genetically modified bacteria harbors dangers: the beta-lactamase enzymes give the cells that house them antibiotic resistance. The tendency towards resistance can then easily be transferred to others via the genes of the bacteria. To solve this problem, the researchers recoded the bacterium and its way of synthesizing enzymes: To do this, they split the gene for beta-lactamase, each coding for a fragment of the enzyme, into two parts. These gene segments are located on different parts of the DNA, so it is very unlikely that both segments will be transferred to another bacterial cell at the same time. The beta-lactamase fragments are then transported out of the cell, where they reassemble and restore enzyme function. Because the beta-lactamase is so free to circulate in the environment, they become a freely available commodity for the gut microbiome. This is to prevent the manipulated cells from gaining an advantage over the native gut microbes.
Pleasing test results
The team tested the newly discovered therapeutic agent in a mouse model: one group of mice received only the antibiotic ampicillin, another group received two oral beta-lactamase doses in addition to each ampicillin dose. The researchers found that the mice that also received the biotherapeutic had much greater microbial diversity than the mice that received the antibiotic alone. In this group, microbial diversity dropped drastically. Furthermore, the mice from the antibiotic group showed high It’s hardlevels in the gut increased, while the beta-lactamase group did not develop any infections. But did the antibiotic remain effective despite the bacteria administration?
The researchers found that the amount of ampicillin circulating in the mice’s bloodstream remained the same whether the genetically engineered bacteria was used or just the antibiotic. “This is strong evidence that the bacterium’s approach can protect the gut microbiota while maintaining the effectiveness of the antibiotic,” explains lead author Dr. Andres Cubillos Ruiz. “No previous intervention has been able to provide this level of protection. With our new technology, we can make antibiotics safer by preserving the beneficial gut microbes and reducing the likelihood of new antibiotic-resistant variants emerging,” he continues. The researchers are now planning to further develop the therapeutic agent so that it can also be taken by humans.
This text is based on a press release from the Massachusetts Institute of Technology. We have the original publication for you here and linked in the text.
Image source: Katrin Leinfellner, unsplash.