Engineered bacteria prevent antibiotics decimating the gut microbiome
An intriguing study led by researchers from the Massachusetts Institute of Technology has demonstrated how an engineered form of bacteria can protect the gut microbiome from the impact of antibiotic use. Mouse studies showed the bacteria breaks down antibiotics in the intestine while still allowing high levels of the drugs to enter the bloodstream.
Although antibiotics are inarguably one of the greatest medical discoveries of the last century they are also undeniably a blunt and imprecise tool. Researchers have long known antibiotics kill lots of beneficial bacteria on their way to target a specific infection but only recently have we begun to understand the implications of this.
New insights into the broader health effects of the trillions of bacteria living inside our gut have led researchers to recently uncover associations between a healthy gut microbiome and everything from immune system activity to mental health. So finding ways to protect that crucial bacterial population from the effects of antibiotics is more important than ever.
“Throughout your life, these gut microbes assemble into a highly diverse community that accomplishes important functions in your body,” explained lead author on the new study, Andres Cubillos-Ruiz. “The problem comes when interventions such as medications or particular kinds of diets affect the composition of the microbiota and create an altered state, called dysbiosis. Some microbial groups disappear, and the metabolic activity of others increases. This unbalance can lead to various health issues.”
The new research proposed a novel way to protect gut bacteria from the harmful effects of antibiotics. A strain of bacteria, Lactococcus lactis, was engineered to secrete an enzyme called beta-lactamase that can directly break down a common family of broad-spectrum antibiotics.
The researchers then tested the approach in a series of mouse models. The animals were given oral doses of the engineered bacteria alongside injections of a common antibiotic called ampicillin.
The tests revealed the engineered bacteria successfully made its way down to the animal’s intestine without disrupting the absorption of the antibiotic into the bloodstream. Once in the intestine, the engineered bacteria successfully protected the animals’ microbiomes from antibiotic damage.
“This is a strong demonstration that this approach can protect the gut microbiota, while preserving the efficacy of the antibiotic, as you're not modifying the levels in the bloodstream,” said Cubillos-Ruiz.
Another benefit to this kind of complementary bacterial therapy is that it can reduce the likelihood of antibiotic-resistant bacteria evolving. By eliminating the antibiotic molecules as they move through the intestine the researchers hypothesized this would reduce the selective pressure on antibiotic-resistant genes.
This hypothesis was proved correct in the animal tests. The mice not treated with the engineered bacteria displayed significantly higher levels of microbes with antibiotic-resistant genes compared to treated animals. Cubillos-Ruiz explained this means the treatment not only helps protect the gut microbiome from antibiotic damage but also reduces the chances for antibiotic-resistant bacteria to emerge.
“If the antibiotic action is not needed in the gut, then you need to protect the microbiota,” Cubillos-Ruiz said. “This is similar to when you get an X-ray, you wear a lead apron to protect the rest of your body from the ionizing radiation. No previous intervention could offer this level of protection. With our new technology we can make antibiotics safer by preserving beneficial gut microbes and by reducing the chances of emergence of new antibiotic-resistant variants.”
This kind of engineered bacteria therapy is still deeply experimental, and likely to not appear in clinical use for some time. The researchers suggest the next step for their work will be to optimize a version of the therapy to test in human subjects.
The new study was published in Nature Biomedical Engineering.
Source: MIT News