There are trillions of microbes in the human gut, and they can have a variety of impacts on our health and well-being. Scientists have been finding links between specific types of microbes and certain diseases, and also have been searching for ways to manipulate gut microbes to improve human health. In a new study, researchers have developed a genetically modified bacterium that aims to lower levels of a molecule that can cause kidney stones. This approach might also be a useful way to deliver other new biotherapeutic microbes to the gut. The work has been reported in Science.
It has been challenging to move beneficial microbes into the gut, and get them to make a home there. To overcome that challenge, investigators altered a known gut microbe called Phocaeicola vulgatus so that it would be at home in the gut. They scientists change it so that the bacterium would degrade a kidney stone causing substance called oxalate, and consume a nutrient called porphyran. In this way, the growth of the modified P. vulgatus could be controlled by modulating the levels of porphyran in the diet.
The modified microbe was tested in rats first, then in healthy individuals and finally, in patients with enteric hyperoxaluria (EH). This condition causes the body to take up too much oxalate, which leads to kidney problems and kidney stones unless it’s treated.
After finding success with their healthy rat model, the researchers tested it in a rat model of EH. The microbe was able to return oxalate levels in urine to a normal range, and the bacterium was eliminated when porphyran was removed from the diet.
The modified bacteria also worked in healthy humans, although it did persist in the gut in two of 39 study subjects, even after they were treated with antibiotics. The study authors suggested that the modified bacteria had shared genetic material with other microbes in the gut, and had mutated. However, there were no harmful effects detected in these individuals.
When the bacteria was given to a small group six EH patients, there was a reduction in symptoms but not a full elimination of their issues. Oxalate levels in urine dropped by an average of about 27% in six patients, which shows that the treatment may eventually work, but more research with larger sample sizes and improvement is needed for this method to work for patients.
Some of the bacteria given to the patients also mutated slightly, but no adverse events occurred in this group.
The study is a promising proof-of-concept, however, and has shown that it is possible to move engineered gut microbes into the gut, where they can colonize it. More work will be needed before scientists are rolling out biotherapeutic microbes in the clinic, but it may be possible to receive gut microbes as a treatment in the near future.
Sources: Medical Express, Science