In order to treat diseases, scientists have long tried to introduce genetically modified bacteria into the gut. In the past, these efforts have mostly concentrated on genetically modifying ordinary lab strains of E. coli, which are unable to compete with the native gut bacteria that are perfectly adapted to their host. The potential to treat diseases like diabetes has now been demonstrated by a team of researchers from the University of California, San Diego, who successfully altered E. coli isolated from the gut microbiomes of both mice and humans. On August 4, their findings will be published in the journal Cell.
“All I can say is “good luck” to the alien microorganisms. Since the gut microbiome is extremely dynamic and continually changing, the challenges faced by the alien bacteria are increased “According to senior author of the report and gastroenterologist at UC San Diego Health, Amir Zarrinpar. “With all of these unfriendly conditions that are oriented toward preventing bacterial invaders from taking root,” the author writes, “it is difficult for bacteria that have never lived inside of a mammal to now walk into the gut microbiome jungle.”
The team created a remedy for this issue by modifying E. coli obtained from the hosts directly. According to Zarrinpar, “Bacteria in our bodies are specially tailored to each of us: the types of foods we eat, the typical stresses our bodies undergo or produce, and our genetic heritage.” Their normal is this continually changing environment. Native bacteria benefit greatly from this and are therefore excellent candidates for engineering.
According to Zarrinpar, these bacteria have been modified to function as factories that can generate drugs and survive in human microbiome. “We know that E. coli can acquire pathogenic genes and cause disease, and now we’re just understanding that if we put a good gene in, it can allow us to treat chronic diseases, possibly even curing some of them,”
In order to further modify E. coli, the team first took samples of the host’s excrement. Zarrinpar explains, “We say to the bacteria: Hey, we’ll give you a new superpower, which you might not even use, but we’ll put you right back into the environment that you thrive in.
In order to further modify E. coli, the team first took samples of the host’s excrement. Zarrinpar explains, “We say to the bacteria: Hey, we’ll give you a new superpower, which you might not even use, but we’ll put you right back into the environment that you thrive in.
An enzyme called bile salt hydrolase is the protein that the team provided to these particular bacteria as a superpower (BSH). E. coli carrying BSH were discovered throughout the whole stomach of the mice after just one treatment, and they continued to produce BSH throughout the host’s lifetime. The team also demonstrates how BSH activity can prevent mice from developing diabetes.
This is a vast improvement over similar treatments using laboratory strains of created bacteria that are non-native, where many treatments are frequently necessary. Additionally, the native E. coli approach discovered by Professor Zarrinpar’s team does not consistently or for nearly as long as these modified bacteria do in the host’s stomach.
The team was able to modify E. coli taken from human gut in a manner comparable to how it effectively influenced diabetes in mice.
Even though they have shown significant successes, engineering native microorganisms has its own set of difficulties. According to Zarrinpar, “Native bacteria are extremely resistant to alterations; it is part of their intrinsic defence system.” Zarrinpar and his team are improving this procedure, but their statistics indicate that introducing a gene into a native bacterium has a 100-fold lower success rate than doing it with lab strain bacteria. The ability to more successfully build these microorganisms is now possible because to a variety of new genetic engineering methods, according to Zarrinpar.
The team hopes to use this technique to identify new ailments that can be treated. We have enormous dreams, adds Zarrinpar. “This technology has the potential to expand the use of microbiome therapy to treat a wide range of hereditary and chronic disorders.”