Editing gut bacteria is the next frontier for CRISPR

Editing the genomes of our gut bacteria will “create a whole new field of biology” in the coming decades, a Nobel prize-winning geneticist has said at the opening of a London summit on the future of human genetic engineering.

Jennifer Doudna, from the University of California Berkeley, said that tweaking the DNA of the bacteria that live in our guts has the potential to help us understand and combat many diseases in humans.

Conditions from Alzheimer’s to asthma have been linked to the composition of our microbiome but the population of our gut is difficult to study and treatments designed to alter its composition so far are imprecise and based on taking faecal transplants.

Yet, said Doudna, there was a clear medical and scientific need to control the microbiome. “Microbiomes are increasingly indicated in all sorts of connections to human disease,” she said. “So for example, we know that there’s an important role of the human gut microbiome in diseases that include infections, and even neurodegeneration.”

Doudna helped create the precision editing technology known as Crispr, which has revolutionised the field of genetics, and could, she said, now be applied here too.

Crispr is going to enable not only some exciting individual applications, but really I think it will create a whole new field of biology because it’s going to open the door to understanding how these microbiomes behave in a way that has not previously been possible,” she said.

And not just in human guts. She argued that the technology might also have applications in animals, for instance by creating cows that produce less methane, a greenhouse gas. “In livestock, there is a powerful connection between the microbiome found in the cow rumen and the generation of methane. And surprisingly much of it is actually exhaled from these cows. It leads to about 30 per cent of the global annual emissions of methane,” Doudna said.

The possibilities for understanding and controlling gut bacteria offered by Crispr editing meant we should take it seriously. It was plausible, though, that it would first see genuine success in a different animal. “Having the ability to manipulate the cow rumen microbiome using Crispr would be an extraordinary advance, because we could actually change this in a calf, that would have an altered microbiome over the course of its entire lifetime,” she said.

Preliminary work suggested this was feasible, and had some surprising additional benefits, she said. “It reduces the methane emissions, which is very important. But also, it’s attractive to farmers because it means that there’s more efficient conversion of feed into food.”

Doudna was speaking in an opening video message for the 2023 Human Genome Editing Summit at the Francis Crick Institute in London. Delegates from around the world will consider the scientific, technical and ethical implications of their work. The field has rapidly matured in the past decade, thanks in a large part to Doudna’s technology.

Crispr works like molecular scissors, giving scientists the ability to seek out a strand of DNA, chop it out and replace it. Although editing of genomes was possible before, it was vastly more cumbersome.

Since its development in 2012, Crispr has become a standard laboratory tool, as well as a source of promising therapies. Among the other topics under consideration were the success of Crispr-based treatments to tackle sickle cell anaemia, a crippling genetic blood disorder. Approaches based on gene editing have produced significant success but the cost is prohibitive for much of the world, which is important because the condition is historically most prevalent in equatorial populations.