Gut microbiome genetically edited in live mice for the first time

Scientists at the University of California San Francisco (UCSF) have successfully edited the genome of bacteria in the gut microbiome of living mice, for the first time. Bacteria-hunting viruses are loaded with the CRISPR gene-editing system, in a breakthrough that could help manipulate the ratio between different bacterial species to treat a range of health problems.

Every one of us is carrying around an immense community of microorganisms in our gut. This gut microbiome is inextricably linked to your health, and not just digestive health, as might be expected. Recent research has found that the gut microbiome could play a role in autoimmune diseases, diabetes, cancer, cardiovascular disease, Parkinson’s, Alzheimer's, multiple sclerosis, and even depression.

The balance of this delicate ecosystem can be disturbed by our diet, antibiotics, and many other factors, and can be difficult to set right. Probiotics and fecal transplants may help, but they don’t always take and may not have the desired effect.

For the new study, the UCSF researchers investigated how gene-editing of gut bacteria could help restore balance to the microbiome makeup. An important distinction would be to design treatments that target specific strains of bacteria, without affecting others that may be beneficial.

“We’ve demonstrated the first stable gene edit within the gut microbiome of a mammal,” says Peter Turnbaugh, corresponding author of the study. “This is the starting point for trying to engineer bacteria within the gut.”

E. coli is one of the most common inhabitants of our guts, with strains that are good for us and others that can cause sickness like food poisoning. In tests in mice, the team engineered a bacteriophage called M13 – a virus that specifically hunts down E. coli – to selectively focus on one strain. When the virus latches on, it delivers the CRISPR-Cas9 to the target bacteria, deleting chromosomes.

The team administered M13 to mice orally, and monitored microbiome changes by analyzing the animals’ feces. Before treatment began, the target strain dominated their guts, but it accounted for just one percent of the population after two weeks.

The researchers say that the technique could eventually be used to alter the makeup of the microbiome to help correct imbalances that may cause health problems. But of course, that’s a lofty goal that’s still a long way off considering the sheer complexity of the microbiome. There’s still plenty of work to be done, including finding other bacteriophages that can target different bacteria.

“The dream is that you could just choose which specific strains in your gut – or even just individual genes – you want to promote or take out,” says Turnbaugh. “We’re really excited about how far we were able to push this in E. coli. Hopefully it will lead to similar tools for other members of the gut microbiota.”

The research was published in the journal Cell Reports.

Source: UCSF