Editor of intestinal microflora

Researchers from the University of California, San Francisco, led by Peter Turnbaugh, have successfully used a DNA editing system to change the genome of bacteria living in the intestines of mammals, contributing to a better understanding of the microbiome. Ultimately, this may lead to the development of new methods of treating intestinal diseases.

Currently, researchers have extremely limited opportunities to change the microbiome. For example, food toxicoinfection can be treated with broad-spectrum antibiotics, but such drugs destroy non-pathogenic ("good") microbes along with pathogens. Fecal transplantation also does not meet expectations, as it does not give confidence that the injected healthy microbiome will be able to displace existing bacterial communities in the recipient's intestine, which means that treatment is not always successful.

The ability to change the DNA of microorganisms already in the intestine will allow us to study the microbiome in a more controlled way than was previously possible.

Turnbaugh's study was conducted on E. coli, a bacterium that naturally occurs in the intestine, but has a "dubious" reputation, since certain strains can cause food poisoning. One useful application of targeted gene editing in the gut microbiome would be to target pathogenic E.coli strains while leaving the beneficial ones intact.

In experiments on mice, the system was tested on a strain of E. coli labeled with fluorescein. The bacteriophage (virus that infects bacteria) M13 was used as a carrier of instruments for CRISPR-Cas9. It is embedded in the cell nuclei of a certain strain of E.coli, and removes DNA segments. After gene editing, the target bacteria began to disappear rapidly. After two weeks, they accounted for only one percent of the observed cell population.

The M13 phage, acting as a carrier of genetic scissors, usually survives poorly in the organs of the digestive system. To solve this problem, Turnbaugh and his colleagues embedded an antibiotic resistance gene in DNA that M13 would deliver to infected cells, allowing the virus – and the CRISPR-Cas9 system it carried – to spread more easily.

Turnbaugh suggests that editing bacterial genes directly in the gut may someday be used to stimulate the growth of "good" strains. For example, if researchers modified certain strains to feed on rare nutrients, a person could gain some control over the set of microbes thriving in his gut by simply adding foods containing these nutrients to his diet.

Article by K.N.Lam et al. Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome is published in the journal Cell Reports.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on UCSF materials: Infecting Gut Microbes with CRISPR-loaded Virus Demonstrates Potential for Microbiome Gene Editing.