The gut microbiome consists of a wide variety of microbes and plays an important role in health, not just with the digestion of food, but also with many different physiological processes. The gut microbiome is currently the subject of extensive research to explore its impact on human metabolism, nutrition, physiology, and immune function.
Imbalances in the makeup of the gut microbiome can have a major impact on health, and those imbalances have already been linked to a wide range of syndromes and diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), type 2 diabetes, atopy, and obesity.
The gut microbiome can be altered by bacterial food poisoning and broad-spectrum antibiotics, which kill many of the beneficial bacteria and can permanently change the gut microbiome resulting in food intolerances or more serious problems. In such cases, reestablishing a more healthy balance of microbes could be hugely beneficial, but there are currently limited options for doing so. Fecal transplants have been shown to be beneficial in some patients. These treatments involve the reintroduction of beneficial bacteria taken from an individual with a healthy gut microbiome, but there are no guarantees that communities of beneficial bacteria will be established. The existing bacteria could outcompete the introduced bacteria, so these treatments may not be successful.
One approach for altering the gut microbiome is to use the CRISPR is a gene editing tool to alter the genetic makeup of specific microbes. Now, for the first time, CRISPR has been used to remove certain genes in Escherichia coli (E.coli) bacteria in the guts of mice and has allowed researchers to change the overall makeup of the bacterial communities in the gut. The CRISPR approach will allow researchers to study the gut microbiome in a much more controlled way than has previously been possible, and to make specific changes to the genomes of microbes to improve gut function and overall health.
E.coli is commonly found in the large intestines of mammals and helps the body to break down and digest food. E.coli and also competes with other microbes for nutrients, therefore providing a protective function against potentially harmful microbes. The strains of E.coli in the gut are usually harmless; however, some strains can cause food poisoning. The ability to edit the genomes of E.coli could lead to treatments that target the harmful strains while leaving the beneficial strains undisturbed.
The researchers used a virus called M13 to deliver a CRISPR-Cas9 system that had been engineered to target a specific strain of E.coli and remove key parts of the genome. M13 targets E.coli bacteria, although it does not survive well in the gut. The researchers altered the virus to include an antibiotic-resistant gene that the virus would deliver to infected cells, which helped the virus and the CRISPR-Cas9 system it was carrying to spread more easily. After treating the mice, the targeted E.coli strain was quickly eliminated, while the beneficial strains were unharmed. Within two weeks, the harmful strain was reduced to just 1% of the monitored cell population.
This is a landmark study, but considerable research is still required before this approach could be used in humans to alter the gut microbiome. Further viruses would need to be identified that could allow specific bacteria to be targeted, and more extensive studies are required to investigate how alterations to specific microbes in the gut affects the overall population of gut microbes.
“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,” said Peter Turnbaugh, Ph.D., a professor of Microbiology and Immunology at UC San Francisco. “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.”
You can read more about the study in the paper – Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome– which was recently published Cell Reports. DOI: 10.1016/j.celrep.2021.109930