Hundreds of species of bacteria live and reign in the human gut. In the future, one of these species may have a new role: that of a microscopic “drug factory.”
A study published February 18 in the journal Nature Biotechnology (“Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage”) showed how gut bacteria can be reprogrammed to produce and release proteins in the lower gastrointestinal tract—finally solving a long-standing problem of transporting drugs to this “hard-to-reach” area of the body.
Why do gut therapies often miss their target?
Oral administration of drugs is the most common and practical way to get a drug to its “target” site. At least that’s the theory, because in practice, stomach acids don’t let anything pass “unscathed.” This is good when it comes to protecting the body from “enemies” like foodborne pathogens, but bad when it comes to gut-targeting therapies, as they often lose much of their effectiveness and are excreted without having accomplished their task.
Phage Hijacking
Bacteriophages attack bacteria in the following way: after attaching to the bacterial cell, they inject their DNA, essentially “hijacking” it and leading the bacteria to produce even more phages, which will ultimately lead to their extinction. When the bacterial cell finally succumbs to the attack, it explodes in a process called lysis, during which a “river” of phages is produced. When millions of such events occur simultaneously, there is a constant flow of a targeted protein into the lower intestine.
Given that phages play their own role in the gut microbiome, the research team thought of using them to introduce therapeutic proteins into the intestine.
Command to produce a therapeutic protein
They created special phages that inject a little extra genetic material into the bacterial walls. The bacterial cells, following the lysis process, produce new phages but at the same time receive an order to produce a therapeutic protein in the intestine.
Reducing inflammation and improving obesity
In order to prove the value of their method, the researchers used these modified phages to treat two different diseases in mice. Specifically, they saw that the approach led to:
Reducing inflammation by releasing a protein that inhibited the action of an enzyme associated with inflammatory bowel disease.
Improving obesity levels by releasing a protein that caused a feeling of satiety in mice that followed a high-fat diet that resembled a Western-style diet.
Exploring the commercial potential of the method
Having initially demonstrated the value of the new approach, the research team is now exploring its commercial potential through the I-Corps program of the US National Science Foundation.
