Phages, small viruses with big potential

Despite being nature’s most abundant and diverse biological entities, phages are still poorly understood. Natural predators of bacteria, they are found everywhere in the soil, the oceans... and in the human gut microbiota, where they are the dominant type of virus. We live in perfect harmony with them all through our lives. Of even greater interest is that they have significant potential to treat certain gastrointestinal diseases.

Promising discovery subsequently forgotten 

On being discovered in 1915, phages immediately aroused great interest for their ability to destroy certain bacteria responsible for infections. What’s more, in a specific way: each phage species targets (i.e. infects) a single bacterial species only. Experiments conducted since the end of the 1920s have shown satisfactory results for phage-based treatments in patients suffering from dysentery or cholera. “Phage therapy” was a serious contender to fight certain bacterial infections causing havoc at the time, before antibiotics took over in the 1940s. More effective and practical, antibiotics relegated phages to mere curiosity status. On the other hand, they are still used for therapeutic purposes in some Eastern countries. However, such therapies are poorly documented scientifically.

Phages make a comeback 

Today, the increase in antibiotic resistance has become a global health threat. Another concern is the impact of antibiotics on the balance of the gut microbiota, whose importance for health is now known. As a result, phages are back in the spotlight. Phage therapy trials have resumed over the past twenty years. After a few false starts, a study published in 2017 has caused a considerable stir. A diabetic patient infected with multidrug-resistant bacteria and suffering from pancreatitis went on to recover after five months thanks to phage therapy, following several failed treatments with antibiotics. Further successes in infections involving multidrug-resistant germs have since been reported. Except for a few very rare exceptions and despite the considerable hopes they raise, no treatment involving phages has been authorized by the health authorities to date.

The potential of phage therapy is not limited to the treatment of bacterial infections. It may also be used to correct microbiota imbalances (“dysbiosis (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) ”) associated with certain gastro-intestinal diseases, even non-infectious ones. For example, a study in mice showed the potential of phages to destroy specific intestinal bacteria associated with a poor prognosis in alcoholic hepatitis. Lastly, phages give cause for hope in the field of “precision” medicine. They could be used as “carriers” to deliver powerful drugs (e.g. chemotherapy) directly to a specific area of the body, allowing the treatment to be delivered solely to the cells/bacteria that need it. This would reduce the passage of the drug into the bloodstream, thereby curbing side effects and toxicity for neighboring organs.

Research underway to make phages our allies 

At present, a huge field of research is opening up in the hope of answering many questions, a century after the discovery of phages. Is phage therapy always safe? Can it replace antibiotic treatment? What is the right mode of administration and the right dosage? What long-term effects does phage therapy have on the microbiota? In addition to these numerous medical questions, there are regulatory constraints, as well as a legal vacuum in some countries that is surprising to say the least. Indeed, phages are neither drugs, vaccines, nor medical devices... making them inaccessible at present. This means there is a lot of work ahead, but according to the authors, it’s worth it.