Asthma and Bacteriophages – What We Know Now

What is a Bacteriophage

According to the U.S. National Institute of Health, Bacteriophages (or “phages”) are viruses that can kill or incapacitate specific kinds of bacteria while leaving other bacteria and human cells unharmed. By gathering naturally-occurring phages, or by modifying or engineering phages to display certain properties, researchers hope to create novel anti-bacterial therapeutics. Researchers connect Asthma and Bacteriophages.

Impact on Asthma

Staphylococcus aureus enterotoxins (intestinal toxins) have a demonstrated effect on airway disease including Asthma in early life according to multiple studies. These bacteria are in the gut and on the skin.

Because phages eliminate bacteria by infecting them, rather by generating compounds like antibiotics which kill bacteria, phages can be used to treat antibiotic-resistant infections. In addition, some evidence suggests that combination therapy containing both phages and antibiotics could prevent bacteria from becoming drug resistant.

Although scientists have been aware of phages and their ability to kill bacteria since 1917, the  first U.S.-based clinical trials of phage therapy have only recently begun. Individual U.S. patients have received phage therapy, but only under emergency investigational new drug protocols.  

World Asthma Foundation: Dr. Papadopoulos, what prompted your research into bacteriophages?

Asthma and Bacteriophages Video

Connecting Asthma and Bacteriophages

Dr. Nikolaos Papadopoulos: For many years, we have been working on the viral aspects of allergic diseases and particularly asthma based on the observation that most of the symptoms, especially the exacerbations of asthma, followed the common cold. There has been a link well-established, with lots of papers and lots of studying on the relationship of a particular virus, rhinoviruses with asthma exacerbations. Then there were more observations about associations, about bacterial infections, again in exacerbations.

Virus – Bacteria Interaction

We have discovered that the viral aspect also drives, to some extent, persistence of asthma, which means that viruses induce factors that trigger remodeling. Repeated infections might lead you to persistent asthma. Then we started looking at the interactions between viruses and bacteria. While we were looking at these specific micro-organisms, we realized that, as many other scientists did, we were actually focusing on our own little field without giving much attention to the wider perspective of the ecology of at least the local niche, the nose or the lungs where we have found in the last decade that you do have a growth of microbiome.

Lung Microbiome

In the past, we thought that in the lungs, there was no microbiome, but in fact, we know now that there is. Of course, there is increased interest generally in the microbiome and its disturbance, what we call dysbiosis in every condition. Then when we focus, we look at asthma. Wherever there is a focus on evaluating the microbiome in health and disease, there’s almost always this dysbiosis, this imbalance. We don’t know whether this is something that causes the disease or is a cause of the disease. However, it is very important to understand these characteristics.

Less Antibiotics

For us, it has been very important to place the different organisms and their interaction within a community and try to understand whether it’s possible, instead of trying to kill everything. That’s what we do with antibiotics. Instead of trying to eliminate our enemies, rather try to balance things and see whether we can have a community which is balanced and as considered resilient to external possible enemies. This is when and how we started looking into the meta-genome, and particularly the virion of the respiratory tract. That is how this all started.

World Asthma Foundation: What were the key findings?

Dr. Papadopoulos: Our observations so far, this is something I’ve been looking into more detail. As we expected, it is much more complicated rather than saying that one microorganism goes up and another one goes down. It’s much more about the ecology of the organisms rather than specific microorganisms.

Dynamics Between Microorganisms

I think this is a major understanding, a leap forward in that we shouldn’t think of microorganisms as individual forces that shape our internal microbiome health. It is the dynamic between microorganisms. It’s much more closer to health or disease because as you have one microorganism grow, then you have less resources for the other.

It is a balance, which is dynamic and happens all the time. This is where we got into bacteriophages in particular. This was something we did not expect. Also, it was not on the list of the viruses that we were focusing on because we’re focusing on the typical RNA viruses, the ones that harm, usually, like viral viruses of flu or RSV.

Bacteriophages As Main Player

Then we saw that the main player, one of the main players within the viral communities within the virion were the bacteriophages. In fact, and I think that’s our main finding, we’re the first to suggest is that there is a deficiency of bacteriophages in the upper respiratory tract, at least of children, this is where we have studied it.

Asthma and Bacteriophages 

We are now looking into different communities, different people, different geographies, et cetera, but the observation was repeated in another cohort. We don’t have many bacteriophages in an asthmatic airway. This is associated with looser network of microorganisms and less robust interaction network between the viruses and the bacteria.

Intervention With Phages

These key findings suggest that we might be able to intervene. This is a very good opportunity for intervention because we know that bacteriophages, mostly in most cases, they don’t harm.

They are in balance with the human host because they need to be there. It’s to both our benefits to control the bacterial populations for them not to overexpand. It’s a natural ally.

There is a possibility that we might be able to intervene using bacteriophages, but of course, this is not as straightforward as an antibiotic where you just give something, you kill whatever is susceptible and then it goes away.

We’re talking now about ecological balances. We need to understand exactly what type of bacteriophage you might need, what dose, at what time, et cetera. This is what we are actually doing now.

World Asthma Foundation: Thank you. What would you like asthmatics to know?

Dr. Papadopoulos: Well, we can look at the glass as half-full, as half-empty.

Glass Half Empty

The half-empty part is that for turning bacteriophage or different bacteriophages into therapy, we do need to do lots of things. Not only understand the mechanisms and select the bacteriophages, et cetera, but also, we have to overcome lots of regulatory hurdles because in our Western society, we can’t still use bacteriophages. They are living organisms. In order to standardize a living organism to provide it as medicine, it is really demanding.

Of course, there are all these questions and you’ve seen what happens now with the vaccines, even though most of them are not living organisms, still, it is very complex and we need to be very, very careful when we are exploring it.

Glass Half Full

On the other hand, what we are understanding of the half-full aspect is that by understanding the mechanisms and the dynamics of these microorganisms, we understand why healthy living, why being close to nature, why avoiding lots of pollutants makes us healthier in every aspect. This is also for people who have asthma.

Simple Advice

We know that some very simple and daily advice, like for example, being closer to nature, like eating healthy, for example, and avoiding things that generate pollution and things that generate inflammation is something that does improve their health.

I would suggest that asthmatics, as everybody else, should embrace the idea of a healthy environment and healthy people within this healthy environment.

Asthma and bacteriophages may soon be shown to be a very useful connection.

Bacteriophages research Dr. Nikolaos Papadopoulos reports.
Dr. Nikolaos Papadopoulos reports on bacteriophage research.