World Asthma Foundation “Defeating Asthma Series uncovers New Hope for Asthma Managementant
Our understanding of Asthma and the way we treat it may soon be radically different from what currently exists, due to new research on the human microbiome and how the microbiome affects asthma.
In this interview with Marie-Claire Arrieta Ph.D, Assistant Professor Depts. of Physiology and Pharmacology & Pediatrics Cumming School of Medicine University of Calgary Health Research Innovation Centre, Calgary, Alberta, Canada we learn that:
- A significant proportion of asthmatics have severe asthma that also cannot be controlled easily with the current treatments
- The microbiome is not only bacteria just like other ecosystems. Not only bacteria but they’re mix including environmental fungi
- The microbiome is full of viruses as well
World Asthma Foundation: Dr. Arrieta, what prompted your research in this area?
Dr. Arrieta: As you know, asthma has no known cures. A significant proportion of asthmatics have severe asthma that also cannot be controlled easily with the current treatments, so we’re trying to figure out ways of improving both the prevention and the potential therapies for asthma. We also know that asthma has become an epidemic disease in Canada. At least it’s quadrupled in incidence over only 30 years, and we know that it’s mainly environmental factors that are explaining or possibly explaining this really great increase in incidence for asthma.
We’ve come to learn in the past 10 years that the microbiome is implicated. The gut microbiome is this very large community of microbes that we all harbor in our inner guts. However, The vast majority of these studies of the microbiome and asthma have only included bacteria, including studies that I have participated in before. This only provides a part of the view of this vast variety of microbes that we know inhabit this microbial ecosystem.
The microbiome is not only bacteria just like other ecosystems. Not only bacteria but they’re mixed, and they definitely include fungi. We thought that studying the role of fungi would be important because molds and environmental fungi are quite common triggers of asthma attacks in asthmatics, also for people with allergies. This, we thought, may suggest that the fungi in the microbiome, that no one has been studying much before, may be involved in some of the immune education that happens early in life that may later in childhood lead to this uncontrolled inflammation in the airways towards environmental fungi, along with other environmental triggers of asthma. That’s why we wanted to look at fungi.
World Asthma Foundation: Excellent. Great study. I’m most impressed. What are some of the key findings?
Dr. Arrieta: We found by giving specific species or types of fungi and/or bacteria to mice, and we used a specific type of mouse known as the germ-free mouse. These are mice that are kept completely devoid of microbes, so they’re like a blank state that you can associate with microbes in a way that would allow you to then make good conclusions from the experiment.
We found that fungi have a very important role in the way the microbiome establishes early in life. When I say microbiome, now I mean a combination of both bacteria and fungi. We also found that fungi are sensed by the immune system differently than bacteria in a way that they seem to amplify the immune response. For example, we found that mice that were colonized only with fungi were more susceptible to asthma.
World Asthma Foundation: Interesting. Along with that, what were some of the other key findings?
Dr. Arrieta: The story’s definitely developing. This study was certainly a proof of concept, but based on this work as well as others that are starting to look at fungi too, we think that when fungi in the intestine of babies bloom, for example, during an antibiotic treatment, this may change the way the immune system responds to this microbiome that is now higher in proportion with certain fungi. This may also increase the susceptibility to those immune alterations that can later lead to asthma in certain people.
World Asthma Foundation: Interesting. I noticed that you mentioned several references to Candida albicans. How does that fit into the mix?
Dr. Arrieta: We don’t know yet. We chose Candida because it’s a very common yeast in our guts. Virtually everyone would have some candida in their bodies, not just in their guts, but it’s a very common inhabitant. Because of that, we wanted to use a species that was common. We found that Candida certainly can outgrow during antibiotic treatments. It may be one of the species implicated, but we’re not there yet. We’re now trying more species of fungi. In fact, we started a new set of experiments based on an infant clinical study that we just completed that showed us exactly which are the yeast and fungal species that bloom when babies are given antibiotics.
This was an interesting clinical study. We ran it at the emergency department of one of our children’s hospitals where we enrolled babies under six months of age, that for one reason or another had to take an antibiotic. This is a very common occurrence for infants. Then what we did was that we followed the microbiome during this antibiotic treatment, and we were able to identify the most common yeasts that seem to outgrow during the antibiotic treatment. We’re focusing on those, and surprisingly, Candida is not one of those all the time. It seems that, of course, Candida is there, but there’s other fungi that are able to outcompete other ones including Candida. Those are the ones that we’re focusing on now.
World Asthma Foundation: Thank you for that. By outcompete, the suggestion or the inference would be that the imbalance of fungi and bacteria are what’s causing the inflammation process?
Dr. Arrieta: That could be that case. That will be the next step, but as I said, the story is very much developing. I think we’re one of the first ones, but we’re not the only ones interested in studying the fungal component of the microbiome and how it relates to allergies and asthma. I think that in the next couple of years we’re going to learn a lot more.
World Asthma Foundation: Fair enough. What implications are there for asthma? Asthma rates are on the rise. What would you like asthmatics to know about your study?
Dr. Arrieta: For now, because the study is developing, I think what we know for sure is that the gut microbiome during early life is extremely important when it comes to, in general, immune development. Because asthma, of course, is an immune disease, these changes in the gut microbiome can certainly determine a baby’s risk to develop this disease, especially as we now understand in families that have a familial history of asthma as well.
What is important to asthmatics to know? There are certain lifestyle, changes, or behaviors that are now being recommended, including natural birth if, of course, is safe and possible, the use of breast milk over formula if it is possible. One of the things that we’re learning more about is that one of the ways to foster a healthy microbiome early in life is when babies start eating solid foods to make the diet as healthy as possible, the way nutritionists have been asking as to do so for decades now because this will foster a varied microbiome.
World Asthma Foundation: Good point. A fair amount of adult asthmatics suffer from fungal issues relative to lung inflammation and infection. Any thoughts on that?
Dr. Arrieta: There’s a couple of clinical studies, and I wish I remember from the top of my head the name of the drug exactly, that is being tested right now. I’m by no means, involved in this. I have just been reading it with great interest because it is an immune modulator. It’s a biological drug that targets some of the immune mechanisms that we now know recognize fungi. It’ll be really interesting to see now from the point of view of these patients, both children, and adults, that have fungal asthma, if this is really going to change their treatment options because as you know, those asthma tend to be more severe and harder to treat as well.
World Asthma Foundation: What would you like the scientific community to know about your research?
Dr. Arrieta: That within this revolution of studying that microbiome, I think we’re missing out by only focusing on bacteria. There’s a great deal that I have learned from my colleagues in microbial ecology. I am not an ecologist, but I started to partner up with them because of the methods and the concepts, and scientific frameworks that they used to study the microbiome. The microbiome is an ecosystem, and we have experts that have been studying ecosystems for decades before biomedical researchers started to study ecosystems. The inclusion of fungi, I think, will get us more answers. Also, the inclusion of other microorganisms that very few people, if any, are considering right now in the context of asthma research, which are viruses, very popular of course now because we’re under a pandemic. The microbiome is full of viruses and children experience many viral infections during the first year of life or the first two years of life. How does the immune system react to that? How does it get educated? I think that using a broader, more ecologically informed approach to study the microbiome is a lesson that I have learned over the years and I hope that others follow suit too.