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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.
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World Asthma Day – May 5, 2021 – Spread the Word

World Asthma Foundation is supporting care of Asthma and asthmatics around the world. Please help those that suffer by spreading the word.

The WAF is doing it’s part by:

* Announcing the Defeating Asthma Project with the aim of shining a spotlight on getting to a cure

* Asthma education and advocacy for people with asthma who suffer

World Asthma Day May 5, 2021 Spread the Word

“We can move the needle by taking action now to make the difference for those that suffer from Asthma.” – Alan Gray, Director WAF Australia

We’ve hunkered down close to home here at the WAF. While doing so, we’re poring over volumes of available Asthma research data to share our understanding of the root causes of Asthma with emphasis on Severe Asthma.
Our ultimate goal is to understand the root cause of Severe Asthma (already considered a pandemic by many) while we aim for a cure. By banding together with other Asthmatics, including those that care about Asthmatics and clinicians that treat, we can defeat Asthma and we can do so now.

Why this Matters:

Asthma is not one disease but many and the causes underlying its development and manifestations are many including environmental issues

Asthma has reached pandemic levels around the globe

Asthma is a chronic lung disease that affects over 300 million worldwide

The projected rate will reach 400 million by 2025

Environmental exposures have been proven to play a significant role in the development of asthma and as triggers

Asthma is believed to be determined by a complicated set of one’s own genetics and environmental exposures including a multitude of toxic chemicals and the overuse of antibiotics

In the U.S., African Americans are almost three times more likely to die from asthma-related causes than the white population

Australia reported the highest rate of doctor diagnosed, clinical/treated asthma, and wheezing

Defining asthma remains an ongoing challenge and innovative methods are needed to identify, diagnose, and accurately classify asthma at an early stage to most effectively implement optimal management and reduce the health burden attributable to asthma

According to the U.S. Centers for Disease Control, The total annual cost of asthma in the United States, including medical care, absenteeism and mortality, was $81.9 Billion a year.

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Bacteriophages, Asthma, Airway Inflammation and Infection

To understand Bacteriophages and their role in airway inflammation, chronic infection and Asthma, World Asthma Foundation reached out to Dr. Bollyky, immunologist and infectious disease specialist at Stanford Medical Center for an introduction to these topics.

“Allergic disorders pose a growing challenge to medicine and our society. Therefore, novel approaches to prevention and therapy are needed. Recent progress in studies on bacterial viruses (phages) has provided new data indicating that they have significant immunomodulating activities. We show how those activities could be translated into beneficial effects in allergic disorders and present initial clinical data that support this hope.” – Society for Experimental Biology and Medicine

Introduction to Bacteriophages

World Asthma Foundation: Dr. Bollyky, can you introduce us to bacteriophages, their impact on chronic bacterial infections, airway inflammation and asthma?  

Video: Introducing Asthma and Bacteriophages – Airway Inflammation and Infection Interview with Dr. Bollyky, immunologist and infectious disease specialist at Stanford Medical Center

Dr. Bollyky: Yes, sure. First, just a little bit about the background of the lab and what we do. Then I’ll tell you about the bacteriophage we’re working on, and how we think it may relate to immune regulation, and airway inflammation in general.

We’re immunologists, as well as being infectious disease docs, and so my lab has worked now for a number of years trying to study immune regulation in the lung, and how populations of different regulatory cells sense allergens, and how they keep healthy folks from developing hypersensitivity to those allergens, and really where they go wrong in asthma. We’ve been doing that work about as long as I’ve been a professor at Stanford, which is about seven years. And a lot of that is funded by the NIH.

The other hat that I wear is as an infectious disease doc, and obviously anyone who has asthma will tell you that infections are among the triggers that seem to precipitate flares. 

There’s a lot of literature about asthma being related to flora, and to both episodic as well as long-term exposures to the microbial world. My lab studies a particular type of microorganism called the bacteriophage. These are viruses that are made by bacteria, and they are very abundant in your body as well as in your lungs, and really anywhere where bacteria tend to live. In the same way that you and I have viruses, your bacteria do too, and they produce these things in incredible amounts.

A fairly good rule of thumb is that you’re going to find somewhere in the neighborhood of 10 bacteriophages for every bacteria that you have at a site of chronic infection. The number is higher than that in sea water, but in most of the studies that have been done of the gut, or the oral tract, or the vagina, in spaces like this the numbers hold true. 

There’s less data in the lung, but I think you can be fairly confident that, again, anywhere where you’ve got long-term bacteria setting up shop, you have these phages. What we’ve been looking at recently is how your immune system sees these phages, and how they alter both the immune response to bacteria, but then sort of immune homeostasis in general.

One of the things that we found is that these phages tend to dampen responses to infection by bacteria, and they do that basically by being perceived as viruses, as you might expect, because that’s really what they are.

Phages and Asthma

World Asthma Foundation: How do  phages relate to asthma?

Dr. Bollyky: In two ways.

The first is, it may alter the microbiome of the lung and allow bacterial infections to persist, ironically longer than they might otherwise, because they keep immune clearance from happening. This may be counter-intuitive because most of us think of viruses as being bad for the host organisms, in this case bacteria, but both are probably true, meaning, bacteriophages are parasitized bacteria, but vis-a-vis the immune system they probably may also contribute to their persistence.

The other part about it, which is what we’ve been looking at recently, is how bacteriophages modulate the immune environment of the lung in general. There, it seems that, not unlike other viruses, that you see some interesting polarizing effects on immunity.

In all of this, there’s some very particular aspects of this that I think are relevant to the microbiome of the lung, and again, particularly to phages, but all of this highlights the complicated and, I think, fascinating immune and microbial environment of the lung in asthma, and how much we have to learn about that environment, and conversely, how many opportunities there would be to intervene in that system, if we only knew more.

Key Findings

World Asthma Foundation: What are the key findings?

Dr. Bollyky: A couple of things that folks who follow the literature will relate to. The first is there’s just been a lot more attention that’s being paid to the microbiology of the lung, and the idea – when I did my medical training, it’s getting close to 20 years now, what I learned at that time was that the lung was sterile, for example.

We know that that’s by far an oversimplification, and that there’s actually a lot of stuff going on there. Most of the past decade has been about characterizing the bacteria, and the fungi, and what have you, that are in the lung. Now, I think people are becoming alert, or attentive to the possibility, or to the fact that there are also endogenous viruses in these places, and that your lung has an ecology to it, where maybe not unlike, well, really any other ecology, the African Savanna, or your favorite fishing hole down the street.

There’s a lot of organisms that exist in competition, and in equilibrium at some points, and those are dynamic and living systems that we need to think about. That’s one trend, it’s just the attention to the microbiome and then the attention in particular to components of the microbiome.

I would put fungi in this, but also these bacteriophages that were relatively ignored until fairly recently, and then we’ve become kind of cognizant of what they do.

The other trend that I think is arising, that’s part and parcel of that in terms of asthma, is realizing that these different organisms, like fungi, like viruses and bacteria, exert opposing and, I think, important effects on the immune response, and that these things, the endogenous viruses you have, much like the endogenous bacteria, or the endogenous fungi can influence the ways that your immune system sees the rest of the world, and the ways in which it’s regulated.

Bacteriophages and Gut-Lung Interaction

World Asthma Foundation: We’ve been reporting on the Gut-Lung axis. Do you see that connection playing a role?

Dr. Bollyky: Yes, it’s a particularly interesting one too, because again, I think we tend to think of the lung in isolation, but the reality is that, both from above, in the form of your sinuses and secretions from there, but then also from below, meaning your gut.

Every time you sleep we know these secretions do go down. If you look at the microbiome of the lung, a lot of it tends to be oral flora, and a lot of it tends to be fairly transient, meaning, the studies that have been done would suggest that the bugs, the bacteria, and assuming it will probably be the case for the phages as well, but certainly the bacteria and the fungi that you have in your lung are fairly representative of the same organisms that you have in your sinus tract and in your gut. Your upper GI tract.

This ends up populating to a large extent your lungs. This big debate about whether your lungs are sterile or not really comes down to whether you think that these microbial interlopers are a part of a stable population or what their relationship is. As you are clearly aware, a lot of these same antibiotic resistance patterns, a lot of the same metabolites that your gut bacteria produces or that your sinus bacteria produce is going to end up in your lungs. Then, that’s going to influence the local immune response and ultimately asthma.

New Phage Research

World Asthma Foundation: Thank you Dr. Bollyky. What’s next?

Dr. Bollyky: We’re looking at phages and asthma models, and we’ve been studying a lot of infections, both human diseases like cystic fibrosis and in mouse models. Hopefully, I’ll be able to tell you more soon about phages and the allergens and regulatory T cell populations and that sort of stuff, and I’d love to come back.

World Asthma Foundation: We look forward to that. Thank you very much.

Dr. Bollyky: You got it.

See also Dr. Dietert’s interview about the Gut and Lung connection.

Find more information about Dr. Bollyky here.

Dr. Bollyky introduces bacteriophages, impact on chronic bacterial infections, airway inflammation and asthma
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Asthma and Bacteria: Nose to the Toes

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.

To further the WAF misson to improve our understanding of what drives Severe Asthma, the World Asthma Foundation reached out to Rodney Dietert, PhD, for his thoughts on the topic of Asthma and Staphylococcus aureus.

Rodney Dietert, PhD is a Cornell University Professor Emeritus, Health Scientist Head of Translational Science + Education for SEED, and the Author of the Human Super-Organism How the Microbiome is Revolutionizing the Pursuit of a Healthy Life.

This is the third in the series of interviews on the topic of Asthma and Staphylococcus aureus with Rodney Dietert, Phd.

Today We Learn About

* Staphylococcus aureus beyond the nose including the skin and the gut

Video Interview

Bacteria – Staph A and Asthma

World Asthma Foundation: Dr. Dietert, can we talk about Staphylococcus aureus and Asthma beyond the nose? 

Rodney Dietert, PhD: There are skin and gut microbiome effects on the Staph A asthma connection as well. It’s not just the nose but the nose is a good starting point.

Staph A, diet consumption, the bacteria that are in place, particularly in the nose, but also to some extent in the gut and even the skin, can determine what’s going to happen later in the risk for conditions like asthma. I think the thing to realize is that that bacteria and early on, that’s when you’re still recruiting cells. Lung maturation is one of the late-maturing systems. The lung and brain are late compared to a lot of other physiological systems. You don’t really fully mature the lung until something like 18 or 20.

Those effects on recruiting and getting balance in your immune cells in the lung are really important. When you’ve got a bacterium there that is producing allergens, it is stimulating a population we didn’t use to know about, called T helper 9. These cells produce a cytokine called Interleukin-9. The important thing to know is that these cells interact exquisitely with mast cells. They actually have T helper 9 cells.

Immune cells have histamine receptors so they’re co-stimulating between these cells and mast cells. Imagine (the outcomes) when an infant is skewed toward producing that kind of immune cells in these tissues, like the lung, and them having that kind of interactions with mast cells.

See also Dr. Dietert’s interview about the Gut and Lung connection.

Staph A bacteria - Dr. Dietert.

For full story and video follow the link below

Asthma and Bacteria: Nose to the Toes

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Asthma and Bacteria in Early Life

Staphylococcus aureus enterotoxins (intestinal toxins) have been demonstrated to affect airway disease including Asthma in early life according to multiple studies. The study of Asthma and Bacteria in early life is very interesting.

To further the WAF misson to improve our understanding of what drives Severe Asthma, the World Asthma Foundation reached out to Rodney Dietert, PhD, for his thoughts on the topic of Asthma and Staphylococcus aureus.

Rodney Dietert, PhD is a Cornell University Professor Emeritus, Health Scientist Head of Translational Science + Education for SEED and the Author of the Human Super-Organism How the Microbiome is Revolutionizing the Pursuit of a Healthy Life.

Asthma and Bacteria in Early Life: Staphylococcus Aureus

This is the second interview of three on the topic of Asthma and Staphylococcus aureus with Rodney Dietert, PhD. Today we learn about:

  • Relationship between Asthma and Staphylococcus aureus
  • Multinational studies on the topic of Asthma and Staphylococcus aureus
  • Importance of diet

 

Asthma and Bacteria in Early Life: Staphylococcus Aureus

World Asthma Foundation: Can you talk about the relationship between Staph A and Asthma as a biomarker in early life?

Rodney Dietert, PhD: Yes. There’s a multi-nation study that was done to look at the nasal microbiome in early life. They were measuring that two, four, six, nine months up through to two years and then looked, among their cohorts, at asthma between ages 6 and 18.

Nasal Microbiota Findings

What they found was really striking. They found four major categories of progression of the nasal microbiota as the infant aged. There was one of those groups where Staph A was the most prevalent bacterium or Staphylococcus, and particularly Staph A, that was present. The two-month major (bacterium). It was the main bacterium.

That group that started that way, at two months, had, I think it ranged from age 6 to 18, they were measuring asthma and that microbiome beginning (2 months). That contributed to 45 to 60% of the asthma among all of those children they were evaluating. Just from that one (microbiota) type. That was really an impressive predictor of asthma in later childhood. That suggests you don’t want to see Staph A like that, in a two-month-year-old baby. If you do, you better do something about it.

Staph A

Now, again, that is still an association but we understand what Staph A does to the immune system, because of what it does in terms of producing toxins that actually are allergens or can be allergens, what it does to IgE production. You know if that is really the prevalent nasal bacteria at that age and that is not what you usually see, that’s a problem. Right there, there is a biomarker in my opinion that should be a red flag. We should be looking to do something about that.

Sweet Consumption

There are also studies in early life that show consumption of sweets is a contributing factor to the risk when you’ve got Staph A in there. Some of the children actually seem to have a receptor detection of sweet issue. There’s a cohort that actually can’t tell that they’ve really had what would be considered an overabundance of sweets. They’re a little resistant to detecting it, so they eat more and that actually will propel them to severe asthma later on. That combination of Staph A, and diet even, is very important.

Asthma and Bacteria in Early Life: Staph A
Asthma and Bacteria in Early Life: Staph A, Rodney Dietert PhD

For additional information on Asthma and Staphylococcus aureus and the WAF defeating Asthma Project, visit:

Defeating Asthma Project

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Asthma and Bacteria Link says Study

To further the WAF mission to improve our understanding of what drives Severe Asthma, the World Asthma Foundation reached out to Rodney Dietert, PhD for his thoughts on the topic of Asthma and the bacteria Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a Gram positive (thick wall) bacterium that is believed to be carried by about one third of the general population and is responsible for common and serious diseases. A growing amount of medical literature suggest that Staphylococcus aureus enterotoxins (intestinal toxins)could affect airway disease including Asthma. 

Rodney Dietert, PhD is a Cornell University Professor Emeritus, Health Scientist Head of Translational Science + Education for SEED and the Author of the Human Super-Organism How the Microbiome is Revolutionizing the Pursuit of a Healthy Life

This is the first interview of three on the topic of Staphylococcus aureus with Rodney Dietert, Phd. We learn about:


* Connection between Asthma and bacteria Staph A
* Skin, nose and gut Microbiome
* Asthma and the immune system

World Asthma Foundation: Dr. Dietert, can you connect Staphylococcus Aureus or Staph A and Chronic Disease including Asthma for us?

Connection between Asthma and Bacteria Staph A: Video

Rodney Dietert PhD. connects Staph A and Asthma (and other chronic diseases)

Rodney Dietert, PhD: Yes, well, it’s very interesting because there’s a lot of research starting to come out on infectious agents and chronic diseases. We used to think that never the two shall meet but in fact, they do in many cases, either by inducing chronic diseases or by exacerbating those conditions.

Staph A, that is gram-positive bacterium, it is serious in terms of potential infections. We have it most often on the skin and in the nose. It can be either carried there or it can be a transient exposure. It also contributes to food poisoning. It’s one of the agents that, if contaminated, food can produce serious GI problems. It has a number of products that it makes including what are called enterotoxins or exotoxins. These can punch holes in cells. They can damage epithelial layers in the gut or in the airways.

They also are very interesting, in the case of Staph A or Staphylococcus aureus because some of these toxins can serve as allergens. They are actually sensitizing agents and that is the unknown, until recently, discovery, that when you’re looking for allergens that may contribute to asthma, you’d better include integral elements of that particular bacterium because that may be your allergen, that you may or may not have tested for.

World Asthma Foundation: Can you explain the interaction between the Microbiome, Staph A and Asthma?

Rodney Dietert, PhD:  Well, as with any potential opportunistic pathogen, the status of our microbiome in the body sites that carry it, and that would be where we’re exposed to the environment, so the airways, respiratory system, the skin, the gut, the urogenital tract, the status of that microbiome is incredibly important in terms of whether those pathogens can gain a foothold and then produce an infection. That is absolutely the case with Staph A.

Breaking the skin may give it (an opportunity to infect) , or surgery (as well). You have Staph A, and particularly drug-resistant Staph A, (as) a potential risk with surgeries but, (also) I mentioned food poisoning, breaking the skin. Also, dysbiosis, we call it, or a problem with the microbiome in the nose really can result in (Staph A problems), not just chronic sinusitis or reoccurring infections, but asthma. (The bacterium) can be inducing the condition, (and/or) it can be exacerbating already existing asthma.

Rodney Dietert, PhD: (Staph A) has been identified as one of the major culprits that is in the nose and where it can gain a foothold, (it) can produce some real problems.

World Asthma Foundation: What’s the distinction between infection and colonization in the context of Staph A and Asthma?

Rodney Dietert, PhD: Well, colonization is really where it’s able to attach to the proximity of the epithelium, or maybe directly to the surface. It can then produce its toxins and damage the epithelium and also have a nutrient source and spread. The thing to keep in mind is your friendly bacteria, your microbiota, that are mutualistic bacteria, or commensals they’re also called, the ones that we take as probiotics. Those actually have something like double-digit processes they can use to block pathogens like Staph A. Their being in place and metabolizing, in this case in the nose, is really important.

There is a recent really beautiful study that was published looking at early life and looking at colonization by bacteria in the nose and the prognosis for those children to develop asthma or not and some of the parameters related to that. That is where you can really see that starting to think about Staph A and asthma is critical immediately at birth and in the early few months. That’s where some of these distinctions are made and where, unfortunately, you can set up the immune system for inflammation in the lung.

World Asthma Foundation: You have a background in Immmunotoxicology. Can you define this role?

Rodney Dietert, PhD: Immunotoxicity is basically any environmental or external directed alteration to the immune system, in a negative way, damage to the immune system. That damage can take all kinds of different forms. Now, I have to say in my earlier years as a professor in the era of AIDS, HIV and AIDS, everybody thought, well, it’s all immunosuppression. My mantra has been, I contend that there are very few things that produce (only) pure immunosuppression. Something goes down and usually something else goes up (within the immune system) quite frankly. That part of what goes up is (often) allergy, autoimmunity, and inflammatory disease.

We used to measure, in the earlier days of immunology, we’ll measure things and say, “Wow, the antibody levels are reduced,” or something like that. We weren’t measuring more complex indicators for auto-immunity allergic diseases like asthma and psoriasis, inflammatory conditions. Had we been doing that (measuring the more complex indicators of immune-inflicted chronic diseases), we would see that some things we thought that were either immunosuppressive or not (and deemed safe), were not actually where the excitement (most significant risk) was for damage to the immune system.

The damage (connected to improper immune enhancement/balance) can (lead to) self-inflicted disease produced largely by immune cells (that are) out of control and misregulated. When you’re talking about asthma, that’s where you are.  (It) is (that) you have cells and mediators in the lung doing things out of balance that they shouldn’t be doing.

World Asthma Foundation: You advocate and have written extensively about Sustainable Healthcare. In fact, you write about the cost of chronic disease. Can you summarize the findings of the World Economics Council and Harvard study predicting that Chronic Disease will consume 48% of Global GDP by 2030?

Rodney Dietert, PhD:  That’s worldwide net worth, and we can’t afford it. If you’re thinking about healthcare being sustainable and being available for people in the future, for our children, for our grandchildren, then we’ve got to do things differently. We should do a better job of preventing chronic diseases like asthma and we certainly should do a better job of managing these (chronic diseases) with the life course in mind.

When a child presents with asthma, the pediatrician quite frankly, in my opinion, should be asking, “What can I do for that child today? What can I do to prevent comorbid diseases 10, 20, 30, 40 years from now?” I think the second part of that we have not yet fully embraced and dealt with.

World Asthma Foundation: What would you like researchers to know about the relationship between Staph A and chronic disease?

Rodney Dietert, PhD: I think they need to realize again that the starting point, birth and the first few months, is the time to do something. (In early life) it is easier (to make the most significant changes) and (those actions taken during early development are) likely to be more permanent (as the infant ages). (Also, there is an opportunity to insulate that child from even some problems, maybe diet or otherwise, later in life that (otherwise) could be a risk factor.

That’s the time to do something. Where you get bigger bang for the buck, is early (in life). Researchers simply need to know to look for infectious agents that are involved with conditions like asthma and to start to realize that their management needs to start and stop with the microbes that are protecting the individual, the friendly microbes or microbiota, and to ensure that that is in balance.

If you’re hoping to nudge the immune system in a more useful way, you’re hoping to control inflammation, it’s my contention that if you don’t correct the microbiome, you’re going to be back in the same boat, on the leakyboat, (the) sinking boat, shortly, with your treatments.

There’s sort of a fingerprint of (the) respiratory microbiome, and particularly in the nose, that reflects asthma existing. There’s the chicken or egg question, which comes first, and what’s a result of (what)? Nevertheless, if you don’t actually address that (the respiratory microbiome which affects both risk of Staph A infection and lung immune status) in any meaningful way, then you’ve got to know that the tendency is there that (it is) going to snap back at some point. It’s going to bite you (with an elevated risk of and/or exacerbation of asthma).

WAF will continue to investigate the link between asthma and bacteria.

See also Dr. Dietert’s interview about the Gut and Lung connection.

Rodney Dietert PhD on the topic of Asthma and the bacteria Staphylococcus aureus.

For more information about Dr. Dietert, visit here.

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Asthma and Environmental Fungi – interview with Marie-Claire Arrieta Ph.D.

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

Interview

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.

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Asthma and Microbiome Sharing – Rodney Dietert, Phd

World Asthma Foundation “Defeating Asthma Series uncovers New Hope for Asthma Managementant

Asthmatics: 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 the sixth in a series of interviews with Rodney Dietert, PhD Cornell University Professor Emeritus, Health Scientist Head of Translational Science + Education for SEED and the Author of the Human Super-Organism How the Microbiome is Revolutionizing the Pursuit of a Healthy Life we learn about:

  • Existing evidence clearly demonstrates an association between asthma initiation and the microbiome, both respiratory and gastro-intestinal
  • Regenerative Agriculture is good for the microbiome
  • A diet that is not diverse results in a depleted microbiome
  • People or animals with a depleted microbiome are open to getting some microbiome components from others and the environment around them

Interview

World Asthma Foundation:
Dr. Dietert, Can you talk about a) different types of microbiomes, and b) microbiome sharing?

Video interview: Asthma and Microbiome Sharing – Rodney Dietert, Phd

Dr. Dietert: I’ve had an opportunity to lecture at a couple of different conferences. I’ll mention them if you don’t mind. The Quivira Collection – Regenerative Agriculture Conference in Albuquerque and then the Organic and Natural Health Annual Conference was in Florida. You put those two groups together, again, the regenerative agriculture, farmers, ranchers, and scientists doing things in ways that we never envisioned in terms of integration.

They start with the soil, and they start with animals and insects and how you use them together in an ecosystem to really be productive as a rancher or a farmer but to really support the microbiome of soil, of the plants and the diversity of the plants because those are foodstuffs for their production animals. It turns out the more plants that you may have contributing to the diet, the more robust, in a sense, and diversified the production animal is and the phytonutrients that you will gain through the meat or through the milk or through the eggs from that production animal. It is mind-blowing, it is absolutely mind-blowing.

If you don’t mind just a short story, we have examples of that. You have something like the howler monkey in Vietnam, I believe, eats normally in the wild 57 species of plants. In Vietnamese zoos, they eat maybe 12. I forget the exact number but lower double digits. There are some effects on the microbiome. In the US zoos, they eat one plant species. Guess what’s represented in their microbiome which is a very severely degraded microbiome? Their microbiome becomes humanized with the microbes from the animal handlers.

Actually, the same thing happens in our lab rodents, our lab mice, and our lab rats. They are not like wild mice and rats living out in the wild. They are in a very constrained animal handling setting, and they actually acquire the animal technicians’ microbes to some extent. Investigators working on the immune system, for example, told me, “We were doing these great experiments everything was working and then they didn’t.” Turned out there was a new building built, and they moved their animals over there, or they changed all their staff in the animal facility.

It’s a lesson for us that if you’re in a depleted state, you will pick up microbes from your surroundings. One other point about that that’s interesting is that I talked about non-communicable diseases, NCDs. If I wrote that book now, and I am planning a follow-up book, I wouldn’t use that acronym because a lot of people ask me, they say, “I have asthma or I have Crohn’s. We’re not genetically related but my spouse living in the same household, eating the same food, same air, also developed it later on. Is there any chance these things are actually slightly communicable?” The answer is, more and more, yes, slightly communicable is probably right.

If you get a really depleted microbiome state like you’ve had Lyme disease or something, you have multiple extensive rounds of antibiotics and your household has a microbiome that has — you can argue which came first but — is an asthma microbiome or is a Crohn’s or something, psoriasis, yes, you are open to donation. It could be from your home or hotel room or an airplane but you’re open to something getting in. There are tipping points where there’s some evidence that it’s not like a regular pandemic but to some extent, to say it’s non-communicable is not quite right because we’re sharing microbes all the time.

World Asthma Foundation: Dr. Dietert, we certainly thank you for your time, all that you do for the microbiome and the community. Good afternoon, and thanks again.

Dr. Dietert: Well, and thank you for all you do with the World Asthma foundation, Bill. Pleasure.

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Gut and Lung Connection to Asthma – Rodney Dietert, PhD

In this fifth in a series of interviews with Rodney Dietert PhD, he talks about communication between the gut and lung. Dr. Dietert is Cornell University Professor Emeritus, Health Scientist Head of Translational Science + Education for SEED and the Author of the Human Super-Organism How the Microbiome is Revolutionizing the Pursuit of a Healthy Life we learn about:

* The Gut and lung communication and its relationship to Asthma

World Asthma Foundation “Defeating Asthma Series uncovers New Hope for Asthma Managementant

Asthmatics: 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.

Interview

World Asthma Foundation: Research into the Microbiome and its relationship to health has improved significantly in the last few years. For example, we now know about the relationship between the gut and health. We’ve also learned about communication between the gut and the lung and the impact on Asthma. Dr. Dietert, so there’s some crosstalk, right?

Video interview: Asthma Connection to Gut and Lung Cross Talk – Rodney Dietert, PhD

Dr. Dietert: Tremendous crosstalk, absolutely tremendous. You’re correct that if you’re looking at endpoints, something like risk of asthma or management of asthma, then you really, at a minimum, are going to focus both on the respiratory system microbiome and the gut microbiome. That’s not necessarily the exclusion of others but those two are really important. Just like the gut microbiome can affect the brain, it can affect behavior, mood. You don’t need lots of hardcore meds as an antidepressant when you’ve got the solution sitting right in your gut in terms of the microbiome.

With the respiratory system, you’ve got both the local microbes being extremely important but you have crosstalk, you have chemical interactions that are originating in the gut that are affecting the respiratory system as well.

World Asthma Foundation: Dr. Dietert, we certainly thank you for your time, all that you do for the microbiome and the community. Good afternoon, and thanks again.

Dr. Dietert: Well, and thank you for all you do with the World Asthma foundation, Bill. Pleasure.

To learn more about Dr. Dietert, go here.

Gut and Lung crosstalk interview with Rodney Dietert.
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Can we test for whats in the Microbiome? – Justin L. Sonnenburg PhD

Defeating Asthma Series uncovers New Hope for Asthma Management

In this interview with Justin L. Sonnenburg PhD, Associate Professor of Microbiology and Immunology at Stanford University, we learn about:

* Testing for Microbes within the Microbiome

* That we’re in the early stages of our understanding of the Microbiome

* Research that still needs to be done

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.

“Diseases largely driven by inflammation and an altered immune system. If we start to take our gut microbiota into account, as we live our life, as we make medical decisions, eat different foods and potentially even eventually reintroduce some of these lost microbes, how profound can the impact be on our health?” Justin L. Sonnenburg Ph.D

Interview

World Asthma Foundation:  Dr. Sonnenburg, can we test for what’s in the microbiome?

Video Interview Can we test for whats in the Microbiome? – Justin L. Sonnenburg PhD

Dr. Justin L. Sonnenburg: On an individual level, there are companies that offer testing for the different species to give you the composition of what’s in your microbiome. I can’t speak to the validity of any of these companies, but there are commercial entities out there that will provide a profile for individuals.

World Asthma Foundation:  Thanks. Do you know if it’s specific? For example, research reflects that Bifidobacterium breve and Lactobacillus specifically have been targeted. I’m not a hundred percent sure if it’s inflammation or infection or both, it seems to be successful. The question is, can we test for those specific bacteria?

Dr. Justin L. Sonnenburg: There are targeted tests out there for specific bacteria that where we think given the species may be of interest. Of course, this is most famous for infectious agents. If you want to go in and see if you have Clostridium difficile or salmonella or something like that, there are specific targeted tests. These are less common for the good guys in our gut. I think part of the reason is we still don’t have a great understanding of what the good guys are.

There are studies out there that indicate certain associated with health States are associated with being able to fight off specific problems.

In general, quite often what’s found for one population when surveyed in an independent population doesn’t necessarily hold up.

There’s just extreme variability in the gut microbiome. I think as much as we know about the field is still how fundamental this community is to our health, we’re still at a really early stage of understanding what is healthy and also coming to grips with the fact that there is no single definition of healthy, that healthy really depends on the individual, the context, and many other factors.

World Asthma Foundation: It’s a complex issue and relatively emerging, right?

Dr. Justin L. Sonnenburg:  Exactly. A lot of research still needs to be done.

World Asthma Foundation: Thank you everything that you do on a daily basis for the gut microbiome, certainly for your teachings and your writings and for your time today. Appreciate it.

Dr. Justin L. Sonnenburg: Wonderful being with you. Thanks so much.