Common food dye can trigger inflammatory processes, say university researchers
A recent university study funded by the Canadian Institutes of Health Research reflects that long-term consumption of Allura Red food dye can be a potential trigger of inflammatory bowel diseases (IBDs) and potentially other inflammatory diseases processes as well.
Researchers using experimental animal models of IBD found that continual exposure to Allura Red AC harms gut health and promotes inflammation. Researchers using experimental animal models of IBD found that continual exposure to Allura Red AC harms gut health and promotes inflammation.
‘This further understanding will benefit Asthmatics as well,’ said Alan Gray, Director at the World Asthma Foundation . The human gastrointestinal (GI) tract is home to a diverse ecosystem of microbes, known collectively as the microbiota. Among its many roles, the gut microbiota regulates the immune system and protects against harmful pathogens. In fact, the largest part of the immune system, the gut-associated lymphoid tissue, is found in the gut. This network of immune cells and tissues interacts closely with the gut microbiota, influencing inflammation throughout the body including the lungs.
The dye directly disrupts gut barrier function and increases the production of serotonin, a hormone/neurotransmitter found in the gut, which subsequently alters gut microbiota composition leading to increased susceptibility to colitis.
Khan said Allura Red (also called FD&C Red 40 and Food Red 17), is a common ingredient in candies, soft drinks, dairy products and some cereals. The dye is used to add colour and texture to foodstuffs, often to attract children.
The use of synthetic food dyes such as Allura Red has increased significantly over the last several decades, but there has been little earlier study of these dyes’ effects on gut health. Khan and his team published their findings in Nature Communications. Yun Han (Eric) Kwon, who recently completed PhD in Khan’s laboratory, is first author.
“This study demonstrates significant harmful effects of Allura Red on gut health and identifies gut serotonin as a critical factor mediating these effects. These findings have important implication in the prevention and management of gut inflammation,” said Khan, the study’s senior author, a professor of the Department of Pathology and Molecular Medicine and a principal investigator of Farncombe Family Digestive Health Research Institute.
“What we have found is striking and alarming, as this common synthetic food dye is a possible dietary trigger for IBDs. This research is a significant advance in alerting the public on the potential harms of food dyes that we consume daily,” he said.
“The literature suggests that the consumption of Allura Red also affects certain allergies, immune disorders and behavioural problems in children, such as attention deficit hyperactivity disorder.”
Khan said that IBDs are serious chronic inflammatory conditions of the human bowel that affect millions of people worldwide. While their exact causes are still not fully understood, studies have shown that dysregulated immune responses, genetic factors, gut microbiota imbalances, and environmental factors can trigger these conditions.
In recent years there has been significant progress in identifying susceptibility genes and understanding the role of the immune system and host microbiota in the pathogenesis of IBDs. However, similar advances in defining environmental risk factors have lagged, he said.
Khan said that environmental triggers for IBDs include the typical Western diet, which includes processed fats, red and processed meats, sugar and a lack of fibre. He added that the Western diet and processed food also includes large amounts of various additives and dyes.
He added that the study suggests a link between a commonly used food dye and IBDs and warrants further exploration between food dyes and IBDs at experimental, epidemiological and clinical levels.
On the day after World Asthma Day, May 3, 2022, we scanned the globe to find a statement that best sums up the current state of affairs regarding Asthma.
Kudos to tbe U.S National Institute of Environmental Health NIH Statement on World Asthma Day 2022: Toward Improved Asthma Care
Good enough of summary that we want to publish this in its entirety.
Asthma is a serious lung disease; causes chest tightness, wheezing, and coughing; can often be controlled with proper treatment.
Today (May 3, 2022) on World Asthma Day, the National Institutes of Health reaffirms its commitment to biomedical research aimed at preventing the onset of asthma, understanding its underlying causes, and improving the treatment of it. This chronic airway disease, which is characterized by periodic worsening of inflammation that can make it hard to breathe, affects more than 25 million people in the United States, including more than 5 million children. Left untreated, it can be life-threatening.
While scientists have made substantial progress in understanding asthma diagnosis, management, and treatment, therapies to permanently improve breathing for those who suffer from asthma remain elusive. Researchers around the globe are working steadily toward this goal while they seek to better understand and find new ways to manage the disease. They also are continuing research on the underlying causes of disparities in the incidence, care, and prevention of the disease. On the heels of recently updated management and treatment guidelines, researchers anticipate a brighter future for people living with asthma.
Three NIH institutes primarily support and conduct studies on asthma — the National Heart, Lung, and Blood Institute (NHLBI); the National Institute of Allergy and Infectious Diseases (NIAID); and the National Institute of Environmental Health Sciences (NIEHS). Other NIH Institutes and Centers also support and conduct asthma research. NIH scientists and grantees made important advances in understanding, treating, and managing asthma in 2021, which are briefly highlighted as follows:
Asthma and COVID-19
An NHLBI-funded study showed that during the pandemic, asthma attacks, also known as asthma exacerbations, significantly decreased in a large group of children and adolescents, compared to the year before the pandemic. The study also found that telehealth visits among these patients increased dramatically during this time. The study included nearly 4,000 participants aged 5-17 years with a prior diagnosis of asthma. Researchers believe a better understanding of the factors that contributed to these improved outcomes could lead to better asthma control in all children and adolescents, as researchers noted no racial or ethnic differences in health outcomes in this population.
A NIAID-funded study found that asthma does not increase the risk of becoming infected with SARS-CoV-2, the virus that causes COVID-19. This finding came from a six-month household survey of more than 4,000 children and adults conducted between May 2020 and February 2021.
Asthma Disparities
Researchers have known for decades that social determinants of health – conditions like housing, neighborhood, education, income, and healthcare access – can affect the quality of life and asthma-related health outcomes of people living with the disease. NIH scientists are now reporting new advances in understanding the relationship between social determinants of health and asthma.
Black and Hispanic children who live in low-income urban environments in the United States are at particularly high risk for asthma attacks. These children tend to be underrepresented in large trials of new biologic therapies for asthma.
In a recent NIAID-supported clinical trial, the monoclonal antibody mepolizumab decreased asthma attacks by 27% in Black and Hispanic children and adolescents who have a form of severe asthma, are prone to asthma attacks, and live in low-income urban neighborhoods.
In one study, NHLBI-funded investigators demonstrated the importance of housing interventions in improving the health of children with asthma. Poor quality housing is associated with a high level of asthma triggers – including mold, cockroach, mouse, and dust mite allergens – that can pose a health threat to children with asthma. The study showed the feasibility of using targeted interventions – including better pest management, improved ventilation, and moisture reduction – to achieve healthy housing. It showed that such interventions can result in reduced symptoms and hospitalizations due to asthma.
Environmental Exposures and Asthma
Researchers have known for years that asthma can be triggered by substances in the indoor and outdoor environment. New research shows that exposure to some asthma triggers might even occur before birth.
In an NIH-supported study that included grant support from NIEHS and the NHLBI, researchers reported that prenatal exposure to tiny air pollution particles significantly increased the risk for developing asthma in children. The study, which analyzed data from two different study cohorts, focused on a group of mothers and their children, mostly Black or Hispanic, in the Boston area who lived near major roadways with heavy traffic. It found that more than 18% of the children who were exposed to high levels of these so-called ultrafine particles in the womb developed asthma in their preschool years, compared to 7% of children overall in the United States.
An NIEHS clinical study will assess how environmental factors affect disease progression in non-smoking adults who have moderate or severe asthma. The study will focus on the microbiological and genetic factors associated with atopic asthma, also known as allergic asthma, which is triggered by pollen, dust mites, and other allergens. A better understanding of this data might lead to improved treatments for people with this type of asthma, researchers say.
Climate Change and Asthma
Studies have shown that climate change can increase air pollutants such as ground-level ozone, fine particulates, wildfire smoke, and dust, and that these pollutants can exacerbate asthma. Climate change can also affect the production, distribution, and severity of airborne allergens.
NIEHS, NHLBI, and other NIH institutes and centers are leading the NIH Climate Change and Health Initiative. This is a cross-cutting NIH effort to reduce health threats such as asthma that can develop or worsen because of climate change. The initiative will look at these threats across the lifespan and find ways to build health resilience in individuals, communities, and nations around the world. A strategic framework for the Initiative will help guide NIH investments in this area.
An NIEHS-funded study provides examples of how extreme weather events can affect asthma outcomes. For example, as heat waves and droughts become more frequent and prolonged, the risk of large wildfires will likely increase, resulting in poor air quality that makes it more difficult to control asthma. Other climate-change events can lead to longer and more intense pollen seasons, while mold and dampness in homes may cause asthma to develop or worsen preexisting cases.
About the National Institute of Allergy and Infectious Diseases (NIAID): NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit www.nhlbi.nih.gov. For additional information about NHLBI’s asthma resources, visit https://www.nhlbi.nih.gov/BreatheBetter.
About the National Institute of Environmental Health Sciences (NIEHS): NIEHS supports research to understand the effects of the environment on human health and is part of the National Institutes of Health. For more information on NIEHS or environmental health topics, visit
About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
On this World Asthma Day, May 3, 2002, The Microbiome First – Pathway to Sustainable Healthcare Summit organization committee invites healthcare professionals, non-communicable disease community leaders, and stakeholders to participate in the inaugural Microbiome First Summit, a virtual event taking place online at MicrobiomeFirst.org this May, 17-19, 2022. FREE to participants.
The event, Microbiome First – Pathway to Sustainable Healthcare Summit, kicks off the inaugural event underwritten and moderated by the
World Asthma Foundation (WAF), which is pleased to announce the
following speakers:
Event Keynote RODNEY DIETERT, PHD Cornell University Professor Emeritus Ithaca, NY, USA
Author of The Human Superorganism. Keynote: “Big Picture View of Our Tiny Microbes”
Researcher Sessions MARIE-CLAIRE ARRIETA, PHD
Associate Professor, departments of Physiology, Pharmacology, and Pediatrics, University of Calgary Calgary AB, CANADA Session:“The early-life mycobiome in immune and metabolic development”
JAEYUN SUNG, PHD
Assistant Professor, Microbiome Program, Center for Individualized Medicine, Mayo Clinic. Rochester, MN, USA Session:“A predictive index for health status using species-level gut microbiome profiling”
KATRINE L. WHITESON, PHD
Assistant Professor, Molecular Biology and Biochemistry School of Biological Sciences
Associate Director, UCI Microbiome Initiative Irvine, CA, USA Session:“High-Fiber, Whole-Food Dietary Intervention Alters the Human Gut Microbiome but Not Fecal Short-Chain Fatty Acids”
LISA AZIZ-ZADEH, PHD
Cognitive neuroscientist; Expert in brain imaging, autism, body cognition
Associate Professor in the USC Chan Division of Occupational Science and Occupational Therapy Los Angeles, CA, USA Session: “Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder”
MARTIN KRIEGEL, MD, PHD
Chief of Rheumatology and Clinical Immunology at University Hospital of Münster
GERMANY
Associate Professor Adjunct of Immunobiology at Yale School of Medicine. Session:“Dietary Resistant Starch Effects on Gut Pathobiont Translocation and Systemic Autoimmunity”
ERICA & JUSTIN SONNENBURG, PHD
Senior research scientist and Associate Professor in the Department of Microbiology and Immunology at the Stanford University School of Medicine. Palo Alto, CA, USA Session:“Gut-microbiota-targeted diets modulate human immune status”
EMMA HAMILTON-WILLIAMS, PHD
Associate Professor
Principal Research Fellow
The University of Queensland Diamantina Institute
Faculty of Medicine
The University of Queensland
Translational Research Institute
Woolloongabba, QLD, AUSTRALIA Session:“Metabolite-based Dietary Supplementation in Human Type 1 Diabetes is associated with Microbiota and Immune modulation”
ANDRES CUBILLOS-RUIZ, PHD
Scientist, Wyss Institute of Harvard University and Institute of Medical Engineering and Science at Massachusetts Institute of Technology Cambridge, MA, USA Session:“Protecting the Gut Microbiota from Antibiotics with Engineered Live Biotherapeutics”
EMERAN A MAYER, MD
Gastroenterologist, Neuroscientist, Distinguished Research Professor
Department of Medicine, UCLA David Geffen School of Medicine
Executive Director, G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA
Founding Director, UCLA Brain Gut Microbiome Center. Los Angeles, CA, USA Session: “The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications”
BENOIT CHASSAING, PHD
Principal Investigator, Chassaing Lab
Associate professor, French National Institute of Health and Medical Research. Paris, FRANCE Session:“Ubiquitous food additive and microbiota and intestinal environment”
SEI WON LEE, MD, PHD
Associate Professor
College of Medicine, University of Ulsan
Department of Pulmonary and Critical Care, Asan Medical Center Seoul, KOREA Session: “The Therapeutic Application of Gut-Lung Axis in Chronic Respiratory Disease”
PATRICIA MACCHIAVERNI, PHD
Clinical and translational researcher
Research Fellow, The University of Western Australia Perth, WA, AUSTRALIA
Honorary Research Associate, Telethon Kids Institute. Session: “House Dust Mite Shedding in Human Milk: a Neglected Cause of Allergy Susceptibility?”
LIEKE VAN DEN ELSEN, PHD
Research Fellow, The University of Western Australia, Australia
Honorary Research Associate, Telethon Kids Institute. Perth, WA, AUSTRALIA Session:“Gut Microbiota by Breastfeeding: The Gateway to Allergy Prevention”
PAUL TURNER, PHD
Rachel Carson Professor of Ecology and Evolutionary Biology, Yale University
Microbiology faculty member, Yale School of Medicine. New Haven, CT, USA Session:“New Yale Center to Advance Phage Research, Understanding, Treatments, Training, Education”
ANDRES CUBILLOS- RUIZ, PHD
Scientist, Wyss Institute of Harvard University and Institute of Medical Engineering and Science of Massachusetts Institute of Technology MIT
Boston, MA, USA Session: “Protecting the Gut Microbiota from Antibiotics with Engineered Live Biotherapeutics”
CLAUDIA S. MILLER, MD, MS
Emeritus Professor,Allergy/Immunology and Environmental Health University of Texas San Antonio, TX, USA Session: “Toxicant-Induced Lost of Tolerance for Chemicals, Foods and Drugs: a Global Phenomenon”
Media Supporter Content TONI HARTMAN
PRINCIPAL
Microbiome Courses
London, England UK Session “Educating Parents About ‘Seeding And Feeding’ A Baby’s Microbiome”
Summit Details:
The goal of the Microbiome First – Sustainable Healthcare Summit is to
improve quality of life at reduced cost by addressing the microbiome
first, as recent research shows that all of these non-communicable diseases have a relationship to the microbiome.
65% drop in serious asthma cases due to mask-wearing Israeli hospital reports
The Times of Israel reports that the Sheba Medical, an Israeli hospital reports 65% drop in serious asthma cases due to mask-wearing.
Here’s the 411 according to published reports:
• A study conducted by Sheba Medical Center found that the past year saw a 65 percent drop in serious asthma cases that required hospitalization.
• The drop was credited to widespread mask-wearing during the COVID-19 pandemic, which also helped decrease the spread of viruses such as the flu in the past year.
• By wearing masks, people are also less likely to suffer from seasonal allergies, as face coverings prevent pollen from flowers, trees, and grass coming into contact with the nose and mouth.
• The report follows Israel’s decision to drop the requirement to wear masks outdoors.
Israeli hospital reports 65% drop in serious asthma cases due to mask-wearing Jerusalemites wearing face masks walk in Jerusalem on February 04, 2021.
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.
Dr. Nikolaos Papadopoulos reports on bacteriophage research.
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.
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.
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.
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, Rodney Dietert PhD
For additional information on Asthma and Staphylococcus aureus and the WAF defeating Asthma Project, visit:
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.
