Defeating Asthma Series uncovers New Hope for Asthma Management
In this second interview with Martin J Blaser MD, Director of the Center for Advanced Biotechnology and Medicine at Rutgers Biomedical and Health Sciences and the Henry Rutgers Chair of the Human Microbiome and Professor of Medicine and Microbiology at the Rutgers Robert Wood Johnson Medical School in New Jersey and the Author of the “Missing Microbes – How the Overuse of Antibiotics is Fueling Our Modern Plagues.” we learn:
- About the connection between Asthma and the Microbiome
- About research and studies that predict Asthma in childhood
- About bacteria not just in the stomach but in the colon
- About C-sections and the likelihood to develop asthma
- About the Mayo Clinic study on Asthma and antibiotics useage
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.
World Asthma Foundation: Dr. Blaser, can you help us connect Asthma and the Microbiome?
Dr. Blaser: I’ve gotten very involved in studying the human microbiome in general, not just in the stomach, but in the colon. We and others are working on the relationship of the bacteria (microbiome) in the colon and asthma.
Again, there’s a paper that’s published. A young doctor from Denmark, Dr. Jakob Stokholm, came to work in my lab. This happened after Missing Microbes was published, so it’s not in the book. He’s part of a study in Copenhagen called the COPSAC study, the Copenhagen Open Study of Asthma in Children. They have cohorts of moms whose kids are going to have high risk of asthma, either because they have asthma or they already have a child who has asthma.
In 2010, if I remember correctly, they enrolled 750 moms with this high risk. They obtained fecal samples from the moms. They also got samples from the kids at one week, one month, and one year of life. Then they followed these kids until they were about six. The question was, is there anything that might predict who was going to get asthma at the age of six? We did a lot of work studying the microbiome in their fecal specimens, and what we found is consistent with what other people found: that the microbiome matures over time between one week and one month, and one year. It shows a pattern of maturation, but in some kids, their microbiome doesn’t mature in the normal way.
Then we made a very important observation. In those kids whose microbiome didn’t mature normally when you compare them to kids who did have normal maturation, the odds ratio, the chances that they were going to get asthma when they were six was 3, (300%) meaning a rate three times normal. Then we divided those kids by whether their mother previously had asthma or not. If their mother didn’t have asthma, the maturation pattern did not make a difference, but if their mother did have asthma, the odds ratio was 13.
We’re getting in the range of the association between smoking and lung cancer. That’s how strong that is. That was published about two years ago in Nature Communications. We have a new paper that now is in press. It is about cesarean sections. It’s known that kids born by C-section have a higher risk of developing asthma. The question is why?
From this study, again with the children in the Copenhagen study, we confirmed that kids born by C-section are more likely to develop asthma than those who didn’t. In those kids who had C-section, on average, their microbiome early was abnormal compared to those who were born vaginally. But by a year, in many of them, their microbiome had matured normally, but if it didn’t mature normally, those kids had a very high rate of getting asthma. Again, a high risk. That’s going to be published within a month or two because it’s been accepted already.
Now, what I will tell you is that with Dr. Müeller and with a graduate student in my lab, Tim Borbet, we’ve been doing a lot of mouse-asthma studies where we can experimentally give a mouse asthma or allergy. We already can show that if we perturb the microbiome early in life with antibiotics, they’re going to get more allergy and more asthma. That’s interesting because a paper was just published from British Columbia, showing that they had a really good program to diminish antibiotic use across the whole province. They showed that with diminishing antibiotic use, asthma rates are going down, so it’s all connected.
Furthermore, I’m part of another study that’s also in press. It’s going to be published probably in a month or two with scientists at the Mayo Clinic. I visited there a few years ago. The Mayo clinic is located in Olmsted County, Minnesota. It’s a pretty isolated place. In general, people don’t come, people don’t go, they stay there. It’s a very good stable population to study. I suggested to my colleagues there, why don’t you look at the effects of antibiotics in early life for certain marker diseases, including asthma and food allergy, and atopic dermatitis and allergic rhinitis. All these diseases go together. The group there is very active and outstanding, and they studied about 14,000 kids who were born in Olmsted County, and they were followed up to the time that they were 15 or 14. They had a lot of information from their health records because most of their medical care there is through the Mayo Clinic.
The bottom line is that if they received antibiotics in the first two years of life, their odds ratio of getting asthma was 2. They were twice as likely as kids who did not receive early-life antibiotics. Lots of things are pointing to the importance of the early life microbiome and the importance of when its being perturbed by antibiotics, that there’s increased risk. The relationship with moms, that’s this kind of transgenerational thing that each generation is stepping down.
World Asthma Foundation: A lot of these antibiotics are not only prescribed, but they’re ubiquitous in our diet and our food supply right?.
Dr. Blaser: Yes. Well, I’m very interested in that as well, although the prescribed antibiotic is more important because it’s higher dose. In mice, when we give low doses of antibiotics, it perturbs the immune system but not so much. When we give them the same kind of doses that kids get to treat their ear infections or their throat infections, it really perturbs their immune system and puts it on a different path. That’s also published.