Defeating Asthma Series uncovers New Hope for Asthma Management
In this 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 H. pylori and Asthma connection
- That H. pylori was disappearing with modernization
- Can we identify these missing microbes
- Can we replace them?
- Can we repopulate these missing microbes?
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.
Dr. Blaser: These are good questions.
World Asthma Foundation: Great. Thank you for the support.
Dr. Blaser: Fine. That’s good. I’m happy to help you because this is what I really believe.
World Asthma Foundation: Doctor Blaser, what prompted your interest in this area?
Dr. Blaser: Well, it all starts with H. pylori. We did a lot of work on H. pylori. Some of this is in the book, but we developed the first really good blood test to tell if a person had H. pylori or not, and that opened a lot of doors for us.
We made the association between H. pylori and stomach cancer, and brought depth to the association with ulcers. We’ve discovered a form of H. pylori that has a gene called CagA.
We discovered that actually using my own serum and tests, and so we could distinguish between two different subtypes of H. pylori, one which is more interactive with people, and the other is less interactive. The more interactive is called the CagA-positive strain.
And we learned that H. pylori was disappearing with modernization. To many doctors, that was good news because of the linkage with stomach cancer and ulcers, but I was not certain.
I’m not a gastroenterologist, my specialty is infectious diseases, but I had a lot of gastroenterologists working with me. One day I said to one of the gastroenterologists, Dr. Richard Peek, “I’ve heard a lot about this disease called reflux or GERD. Why don’t we see whether there’s an association with H. pylori or not? I’m thinking that there might be because GERD is a disease that is increasing in incidence.”
It was a disease that wasn’t recognized until the 1930s, it wasn’t in the medical literature until the 1930s.
We did the study, it’s recounted in Missing Microbes. He came back to me and said, “This is funny. There’s an inverse association. People who have GERD less often have H. pylori than others.”
Then it occurred to me that maybe H. pylori is protective against GERD, and maybe the reason that GERD is going up is because H. pylori is disappearing.
We conducted about 10 other studies on GERD, on Barrett’s esophagus, on adenocarcinoma of the esophagus, all of these showed an inverse association. It became clear to me that helicobacter is bad for your stomach but good for your esophagus.
Because I’m a medical doctor, I knew that there’s a relationship between reflux and asthma. There are people who start wheezing and their doctor treats them with a medicine to suppress gastric acidity and their asthma gets better. That’s well-known to physicians, and in adult-onset asthma, that might be 10% of the cases. It’s not rare.
I thought, “Well, if helicobacter protects against reflux, maybe it protects against asthma.” Of course, I knew that asthma was one of these increasing diseases, increasing as H. pylori was going away, so it was a reasonable hypothesis.
At that point, I was at Vanderbilt University. I tried to get the pulmonary people interested in this idea to test it. There was some interest but nobody had the time to test it, and then I moved to NYU, and I became the chair of medicine at NYU. The people at NYU were more responsive.
There was one physician there who had a big asthma clinic, and I said, “Let’s do this test. You give me serum from people who have asthma and controls who do not have asthma, send it to us blindly, and we will see, is there any relationship with H. pylori.”
They did that, and actually I recount this in the book Missing Microbes because it’s one of the more dramatic moments in my career.
My colleague Joan Reibman writes to me, and she says, “You’re right. There’s an inverse association between H. pylori and asthma.” She said, “The results aren’t that great. Maybe we should discuss it.”
They come to my office, she and a couple of other colleagues, and she starts showing me the data. I said, “Oh, that’s it.” The odds ratio was 0.7, I remember it, which is an inverse association. It was statistically significant because there were several hundred people. The study had about 500 people.
I said, “Oh, that’s nice. Well, what about CagA?” She said, “Oh, we didn’t run CagA. We didn’t analyze it.” I said, “Oh, CagA is the most important because that’s the one that’s the most interactive, and what we found with esophageal disease is that CagA strains are the most protective strains.
They are the ones most associated with stomach cancer and ulcers (and thus most bad), but for esophageal disease, they’re the most beneficial strains. They’re the ones that are most protective.
How’s that possible that they are both most good and most bad? It’s because they’re the most interactive. The other ones are not nearly as interactive. And good or bad depends on context, the disease in which you are studying.
I said to her, “Well, what about the CagA strains in asthma?” One of the people on her team was a statistician, he had his laptop, and he said, “Oh, I can just calculate this right now.” He taps a couple of keys in his computer. He says, “Odds ratio of 0.6.” It was even stronger. This was a blinded study.
That was the first study to show an inverse association of H. pylori and asthma. Then about a couple of weeks later, a new epidemiologist came to NYU, Dr. Yu Chen, and she said, “I’ve been told to look you up because you were doing interesting work.” And I said, “Well, I’m really interested in asthma.”
There’s a series of big national studies called the NHANES studies. I suggested to her that we should look at asthma in NHANES because we had a contract some years earlier and we ran H. pylori serology on 11,000 people as part of NHANES.
“So why don’t you go to the NHANES database and find those 11,000 people and see if there’s any relationship with H. pylori?” She did it, and what she found is yes, same thing, inverse relationship with asthma, almost exactly the results from New York.
So we have two independent blinded studies, one with 500 people and one with 11,000 people, both show the same thing.
What was interesting is that we could divide asthma into two classes: childhood-onset asthma, and adult-onset asthma. The association is that in general, the correlation was not with adult-onset asthma, it was only with childhood-onset asthma.
There were several NHANES studies and they had conducted H. pylori serology in another one. We performed that study as well, and we’ve found almost the same results.
Three large independent blinded studies all show the same thing. What was clear is the lack of H. pylori is a marker for risk of asthma for childhood-onset, really clear. Others have been working on this, but I think these were the three most definitive studies.
Then a very good scientist in Zurich, Anne Müeller began doing mouse experiments. There’s a way that you can provoke asthma in mice. There are different mouse models of asthma in mice.
She asked, what if she gives H. pylori to these mice, can she protect them against asthma? And she could.
Then she worked out many of the details of the mechanism, how H. pylori is involved in a lot of the regulation of immunity in the model that I just mentioned. The mechanism is there.
In the meantime, I’ve been working extensively with Dr. Müller for the last four or five years to continue this work. We’ve got a couple of papers already published, and we have more papers that we’re working on and about to submit about the microbiome and about H. pylori. Some of the effect of microbes in asthma is H. pylori.