Episode 36: Is the gut microbiome the key to allergic diseases?
Could we cure allergies by taking probiotics or transplanting the gut microbiome from a healthy person? What does all this mean for eczema/allergy prevention? To find out, join our conversation with Dr. Rima Rachid, allergist and immunologist at Harvard Children’s Hospital, and Meenal Lele, eczema mom and author of Baby and the Biome. We discuss the promising trials with fecal microbiota transplants for food allergic children as well as the best probiotic to take for eczema and when it’s important to take it. (And if you like our podcast, consider supporting it with a tax deductible donation). Read the transcript.
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[00:00:00] Lynita: Hello. My name is Lynita and I'm an eczema parent and podcast manager for Global Parents for Eczema Research. Today we are talking about food allergies. Eczema and food allergies often go hand in hand and there is good research to show that food proteins on damaged eczema skin can be a fast track to food allergies. I'm joined by Meenal Lele from Philadelphia. She is the mother of two boys One with food allergies and author of the book, The Baby and the Biome, released last year.
I'm also joined by allergist and immunologist, Dr. Rima Rachid. She is Associate Professor of Pediatrics at Harvard Medical School and Director of the Allergen Immunotherapy, Allergy and Asthma Program at Boston's Children's Hospital. Dr. Rachid and Meenal, welcome to the podcast.
[00:01:19] Meenal: Thank you so much for having us.
[00:01:20] Dr. Rachid: Thank you very much.
[00:01:22] Lynita: Meenal. Can you please tell me about your experience with food allergies?
[00:01:26] Meenal: Sure, we had been told food allergies are a genetic disorder and nobody else in our family on either side had any of these issues. And so we were very upset to find out when our first son started developing these issues. As I continue to do research and realize that he had eczema early, he had the colic, he had showed all the signs of early gut disruption and the information was out there and I think that's really what was frustrating for me personally is I've been in the medical space on the industry side for the last 20 years. And, it was reading the New England Journal of Medicine and finding out that his food allergies were potentially preventable. And then I started reading the Journal of Allergy and Clinical Immunology and saying like, wait a minute, we have a sense of where these are coming from and we're not doing anything about it? I wanted people to know that what they could do from a preventative perspective and doctors like Dr. Rashid and many others had already sort of clarified that there's a lot we could do from a preventative perspective to start to decrease our risk.
Again, nothing is guaranteed, but we can do a lot to prevent these diseases and I wish that I had known that.
And, and so it's been sort of my mission over the last 10 years to help, um, educate the community about what we can do.
[00:02:35] Lynita: Knowing what you do know now, what would you have done differently?
[00:02:38] Meenal: First off, when my son was very young,and he started to develop signs of eczema, right? I wish I had understood how much that is a hallmark. He was definitely spitting up way more than he should. So I wish we had seen that as an early sign of some gut distress. I wish we had seen the eczema as an early sign of what all the listeners here know as the atopic march.
And, of course, now we know very well. About early allergen introduction and what we can do to introduce these allergens early and train the immune system. So uh, our children don't develop food allergies. And what's interesting about early allergen introduction is that it seems to work in today's modern context, But it also doesn't get to the root of the problem, right? Why are these diseases here in a way that they weren't a generation ago?
Why is it that I grew up knowing nobody with food allergies? And you know, if you dig into the research, it's clear. That what's happening is this barrier dysfunction and this massive shift in people's microbe,, the infant microbiome from age zero to three, as our immune system is laying down and figuring out what to do with itself, this microbial disruption really matters. I'm not the researcher, right? I'm reading other people's research, And it's not clear in the research exactly what we can do. Although, again, Dr. Rachid is working on that to fix it.
[00:03:58] Lynita: Dr. Rachid, is there anything you want to add to that,
[00:04:01] Dr. Rachid: Well, there is really no known single introduction that definitely will prevent an allergic disease. When it comes to early introduction we found that early introduction of peanut in patients with, significant eczema or with egg allergy led to a significant decrease in the incidence of peanut allergy at the age of five years. But then in Australia, when they implemented these changes and re-evaluated the incidence of peanut allergy after three or four years, they found that there was nothing significantly different. But then when they looked deeply into the data, they found that actually there was a subset of patients who were Caucasian and received a very large dose of peanuts, which was like 10 peanuts per day, and if introduced early in life that could prevent peanut allergy from developing. Now, whether or not this is applicable to other populations, other races, we don't really know for sure. It could be very much also affected by the environment, by the culture. It's a very complex issue.
[00:05:03] Meenal: And I think that opens up a whole other question, which is, what's the right move? Because when they tell parents, introduce peanuts early, or eggs, or whatever else, the way most people interpret that is, At some point, when my child is a baby, once or twice in that window, I will give them some eggs. But that is not what the study showed. The studies were doing things every single week for months at a time. And then you saw this reduction, right? And so that presents its own whole host of challenges. But if you're not going to do that, I don't think it's fair then to expect the benefit,
[00:05:37] Dr. Rachid: Yes. And I was nodding. Yes, absolutely. You're absolutely right. The real world is very different. So it is as if there was like a window. I mean, I really feel like this is just. Personal observation right now. This is not science, but as if there is a window, a window where if you stop or if you are not very adamant about giving peanut on a regular basis, then a reaction will happen. So there is no doubt that there was a striking difference in the LEAP study when peanut was introduced early but the problem is that we have to yet understand in each society and in each country or culture, how does that translate when it comes to real world applicability and what happens? How much are we able to prevent of peanut allergy?
[00:06:28] Meenal: Sure. And that window, that magic window for each baby was different. We just know that it happens sometime between like four months and roughly 11months.
[00:06:36] Dr. Rachid: And sometimes later, you're absolutely right.
[00:06:38] Meenal: The idea is that you want to start the early allergen introduction before that window and keep going through the window. And the way I like it is like you put the baby gates up before you think your baby's going to crawl and you keep them up until after the baby has mastered stairs, right? And that day of crawling is totally different for every baby.
[00:06:58] Dr. Rachid: And that is the fascinating part, but also the frustrating part. That's what we need to learn more and understand more.
[00:07:05] Meenal: Some of the things we can do are try and minimize some of the unnecessary disruption, right? So the biggest things being, like, if you can breastfeed, that's great. If you can minimize unnecessary bathing of the baby… This is one of the biggest things is constantly stripping the infant skin with really harsh, unnecessary, infant soaps. And then being judicious with antibiotics in cooperation with your pediatrician, because nobody wants an infant who's sick but I think there's a lot of times we, as parents, want to jump to the antibiotics. Or times where we introduce antibiotics unnecessarily in foods, in soaps in our house, things like that. So, if we can let our pediatricians know, hey, we want what's overall best for our kids in
their long term health, that's an opportunity the pediatrician has to say, is this a watch and wait situation? Or is this a, nope, they need these antibiotics you know?? So, the book, The Baby and the Biome tries to go through this. How do you make these decisions and these trade offs? Because nothing, nothing is 100%. It's all about how can you make choices that cumulatively, reduce the risk of microbial disruption and barrier dysfunction.
[00:08:17] Lynita: You've done your research well, by the sounds of it,
[00:08:20] Dr. Rachid: I definitely see your point about the antibiotics, you know, but I just want to emphasize that it's very important. I mean, these are babies and babies are very susceptible because the immune system is not well developed. I'm not just an allergist, I'm an immunologist. So we do know that the immune system of the baby, the first year is not well developed. So that is why specifically the first two months of life, we are very careful and any fever for us is alarming.
And that is why we give antibiotics because we're worried about, you know, serious infection. So yes, as you mentioned, you really have to consult and discuss with the pediatrician. I certainly would not put the pressure on the pediatrician not to administer an antibiotic because we know so many patients who actually developed allergies without antibiotic intake.
[00:09:06] Meenal: Absolutely.
[00:09:07] Dr. Rachid: And I'll tell you we didn't really find that an antibiotic makes a big difference. in microbiome, but again, I do think that you need very large studies to answer this question.
[00:09:17] Meenal: Right, and I think that's really important. I want the listeners to know how vigorously I was nodding. So, any unnecessary use of antibiotics is what you're trying to avoid.
[00:09:27] Dr. Rachid: I agree completely. I think that always, at the end, a medical decision has to be taken carefully. I wish I could tell a parent this is what you need to do in order to prevent food allergy. But apart from telling the mom to eat as healthy as possible, apart from recommending breastfeeding, although we know breastfeeding will decrease the incidence of wheezing, but not necessarily food allergy, but in general, because it's healthy overall. Apart from attempting early introduction and see how it goes. I mean you know it's hard, there is a big question. Yes I'm very biased. I do believe the microbiome plays a major role. This is why we're working so much on it. And there is a lot of data about it, but I do not think necessarily it's the
only factor.
There could be also other factors. For example, the type of processed food we're having, et cetera. I do agree wholeheartedly with the idea of avoiding. bacterial soap as much as possible.
So how much can you control that is questionable.
[00:10:26] Lynita: Thank you both for that really good summary. A little comment you made Dr. Rachid. About, I wish I could tell parents exactly what to do. We wish you could too. Um, this is so nice that we can talk about why we can't just give you a straight answer. So, that brings me to probiotics. Probiotics are supposed to help restore the balance in our gut microbiome and Meenal, I believe you did do a research summary about probiotics in the gut.
[00:10:54] Meenal: Yeah that particular meta analysis was about eczema prevention, specifically with the use of probiotics. What's particularly interesting about probiotics is that we're very challenged in what we can safely grow. But your standard probiotic almost, to a T, they are things that happen to grow in milk. And they happen to do it in a way that can be somewhat aseptic. And that is just a very limited set of things. So we're starting with very, very limited tools.
So the eczema one, though, I think is pretty exciting. Lactobacillus rhamnosus was the only bacteria that seemed to have some effect, about a 50 percent reduction in the risk of atopic eczema. But I should point out that what that meta analysis showed is that L. rhamnosus can cut the risk of atopic eczema, only that, and only when used perinatally, when mom takes it in the third trimester and baby takes it in the first few months during breastfeeding. And so I think in a family that has a strong history of eczema and they're worried about it, that's an intervention that might make sense.
[00:11:58] Dr. Rachid: It's so hard to evaluate the studies because you have different races, different ethnicities, different diets. Diet is so important in the microbiome, right? It is very, very, very complex. So I would say, if you feel like you want to give a probiotic to your baby, you can go ahead. I mean, these are over the counter. But let us also remember that there could be benefit, but occasionally it could be harmful. Usually in a healthy infant, it's not going to be horribly harmful, but the FDA has issued a warning about administering this in a preterm baby.
[00:12:32] Meenal: Obviously Dr. Rashid is correct on all these things, and I hope that that was what people took away from what I was saying, too.
[00:12:40] Lynita: The frustrating thing is you're both right. It's so complex. Um, but I do feel like we are making progress and one of the things Dr Rachid, that you're really working on right now is fecal microbiota transplant, where you take the healthy gut microbiome from a person and you share that with someone who might have an unbalanced microbiome in their gut. How did you come to this idea? And and where is it leading at the moment?
[00:13:08] Dr. Rachid: Sure. So, I always like to say that when I came to the US in 1998 to do my fellowship in allergy immunology, it was really because I had very strong interest in primary immunodeficiency, I trained at the American University of Beirut between 95 to 98, and it was a major referral center. And we saw all types of diseases with all the spectrums of it.
And I only saw one case of food allergy at that time. So when I came in 98, I was shocked. All I saw in clinic was allergic diseases and food allergies. I mean, initially I was like, this belief, like, is this even real? But it was, it was real. The patients were reacting and my interest really shifted to understanding this epidemics because there was an epidemics that was happening.
And we know now that food allergy have increased significantly over the past 20 years. So we decided to study the gut microbiota of babies with and without food allergies. So we collected stools from babies that were food allergic. And we enrolled them between the age of one month to 12 months, and we followed them for three years. And what we found was that there was significant differences in the gut microbiome between babies that were food allergic and babies that were healthy and that continued to diverge over time.
So we selected few bacterias and we put them into a highly allergic uh, mouse model and we found that select bacterias can actually completely prevent anaphylaxis in a food allergy mouse model that is highly allergic. So these bacterias are very interesting, but they were not available to be evaluated in humans. But what was available was fecal microbiota transplantation. So what is a fecal transplant is, as you mentioned, it is a transfer of uh, somebody's stool and that person should be healthy into a person that has a certain condition or disease with the hope that this is gonna treat that condition or disease.
We took the fecal material of babies that were healthy. and fecal materials of babies that were food allergic, and we put them separately into the food allergy mouse model, and we found that the fecal transplant from healthy babies actually protected anaphylaxis on these mouse.
So why was it so exciting for us? Because that was in 2015 when fecal microbiota transplantation get administered via a capsule that was odorless and tasteless showed very similar efficacy to a fecal transplant that was administered via enema or via colonoscopy.
It was really when the frozen encapsulated fecal material that was administered and showed similar efficacy that we're like, okay, now we should evaluate this in food allergy because enema or colonoscopy is a bit too aggressive for somebody who has a food allergy, but is otherwise, you know, fine. But with the capsules being available, and they are odorless and tasteless, we decided that we're going to do a fecal transplant trial to evaluate patients with peanut allergy. But with food allergy, there is one caveat, what if the donor ate a food that a patient is allergic to? So the donors are very carefully selected. Because they have to be very healthy.
[00:16:31] Dr. Rachid: Our primary end point was, is it safe? And we found that actually overall it's safe. We administered the first 10 fecal transplants without pre-treating with antibiotics. So all the patients had to react during a food challenge, to hundred milligram peanut protein or less. That's less than half a peanut. And then we looked whether a patient could react to 300 or 600 milligram one month, or four months after the fecal transplant. And we had three patients. who actually showed efficacy.
So we were like, so what happens if we were to give antibiotics?
So we enrolled five patients and they received antibiotic pre-treatment. And then we did again a fecal transplant. And four months later. three out of five reach 600 milligram when they reacted. So that was very, very promising. We also had very interesting immunological results that the markers of tolerance increase and the markers of allergies decreased in these patients. What was interesting is when we took the stools of the patients at baseline And then put them into the food uh, allergy mouse model, there was no protection from anaphylaxis, but when we took the stools four months later, there was complete protection from anaphylaxis that did not happen with those who didn't respond. There was no protection. So there was like, was another evidence that it's the change in the microbiome that led to protection from anaphylaxis in these mice.
So with these very promising results, we decided to go into phase two. And this is a very concentrated form of fecal transplant, it contains less than 1% fecal material. And the good news is that you can leave it in the fridge. So once the children who are 12 to 17 take the capsules, they will go home. They will take capsules for 28 days of therapy. And then we will do another challenge at one month and four months and see what happens. But this is where we are. We are at phase two trials right now. I think it's very exciting, I think we're still scratching the tip of the iceberg when it comes to understanding the microbiome and how these interventions are going to help. But at least what's very exciting is that the studies are ongoing.
[00:18:37] Lynita: That's very exciting, and your results are really impressive.
[00:18:40] Dr. Rachid: Promising.
[00:18:40] Lynita: And I love that you are including teenagers in your Phase 2 trial, so you're working with kids that have already got food allergies.
[00:18:50] Dr. Rachid: Yes.
[00:18:50] Lynita: Do you think down the track there might be potential for this to be a preventative option?
[00:18:56] Dr. Rachid: Yes. yes, I do think so. but you know, we have to do first the trials to understand more the microbiome. We know from many food allergy studies that children seem to respond better to interventions than adults.
But when it comes to prevention, yes, it is certainly on our mind. The other thing is, it's possible we might be able to detect specific bacterias that seem to be more associated with success and, and with efficacy, and it's possible potentially that one could develop uh, second generation, of probiotics. They have to be evaluated really in robust clinical trials and they have to be done rigorously to answer the question. Is this helpful? Is this not? And if it's helpful, which patients are benefiting?
[00:19:40] Lynita: Fantastic. Thank you so much for sharing about your research.
[00:19:43] Meenal: I think that's super exciting, but I think we're all searching for the answers and we'll take, take them where we can get them. And and honestly, it would be so amazing to finally understand what's actually going on, right? Like, what are the key species? Is there a window in which they matter most? I hope the answer isn't forever: it's complicated and we don't know.
[00:20:02] Lynita: Me too.
[00:20:03] Dr. Rachid: I don't think the answer is going to be forever: it's complicated and we don't know, because there's also the development of artificial intelligence and our understanding of the microbiome as it changes. So I do think that we'll be able to understand and analyze data in a much faster way and complex way than we are currently able to.
So in the next five years, I think we will look at it in a very different way. And we will have to learn more and understand more to see the variability and how we take this in context when people eat differently and have a different environment.
So it is complex. It is fascinating, this is the work of so many people at Boston Children's, our collaborators in Minnesota, with Alex Khoruts, or Eric Alm at MIT, or Libby Hohmann, who was a pioneer in doing the oral transplantation uh, Talal Chatila and, and his lab. And Robert Boisker and everybody. So it takes more than a village. It takes a city.
[00:20:59] Lynita: Yes.
[00:21:01] Meenal: If there's one thing I think we should take away from just how much work your team and everyone you're working with has to do to fix it, is that. We should be careful with it in the first place, right?
[00:21:12] Dr. Rachid: Yeah, that's why it's critical to find that window and the signature of tolerance when patients lose some of their allergies. It's critical and we're hoping to evaluate that further. Yeah, Absolutely.
[00:21:22] Lynita: fantastic. Thank you both so much. We are at time but I have very much enjoyed this conversation.
[00:21:29] Meenal: Thank you so much.
[00:21:30] Dr. Rachid: Thank you.
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