Is your gut making hay fever, seasonal allergies, eczema and food intolerances worse? Here are 5 ways to fight back with Prof. Adam Fox

Allergies have tripled. Hay fever, eczema and food allergies now affect millions of people. But why are allergy symptoms getting worse, and what does gut health have to do with it?

In this episode, Adam Fox, a world-leading allergy professor at King’s College London, explains why allergies may be rising so fast, why many beliefs about allergies are wrong, and what new science reveals about your immune system, skin, and gut.

Professor Fox explores why some foods are more likely to trigger reactions, and why modern allergy science is increasingly focused on gut health. Adam also discusses why 90% of people told they are allergic to certain things may not actually be allergic, the difference between allergies and intolerances, and why some antihistamines may be doing you more harm than you realize.

If allergies barely existed a few hundred years ago, what changed? And could your gut now be shaping the way your immune system reacts to the world around you?

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Actionable Takeaways

Have food allergies actually increased, or are we just noticing them more?
They’ve genuinely increased. Best estimates suggest around 5% (about 1 in 20) of children in the UK and US have a food allergy, and severe reactions needing emergency care have risen substantially over recent decades, especially in younger children.

Should I treat hay fever like a minor nuisance?
Not really. It can affect sleep and focus. Start with non‑drowsy antihistamines and/or a steroid nasal spray, avoid sedating antihistamines, and if symptoms still disrupt daily life, ask about immunotherapy.

Why can skin contact with foods raise allergy risk in babies?
If a baby first encounters a food by eating it, the gut immune system is more likely to learn “this is safe.” But with eczema, the skin barrier is weaker, so food residues can enter through inflamed skin, and the immune system may mistakenly learn that the food is a threat, making an allergy more likely.

What should I do if I suspect an allergy?
Keep a quick record of what you ate/exposed to, how fast symptoms started, and what happened (hives, swelling, wheeze, dizziness). Take it to a clinician. Diagnosis works best with the combination of your story plus the right tests.

If I think I’m allergic to penicillin, should I just avoid it forever?
Not automatically. Penicillin allergy is often over-labeled: about 10% of people carry the label, but when properly assessed, around 90% turn out not to be truly allergic. It’s worth discussing assessment and de-labeling rather than carrying the label for life.

Transcript

Jonathan: Adam, are people born with food allergies?

Adam: No.

Jonathan: Can you develop a food allergy as an adult even if you've eaten that food your entire life?

Adam: Yes.

Jonathan: Were our hunter-gatherer ancestors allergic to pollen?

Adam: No.

Jonathan: Do most people who think they have a penicillin allergy really have one?

Adam: No.

Jonathan: Are allergies and food intolerances the same thing?

Adam: Definitely no.

Jonathan: And finally, what's the most common misconception about allergies?

Adam: I think it's that allergies are trivial because for some people they are actually life-defining.

Jonathan: Now, my sense is that allergies are getting increasingly common. When I was young, I'd never even heard of a peanut allergy, and now my daughter can't take a peanut butter sandwich to school. And I think intolerances are the same. So this is sort of a transformation in terms of the world we're in compared to the one when I was a child. That's my impression. But actually, have food allergies increased overall, and how common are they now in, you know, the US and the UK?

Adam: It's a really, really good question, and you're absolutely right regarding your impression because when I was at school, 1980s, I was at school with fifteen hundred kids, and there was one child who had a peanut allergy, and everyone knew about it because it was such a strange thing that this child would have a terrible reaction if he went near a peanut. And it's desperately sad because that young man went on, he got a job in the Far East, spent some time in Hong Kong, and on his way home, he had a fatal anaphylaxis to peanuts. Now, my son went to the same school that I did. We still live in the same area, and he was thirty years below me, and I probably by the time he left knew about a quarter of his class professionally. As the local allergy doctor, I was seeing these kids, and there are a lot of them. And I knew from my son's friends when, you know, when they were coming over to play that a number of them would present us with their EpiPens when they arrived and, you know, used to have delighted parents when they discovered that Ethan's dad was an allergy doctor because they could really relax a lot more. So clearly, something significant changed in terms of disease patterns over the course of those thirty years, and that's reflected in the data. If you gather a lot of studies together, we can sensibly estimate that around five percent of children in the UK, US, for example, will have a food allergy. Now, you can also look at patterns over time, and there's nice data actually from the UK from National Health Service primary care databases that show that between 1998 and 2018, so a twenty-year period, there was a trebling in the number of people presenting to emergency departments with severe allergic reactions. So this is a very significant increase. Year on year, six or seven percent to get to those sorts of amounts. And if you dig in to, well, why is that happening? Is it adults having allergic reactions to penicillin, or is it teenagers with latex allergy? It's not. It's younger children with food allergy that's driving that increase. And if you then look at other robust data that looks at the general practice reporting of food allergy amongst patients. We can see that in the 10 years between 2008 and 2018, and then data sort of drops off because of COVID, that really impacted the ability to collect reliable data, there was a doubling of food allergy during that period reported. So we've seen really significant changes, and then if you just go back 100 or 200 years into Lancet papers, it's pretty clear that if there was mention of allergy, it was pretty unusual. Whereas of course, today it's not.

Jonathan: The thing that springs into my mind is peanuts. Yeah, when I think about peanut allergy, and maybe that's partly because you can't take peanut butter to school, and so that focuses the mind. But how much of this is an allergy to peanuts within this food allergy, or is that just the thing that springs to my mind and yeah, there's a couple of I'm being a bit mean on the peanut?

Adam: No, you're not. There's a couple of reasons why peanut seems to get all the headlines. So firstly, it is a really important allergen. About one in 50 kids in the UK, 2%, we think, have a peanut allergy. It's amongst a relatively select group of foods that do account for most food allergies. So milk allergy, egg allergy, peanuts, tree nuts, sesame, wheat, and kiwi. A relatively small number of foods in the bigger scheme of things account for the overwhelming majority of food allergies that we see. But peanuts have often been used as the model in research studies because it's serious; you don't grow out of it, unlike milk and egg allergies, which you commonly do. So it's been a real focus of academic attention. But then, it is also responsible for some of the fatal anaphylactic reactions that happen. But interestingly, it's not the most common cause of fatal anaphylaxis, certainly not in younger children, because milk is the most common cause in younger children.

Jonathan: Did you just say that the most common cause of like serious allergy is milk?

Adam: The most common cause of fatal anaphylaxis, the most common cause of anaphylaxis in younger children is milk. It's not peanuts. Now, a couple of reasons. So firstly, milk allergy in younger children is much more common than peanut allergy, but most of it is outgrown. So amongst an adult population, you're gonna find more persistent allergy from childhood to things like peanuts and tree nuts and sesame because you uncommonly grow out of those maybe 10, 20%. Whereas with milk allergy, 80% of children with milk allergy will outgrow it and won't be allergic in adulthood or later childhood.

Jonathan: I wanna come back to that, but we were just talking about peanuts and I'm so curious. You said there has been this big rise. It is a really important part of the allergy. Is this true everywhere around the globe?

Adam: No. So what you become allergic to really does relate to what's being eaten in the household that you're brought up in. And you see this, it's fascinating. You see this in the very diverse populations that we see in a central London teaching hospital, so where I work. And you will notice slightly different patterns of disease amongst different communities. So for example, in India, chickpeas, lentils are much more common allergens than things like peanuts. And amongst British Asian families, if they've got a nut allergy, it's more commonly gonna be something like cashew, pistachio, walnuts than it is to be peanut, and that just reflects what's being eaten in the household. Amongst Middle Eastern families, if you look at rates of allergy in Israel, for example, sesame is a really important allergen, and that's because a lot of families eat hummus. So where you go, what's being eaten will influence what you're likely to see causing allergies in children.

Jonathan: I might have thought I'd be allergic to the things I've never been exposed to, but you're saying actually I'm allergic to the things that I grow up with.

Adam: As we have developed a better understanding of how you become allergic in the first place, it sort of makes sense that it's gonna be the things that you grow up with. Not just anything, it's gonna be the things that are particularly good at inducing allergic responses, and there's certain foods that seem to be very good at inducing allergic responses, and they're typically things that are sort of quite sticky and have proteins that, for sometimes reasons we don't really understand, are particularly good at upsetting our immune system. But a great example of that would be peanut, but another good example would be sesame. So often both of them are eaten in forms that are quite sticky, so peanut butter, hummus, for example. And what I mean by sticky is they get around, so you're likely to find residue of that food not just around your mouth, but on your hands, on surfaces. And because our understanding of how you become allergic has evolved and now we understand that it's all about early infancy, problems with your skin barrier, so the presence of eczema, and exposure through the skin barrier to those sticky, potentially allergenic proteins. So I guess what I'm trying to say is if you're a baby with eczema and you've got siblings or parents that have eaten hummus or peanut butter and they're kissing or touching that baby, and that baby's immune system, through the disrupted skin barrier because of the eczema, gets to see those proteins and doesn't know what they are because the infant has never eaten that food before, that's when they're at risk of developing allergy.

Jonathan: You're saying we tend to develop this when you're a very small child, correct, and that what's happening is actually my immune system is getting exposed to, you know, this peanut or this sesame through something that sort of gets stuck onto the skin, like peanut butter or hummus, possibly through someone else in the family kissing me on the arm or my older brother whacking me, whatever it is. And then somehow it's getting in because the skin barrier hasn't blocked it out, and my immune system is like, "Hang on, this is something bad. Red alert."

Adam: Yeah. Let's develop an inappropriate immune response, because that's what allergy is, an inappropriate immune response to something that should be ignored. So it all comes down to where that immunological signal is received. Because if, as an infant, that child, eczema or no eczema, the first time they come across peanut or sesame, eats it, then the part of their immune system that sees it is the gut immune system, which is primed to acknowledge that anything it sees in the gut is most likely food, so can be ignored, and there's no need to develop an immune response. And so the next time you eat that food, no problem. Whereas your skin immune system is thinking very differently because your skin is designed and expected to be covered by the skin barrier, which is meant to provide an impervious wall between itself and the outside world. And its immune system is ready that if anything gets past that impervious wall, so you've got a cut in your skin and germs or bugs get through, your immune system is there ready to kill whatever it is that it finds and ideally adapt to recognize what those things are so it can kill it even more effectively next time round. But if what it's seeing are actually harmless things because your skin barrier isn't working properly, it's not an impervious wall, it's a leaky barrier, because genetically you don't have the glue that sticks your skin cells together, then there is a risk that your immune system will see things it's not designed to see and make bad decisions because it doesn't have context. It doesn't know that that food protein that sat on your skin barrier is food because that infant has never eaten it before.

Jonathan: Why is the skin not keeping these things out?

Adam: Well, because there is skin barrier dysfunction, which is a fancy way of saying that your skin barrier isn't working as well as it should. You don't have to spend long in an allergy clinic, certainly when you're seeing younger children, for it to be really clear that there is a relationship between eczema and food allergies. So it's from the probably, say, 20% of children we see who have eczema, it's from that population that we see the overwhelming majority of food allergy developing. And the worse your eczema is and the earlier your eczema starts, the more likely you are to see food allergies and more food allergies.

Jonathan: And Adam, what is eczema?

Adam: So eczema is an itchy, dry skin condition that for many people is mild and just gets better as they get older. For some, it can be much more severe and persistent, and it's characterized by inflammation in the skin and a disrupted skin barrier. So essentially what that means is that your top layer of skin, instead of tightly sticking together and keeping all the moisture and good things in and all the germs and bugs and bad things out, instead, because of that leakiness, water is lost from the skin, and that means your skin gets dry. And those things sat on the outside of your skin, germs and bugs and things, wind up the immune system that sat just underneath that top layer of your skin and cause inflammation, so you get inflammatory components as well. And that combination, that leakiness and that inflammation, creates an environment where things can go a little bit skewwhiff from an immunological perspective. I remember when I started, especially, there was so much debate about whether this was genetically programmed. Was this an allergic condition itself? But we've sort of moved past that because, helpfully, somebody found the gene for eczema. So we now know that there are genes that produce something called filaggrin, which is like the sticky cement stuff that sticks that top layer of skin cells together. And if you've got one not quite effective copy of that gene and you're not producing enough of the gluey stuff to stick your skin cells together, or you're producing enough of it but it's not as sticky as it should be, then your skin barrier will not be that impervious wall. It will be leaky, and that's where you might get eczema. If you've got two copies that aren't quite working of that gene, then you're more likely to have more severe and persistent eczema.

Jonathan: And if I don't have eczema, does that mean I'm never gonna develop an allergy?

Adam: You're much less likely to, but we do see people, not commonly, who don't really report any eczema in early childhood who still go on to get food allergies and certainly other allergies as well later.

Jonathan: We talked a lot so far about food allergies, but the other allergy that I think is really prevalent is hay fever or seasonal allergies as it's called in a lot of the rest of the world. Is that a similar story? Has that also been increasing? You said at the beginning that you didn't think our hunter-gatherer ancestors were sort of sniffling while walking across the African savanna.

Adam: Yeah, you can sort of dig into antiquity and find occasional cases of things that sound like they were probably allergy. I think one of the Roman emperors, Britannicus, supposedly didn't lead his army into battle because he was allergic to horses. Who knows what the real story was? But I think if you wanna get a clear sense of change over time, there was a pediatrician in Manchester called Bostock in the early 19th century. He had seasonal allergies. He recognized the relationship between his blocked up, itchy, runny nose and itchy eyes and the pollen season. And so he set about finding other people so that he could send a letter to The Lancet to describe hay fever, and it took him nine years to find another 28 cases. He was either extraordinarily antisocial or there just weren't many people around who suffered from the same problem. Now, whenever I tell this story when I'm giving a talk, I'll ask the audience to stick their hand up, "Do you have hay fever?" And it will typically be between 20 and 30% of the adult population. So something has happened, and you can't put this down to genetics because we are talking about, you know, no more than a 200-year period where this has gone from being, I guess, a medical curiosity to something that is the blight of a significant proportion of people's summers.

Jonathan: And so when did it start to increase and go from, like vanishingly rare to you're now saying 20 to 30% of all adults?

Adam: Yeah, I think you can probably start looking in the post-war period when we started to see more asthma, more hay fever, more eczema. So there's reasonably good data looking at different centers and different time points to suggest that there was a big increase, you know, through the '60s, '70s, '80s to sort of modern-day levels, whereas the food allergy surge appears to have happened after that. This does seem to be more of a post-war phenomena.

Jonathan: I think a lot of people have quite mild allergic responses to the pollen. Like a little bit of an irritation. Is this like a sort of impactful issue for some people?

Adam: It absolutely is. So I think this is one of the challenges that allergy has in terms of PR. We all know people who have got relatively mild hay fever because there's a huge number of them around, and if they just take, as I said to certain family members, "If you just took your antihistamines, you'd be fine," and they would be. But amongst the people who suffer from nasal allergies, for example, there is a 15, 20% group where these are really significant and they have a genuine impact on their not just quality of life, but real difference on their outcomes. So for example, if you're a 16-year-old in the UK, given that we have the highest rates of hay fever and nasal allergies probably in the world, it does seem a little strange that all of our major public exams are set right in the middle of the grass pollen season, which is the most common allergen to drive hay fever. In the UK, people will do their practice exams in the Christmas period when of course there's no pollen around, and they'll then have the actual exams in May and June when pollen levels are particularly high. And if you have hay fever, one study demonstrated that you were 50% more likely to drop a grade from your mocks to your actual exams than somebody who didn't have hay fever.

Jonathan: I guess it would be the same for being at work in the summer versus the winter.

Adam: So you look at productivity and it has an impact on that. You're much more likely to be off sick because of your hay fever. It affects your reflexes when driving, and it's been shown that if you've got significant hay fever and you're taking certainly sedating antihistamines, which many people are still recommended to take, which is a big no-no, you shouldn't. But if they're taking them, their driving reflexes will be equivalent to somebody who's on the limit drink-driving-wise for alcohol. So, you know, for people with proper hay fever, it's a real problem, and if you've got grass and tree pollen allergy, that can mean that almost six months of your year are meaningfully affected by this problem.

Jonathan: I'm thinking that the Americans calling this seasonal allergies are actually right, and this term we use in the UK, hay fever, which is a very strange phrase since I've never seen any hay and there's no fever. You're saying almost takes away how serious it might be for people who've got sort of more extreme responses to it.

Adam: I think absolutely, yeah. So it's easy to consider it something trivial. But from a material minority, it's far from trivial.

Jonathan: I'd love to come back to the other allergy that we talked about in the quick-fire at the beginning, which is one I've had some personal experience with, which is I have been told in the past by doctors that I was allergic to penicillin. But you said right at the beginning that basically most people who think they have a penicillin allergy don't.

Adam: Yeah. It's monumentally over-diagnosed, and the reason is when you ask somebody who has that label of penicillin allergy, and give you a bit of context, about 10% of UK people will have that label somewhere on their medical notes. They've been told, "Don't have penicillin. You're allergic to it." And we've replicated that. In fact, very soon after I started my job at the Evelina London Children's Hospital in 2006, one of the first studies we did was exactly that audit. We audited everybody coming in as an inpatient to the hospital, and literally bang on 10% of children were already labeled as being penicillin allergic.

Jonathan: And would this be similar across the West as well?

Adam: Yeah, absolutely, and very similar studies from Europe, from the US, from Australia, very, very similar. And then when you ask people, "Where did this come from? Why have you been told to avoid it?" The story is almost invariably the same. It's, "When I was little," which means it's a third-hand story because the individual can't remember it themselves. "When I was little, I wasn't well. I was given antibiotics. I came out in a rash," and somebody put two and two together and said, "You've come out in a rash because of the penicillin," when in fact we all know that small children with infections often get rashes. So huge potential for overdiagnosis, and that's compounded by the fact that there aren't relatively easy allergy tests that you can do that would just confirm it. So essentially, you get told you're allergic based just on the story, and it never gets challenged. So you go through the rest of your life always being given second-line antibiotics, often which are both more expensive and unpleasant. So typically, in a UK primary care, that means you'll be given something called erythromycin, which is way more likely to make you sick. It's horrible. You're more likely when you show up in an emergency department with a nasty infection for there to be delay in you getting the right antibiotics, because people can't give you the normal first-lines because the normal first-line antibiotics are either penicillins or cousins of penicillin, where we know there's a chance of cross-reactivity. And this label holds for the whole of your life, so there's 90-year-olds with all sorts of issues being given different antibiotics because of something that's based on the most spurious of evidence from 88 years earlier.

Jonathan: So how many people do you think actually are allergic to penicillin?

Adam: Well, I can go further than think, because the studies where you get a group of people who have been diagnosed and actually do the correct testing and do the definitive test, which is a challenge, you give them penicillin to see what happens, pretty universally across British, American, Australian, European studies, 90% of the people labeled turn out not to be allergic. Now, it still remains tricky to what we call de-label those people because you have to be able to engage with them. The only reliable test is bringing them in and giving them some penicillin in a safe environment.

Jonathan: Now if you were allergic to penicillin, say you're doing it with an adult, someone saying, "Well, what would you expect to see happen?"

Adam: So quite quickly after being given the dose, you'd expect their body to be releasing histamine and other mediators of inflammation, which will cause itchiness and hives and swelling, and for most it will be mild, but in a small proportion it could potentially be anaphylaxis, so a potentially life-threatening serious allergic reaction. Hence, you can't just say to people, "Nah, you'll probably be fine and you're not allergic, so just do it," because you'll get it wrong one out of ten times. So they need a history taking from somebody that knows the right sort of questions to ask and often you can't get much sense back because they'll say, "This was forty years ago. I have no idea." You know, if it's a recent thing, I can ask things like, "Was it the first time the child's ever had antibiotics?" Because we know that you need to develop a sensitivity first before you can react next time round. So classically, if the story is, "My child had penicillin antibiotics once, was fine, but immediately after the first dose of the second course, they came out in hives and an allergic reaction," I'll be saying, "Okay, that's a good story and I'm not gonna bring you in to try it because chances are you are allergic." But when, as it usually is, my child's actually had three courses of antibiotics, halfway through a course of another different antibiotic, they got a bit of a rash that lasted for a few days and continued even after they'd stopped the antibiotics and actually has had a different penicillin derivative on another occasion and been absolutely fine, that kid needs a very brief sit in your waiting room, have some penicillin de-label.

Jonathan: So Adam, if you're listening to this and you've been told you're allergic to penicillin or you know somebody who is, what should you do?

Adam: I think firstly, find out what your origin story is. That often means speaking to your parents, because chances are this label appeared when you were too young to remember it yourself. And find out whether it fits with that likely narrative of, "I was a small child, wasn't well, was given antibiotics, came out in a rash," and that was it. And then speak to your GP about whether it's worth getting a further assessment. Now, in some areas, there are really, really good services being developed to help de-label because it makes sense on a population level to get past this. In others, it's gonna be harder work to find somebody to support you doing that. But you should definitely be raising it because it doesn't suit anybody, your healthcare provider or you, to be mislabeled.

Jonathan: We sort of covered a lot of different allergies here, and one thing I'm struck by is that across all of them, you've talked about this really big rise, whether that was your example of going to school and it was, like, one kid who had a peanut allergy, and now it's, like, a quarter of the school, or the fact that two hundred years ago you couldn't find somebody who had these seasonal hay fever allergies. What's changed?

Adam: So the prevailing theory for many years was the hygiene hypothesis, or also known as the clean child theory, which is one of these theories that's absolutely entered the public consciousness and is very hard to shake. But actually, it's got huge holes in it. So the idea is that there was a birth order effect that was noticed in the 1980s by an epidemiologist called Strachan, and he observed that the older child in the family seemed more likely to have allergies than younger children. And the explanation for this was, well, in, you know, given modern living and the difference between how we live now from, you know, a hundred or two hundred years earlier and the lack of threats from different microbes that there is these days, that that first child had relatively little pressure on their immune system to develop quickly, and consequently, the immature immune system would develop inappropriate responses. It basically needed to find some sort of trouble, and because it couldn't find cholera or typhoid or anything really nasty to direct itself at, you got these inappropriate allergic responses. Whereas the younger children in the family were brought into an environment where they had older siblings bringing all the bugs and germs that they got back from nursery, so much earlier in their life, their immune system was forced to mature because it was exposed to more, and that more rapidly maturing immune system was less likely to then go on and develop allergies. But big holes in that. So firstly, large birth cohort studies, whilst some of them showed that effect, not all of them. It was absent in other places. And over time, it simply became apparent that that was an overly simplistic view. If you now look, and recently actually, just in the last few months, there's been a meta-analysis, a huge study pulling together lots of different studies looking at what are the underlying risk factors for having food allergy, for example. And it shows a load of things, and this is looking at hundreds of studies that cover millions of patients. And there's themes to the risk factors. There's genetic things, so having a family history puts you more at risk of getting allergies, so clearly there is a genetic component to this. Then there's things like the eczema story that we talked about, so the presence of eczema and other allergic conditions. And then there's the really interesting ones that start pointing pretty clearly towards a microbial story as well around exposures. There are now increasingly studies showing that there is a difference between the gut bacteria, the microbiome, and in fact not just the gut bacteria, but skin bacteria, nasal bacteria, because you have microbiomes not just in your gut, but on your skin, in your respiratory tract, that there are differences between allergic children and children who don't get allergies. Now, I don't think we've really nailed it down, because we're absolutely in our infancy of our understanding around this relationship between our microbiome and allergies, is whether people who have a tendency to allergies therefore have a certain type of gut bacteria, or whether having a certain type of gut bacteria leads to you getting allergies. That's really hard to disentangle, and it's gonna take a long time to do that. But then, of course, as you'll know, you know, anyone in this space knows this is such an almost overwhelmingly complex area because we're not just talking about a diverse microbiome or a less diverse microbiome, the idea that there's a binary. If you've got a more diverse group of bacteria colonizing your gut, then yes, that does seem to be associated with a less allergic profile, whereas having a less diverse microbiome and profile does seem to make you more likely to have allergies. There's so many different types of bacteria that are all producing lots of different things, all of which interact with each other. Trying to disentangle this is hugely complicated. And if you look at the league tables for allergic disease, it's very striking that at the top are Australia, New Zealand, Canada, UK, US. Geographically very disparate places, but culturally very similar places. And I always challenge anyone that says, you know, "No, no, I really believe in the hygiene hypothesis." And it's like, well, what about Switzerland? You know? Where is somewhere that has got really low infant mortality rates, that has got really low rates of infection and those sorts of issues amongst their childhood population, why are they not up there in terms of allergy? Because they're not. They're sitting somewhere in the middle in terms of prevalence rates. So I think what we can confidently say is that this is complex and multifactorial. There's certainly a genetic component. Of course there is, because we know there are allergic families. There's certainly really important specifics. For example, the presence of eczema making you more likely to get food allergies. And I think we can also be very confident that the microbiome plays a really, really important role. But I think the real challenge is, and the real question here is, so how can you then leverage that to make less people allergic or to make the people that are allergic less allergic?

Jonathan: Before we move on, why are you so confident the microbiome plays an important role?

Adam: Because consistently you find that there's differences between people with allergies and without allergies. And our improved understanding at an immunological level of how our immune system develops tolerance is clearly highly dependent on the environment in your gut and elsewhere that is hugely informed by which bugs are present. Try and give a very, very quick example. If you go to mouse models, so sort of in the lab with mice, you cannot induce tolerance in mice who are brought up in completely sterile environments. So ones where they have no microbiomes and no gut colonization of bacteria, you can't get those mice to be okay with foods. They react to everything.

Jonathan: They're basically sort of allergic or intolerant to everything?

Adam: Yeah. They're over hyperreactive in terms of their responses to things, whereas regular mice that do have a gut bacteria, if you feed them allergenic foods very early, they'll develop tolerance to them. Whereas if you rub those foods into their skin, into abraded skin, you can make them allergic to it, going back to what we talked about earlier with the food allergies.

Jonathan: And so what you're saying is you've got these two mice, one with microbes and one without. And the ones with microbes can end up eating peanut butter. But if you haven't got the microbes, you're never going to be able to eat the peanut butter.

Adam: That's right. Yeah. So essentially, we need the right sort of gut bacteria to develop an appropriate relationship with the outside world. And actually, more recent research is suggesting actually that your siblings are really important here, and that might explain a degree of birth order effect, that if you've got lots of friendly bacteria and lots of children, you bring another small child into that environment, they'll often share those bacteria, and that can help develop a healthier microbiome for that younger child and maybe protect them from allergies. So when you start viewing things through the lens of the microbiome, a number of things start falling into place. But if, you know, to then go back and push back the other way, I was involved in a study a few years ago where we got hundreds of infants. This was across the world, hundreds of infants who had milk allergy, and if their mother wasn't able to breastfeed, they'd be put onto these hypoallergenic formulas. And they were randomized to either getting one that had pre and probiotics in and the other one that didn't. And we showed that if you got the one with pre and probiotics in, it would give you a healthier, in inverted commas, a more diverse, with the right sort of bugs, microbiome, but it just didn't make any difference to the outcomes. We were hoping to show that if you gave the right bugs to the right children with milk allergies, they would outgrow their milk allergy faster, be less likely to get other allergic diseases. Just didn't make any difference. So understanding it, but then knowing how we can influence it in a way that's gonna improve outcomes. Two very, very different questions.

Jonathan: That's fascinating, and I think if I'm playing it back, what you're saying, Adam, is we know that the microbiome is really important in terms of ensuring that we don't have these allergies. We don't yet know exactly what you need to have, but what we do know is that somehow it's not the situation we had, you know, 100 years ago because you said there has been this explosion in all of these allergies.

Adam: Yeah, so many different factors. Yeah. And another little interesting bit of evidence, recent studies looking at dietary diversity in moms and in infants as well in terms of the risk of food allergy turns out to be important, and there's now really, really clear evidence that moms who have a broader and more diverse diet with all sort of healthy different food groups and with a child who then also is introduced to more foods early and a breadth of foods, we see less allergies developing.

Jonathan: I'm conscious that we haven't really clarified the difference between, like, an allergy, a sensitivity, and an intolerance, and these words are thrown around a lot. Could you help me to understand that?

Adam: Sure. They are very different things. The terminology's really important. But the bottom line is that an allergy does involve your immune system, an intolerance doesn't involve your immune system. Now, the most common food intolerance is lactose intolerance. It's really common. We have a gene that allows us to produce something called lactase, which is the enzyme in our gut that breaks down lactose, which is the sugar in milk. And if you don't have enough of it, then when you have lactose, say you have a glass of milk, then the sugar can't be broken down properly, and that means that you create a lot of gas in your gut and basically become farty and bloaty, and you get an upset tummy for 20 minutes afterwards. And that can happen transiently when you're younger if you get an infection in your gut, because the infection causes inflammation in the lining of the gut, which is where that lactase enzyme is stored. It's eroded away because of the infection, and it takes sometimes up to a month or so to recover. So you can have a viral gastroenteritis, get diarrhea and vomiting for two or three days, and then find that you feel better. But when you go back to your normal diet, you're still getting really loose poos and stomach cramps and bloating. And that's because you've eroded away your supply of lactase. You can't break the lactose down. Whereas if you switch to lactose-free food, you'll be absolutely fine. And then within the month, things go back to normal. And that's very common in early childhood. But then genetically, most people in the world are programmed to not bother to produce that lactase enzyme beyond childhood because of course, once you don't need your mother's milk anymore, we're not really designed to drink the milk of other species. That's a slightly bizarre thing to be doing. But then there's a group of people who have a mutation in that gene, which means that they don't stop producing the enzyme. They continue to produce it throughout adulthood, so they can break down lactose throughout their lives, and that's most Northern Europeans, whereas most Asians and Africans, there are interesting exceptions dotted around, but most can't tolerate it. Hence, you'll see the difference in diet. When you look at the diet of an adult Chinese person in China, there's not any lactose-containing food because nearly everybody is lactose intolerant, whereas in Western Europe, we've developed a very lactose-heavy, dairy-heavy diet because we're fine with lactose. So that's intolerance. It's not dangerous. It's unpleasant, and there's a range of other intolerances that fall into different categories, but none of them are dangerous, and none of them involve your immune system, and that's in stark contrast to allergies. And when it comes to food allergies, it's your immune system that's the problem. So your immune system has produced allergic antibodies that recognize that food, so then the next time you eat it, they will spot that you've eaten that food and trigger a reaction, which is usually mild but can be catastrophic, so it's potentially dangerous. And this is one of the reasons why food allergy is so challenging as a condition to manage because fatal anaphylaxis, thankfully, is very, very rare, even amongst allergic populations.

Jonathan: Adam, you've used that word anaphylaxis a few times. Otherwise, I have no idea what it means.

Adam: Okay. So anaphylaxis is a serious allergic reaction that is potentially life-threatening. Now, a common definition would be that it's an allergic reaction that involves either your breathing, so airway or breathing are affected, or your blood circulation. So you could have a persistent cough or wheeze, or if your blood pressure drops, you might feel lightheaded, dizzy, you might collapse. Any of those symptoms, that means this is the real deal. This needs to be taken seriously. You require adrenaline as quickly as possible injected intramuscularly into your muscle in order to make you better. And whilst most people will recover without treatment, there is a small chance that without that adrenaline treatment, things will get worse, and you could potentially die from it, so it's a medical emergency.

Jonathan: I'm reminded of the question I asked at the very beginning, where I said, "Do all allergies happen in childhood?" And you said, "No." And I would say at a personal level, I do have these seasonal allergies, this hay fever fairly seriously now, and I don't remember having it at all until I was an adult.

Adam: Yeah. In an adult allergy clinic, there's much more of a respiratory focus, so it's much more around asthma and severe allergic rhinitis, seasonal allergies. But there are also the children who grew up and still have their food allergies. And then there are a cohort, a small cohort of older people who will develop food allergies as they get older. And they can be broadly divided into two sorts. Now, actually, the largest group are people who have what we call cross-reactivities. So they've got hay fever, really common, and give you a good example, birch is their problem, so they're allergic to birch pollen, one of the more common pollens to be allergic to. There are many fruits and vegetables that contain in them, often close to the skin of the fruit and vegetable, that looks pretty much identical to birch pollen. And when they eat that food in the raw form, they'll get a little tingly reaction, and it can be quite unpleasant, but it's very, very rarely dangerous in any way. So anaphylaxis from what we call pollen food syndrome, that cross-reactivity, is really uncommon. But it will sometimes stop them from eating foods, and sometimes the range of foods can be really large, so all stone fruits and a load of vegetables and nuts, and it can really interfere with your day-to-day diet. But it's not seen as a dangerous allergy. So it needs diagnosing and it needs counseling to support people to help manage it, and one of the important things is that the protein that looks very similar to pollen that you find in foods is really unstable, which means it breaks down very quickly as soon as it's in your mouth, which is why it doesn't cause severe reactions. And it only requires a little bit of processing, such as cooking or heating, to break it down. So the classic person with pollen food syndrome will say, "I've got hay fever. I used to eat apples all the time. Now I've noticed that when I have a raw apple, it gives me a real tingle. But if I have apple pie or apple juice that's been pasteurized, I'm absolutely fine." And that will be a really classic story. So there's that group that's common, but they're less of a worry than the smaller group of people who will say, "I've eaten fish all of my life, no problem, and suddenly I had a mouthful of cod and I had an anaphylaxis as a consequence." So they develop from nowhere, and we see it more commonly with fish and shellfish, to things they've previously been absolutely fine with, and then they have an allergy that is potentially dangerous and they have to carefully avoid it.

Jonathan: And do we know why that's happened?

Adam: Sometimes an immunological event can lead to a loss of tolerance. So sometimes there's an illness that somehow during that, something happens in your immune system, means that something that used to be fine suddenly isn't recognized in the same way by your immune system. And often you'll get that in the story, but of course, it's always hard to be certain that that's the real cause. And it's incredibly frustrating because they've often thought that they've dodged the bullet completely, and suddenly it appears from nowhere.

Jonathan: Can we talk about gluten? Sure. Because that hasn't come up. And that I think is maybe the one sort of allergen that I hear about all the time, and where I understand, you know, there are people who are genuinely allergic to it, but then there's a much broader set of people who are worrying about it as an intolerance. What's the reality there?

Adam: Well, the really important thing is to clarify the difference between allergy to wheat or gluten and celiac disease, which is a different type of disease. It's often classed as an autoimmune disease, where there is a specific hypersensitivity, so oversensitivity to wheat, but not in the way that you would get with a typical allergic reaction. So you do get people with genuine wheat allergy who, like somebody with a peanut allergy, when they eat wheat or gluten-containing foods, they will come out in hives and itchiness immediately. But then there's also the not uncommon condition of celiac disease. So people who, when they have gluten, whether it's in wheat or rye or barley in their diet, it will cause an inflammation in their gut that will make them unwell, but in a more chronic way. And if it's not diagnosed and gluten isn't excluded, they're at risk of developing lymphomas, like serious medical issues in the longer term. Whereas if they exclude it from their diet, they'll feel an awful lot better. And often there's quite significant delay in the diagnosis, and it will often not present itself till a little bit later in life. So those are two quite distinct and, in a medical sense, very easy to identify groups because there are highly specific tests that will confirm you have this problem. But those are both completely distinct from people who simply say, "I feel better when I exclude gluten from my diet, and when I include gluten in my diet, I feel unwell," whether it's because they feel tired or nauseous or bloated or a whole range of different symptoms. And if that is genuinely reproducible... And, you know, we need to have an open conversation. It needs exclusion to confirm it gets better and reintroduction to confirm that it really gets worse, and testing to confirm that they don't have celiac disease. And then we would refer to, a bit of a mouthful, as having non-celiac gluten hypersensitivity. They genuinely and reproducibly feel less well when they have it, but they don't have celiac disease, which means they could choose to continue to have it and it wouldn't be dangerous, but they'll have the consequences of not feeling as well. And that's a very poorly defined group, and we've got a lot of work to do to understand that group better. And it's human nature, isn't it? Everybody wants the silver bullet. I don't feel great. I don't feel at my best. I'm tired all the time. And it's probably because you're barely sleeping, you're working really hard, you have a lot of coffee and alcohol, you have a very poor diet. So that's probably the answer to that. But it's really appealing to think, "Oh, if I just cut gluten out of my diet, I'll feel a lot better." Now, nutritional scientists will always tell you that whatever your dietary change you make, there's usually a bit of a honeymoon period where you briefly feel better just because you're taking control of what you're doing and looking more carefully at your health, but then often revert back to where you were. And you'll often hear that story. People will take something out of their diet, find that transiently they do feel better, but then realize actually soon enough everything's broadly the same. But there are certain foods, and gluten's definitely one of them, where as a consequence of eliminating that, you're actually having much broader impact on your diet, and it could be that that's being helpful rather than the gluten specifically.

Jonathan: So if someone listening to this thinks they have an allergy, what should they do?

Adam: So if you're concerned about a food allergy specifically, there is actually... In the UK, there's national guidance that if you go to your GP, they are obliged to sort of ask the right sort of questions to understand what type of allergy you might be describing, organizing appropriate tests, and referring you as appropriate, and it's really important to do that. We know, and this is pretty shocking to myself and colleagues, only around 10% of people with food allergy in the UK ever see anyone beyond their GP about their food allergy.

Jonathan: So that's sort of like family doctor?

Adam: Exactly, their family doctor. There are now a range of treatment options for food allergies that weren't around five or 10 years ago. So it's actually really important if you have food allergy to get good advice because there are options that will really change outcomes.

Jonathan: Now, I've seen ads for, like, a blood test, and you can take a blood test, and it will just tell you the answer of what you're allergic to. So is that what you end up-

Adam: Definitely not. The only way you can get a proper diagnosis is a combination of a proper allergy-focused clinical history together with the appropriate tests. Allergy tests are terrible screening tests, and getting a correct diagnosis is super important because avoiding foods you're not allergic to is a waste of everybody's time and makes life much more difficult, and not avoiding foods that you are allergic to is potentially dangerous. There are two validated allergy tests. One is a skin prick test, which essentially looks at your immune system's response to being directly exposed to either the food or environmental allergens. So if you wanna diagnose seasonal allergies or food allergies, it's a really useful test together with a good clinical history. And there's also blood testing that looks and measures the amount of allergic antibody specific to a particular food or environmental allergen. Those are also helpful, and sometimes even all of those together doesn't quite give you enough, and we'll do the definitive test, which is what we call a provocation challenge, where if the test is saying you might be allergic to peanuts and you've never eaten it before, the only way to find out is bring you in somewhere safe and giving you some peanuts to eat because then if you are allergic, you'll react. And if you aren't allergic, you won't react, but if you do react, you're somewhere that we can deal with that reaction. We'll only do this to kids or adults when they're already well, because you're more likely to have a bad reaction if you're unwell. We give them small increasing doses so they only react to the smallest amount they're sensitive to, and we immediately treat reaction as soon as it happens. So consequently, the overwhelming majority of these food challenges lead to minor reactions that get treated immediately. But even if there is an anaphylaxis, often it's in the form of somebody saying, "Oh, I'm feeling itching. I'm coughing persistently," and we'll just use adrenaline and that settles things down very quickly. So as long as it's done in the right way by the right people and at the right time, it's a very, very safe test and it gives you a definitive answer.

Jonathan: You've played a big role in developing something new that's called desensitization. Can you explain what that is and how it works?

Adam: So this is a paradigm shift really in the way that we manage food allergies, and it's not a new concept. In fact, the first recorded case, 1908 in London, where a child with anaphylaxis to egg was given small but increasing amounts of egg to make them less sensitive. And it's the same principle that we use for pollen and dust mite allergies, where we give people either injections or tablets under the tongue of small but increasing amounts of the allergen to make them less sensitive, to retrain the immune system to not react at such a small amount. And it works really, really well for food allergy, particularly in younger children. So we'll do it in kids all the way up to 18 and there are some places where they'll do this in adults as well. But when you do this in younger children where their immune systems are more what we call plastic, so basically more malleable and more open to suggestion, you can really shift somebody from being sensitive to a tiny amount and at risk of having bad reactions, to being able to tolerate a large and sometimes not just a large amount, but actually be able to eat it freely, which is the real prize. When we do this in younger children with peanut allergies, for example, not always, but sometimes we'll get to the point that they can freely eat peanut without needing emergency medication around, and that's night and day from where we were 10, 15 years ago.

Jonathan: And can you do this at home yourself?

Adam: Definitely not. It needs careful, close supervision because there is a risk associated with doing the treatment and it's only suitable for certain patients. It needs a lot of what we call shared decision-making with parents as to whether this is not only something we could do, but should we do. And for some families the right thing to do with the food allergies, avoid the food. But for some there is an opportunity to make an intervention that has a real impact on outcomes.

Jonathan: You mentioned here a child, but let's say I'm 30 years old and I've got a peanut allergy. Can I be desensitized?

Adam: Your options are much more limited. There are places that will offer you desensitization. There's new modalities of desensitization, so we're moving away from just saying, "Eat small but increasing amounts" to, "Here's a tiny little bit that you're gonna pop under your tongue. And there's, in fact, just last week we had the release of some really exciting data about sublingual immunotherapy for peanut for adults, where essentially showing that it seems to be safe to do a treatment where you put small but increasing amounts under the tongue. And the gains aren't huge, so you can get somebody to the point that they can eat a peanut, which might feel not important, but it's hugely important because if you're traveling, you wanna go overseas, you wanna eat out, it's really hard to avoid tiny amounts, and it's usually small amounts that cause most accidental reactions. But if you can get somebody to the point that they're okay with a peanut's worth of peanuts, their likelihood, if they're still telling people, "Don't give me anything with peanuts in," of having more than a peanut's worth of peanut is way lower than their chances of having a quarter of a peanut accidentally because somebody used the same knife and the peanut butter on the sandwich they made for them or didn't clean out the pan after a chicken satay.

Jonathan: What about hay fever, seasonal allergies? How should we be managing that?

Adam: For most people, have a chat with your pharmacist. So things like over-the-counter antihistamines, saline nasal sprays, and simple things like rubbing a little bit of Vaseline around your nostrils to catch the pollen before it goes in, not drying your clothes on the clothesline outside when the pollen season's at its height, closing the windows at night during the pollen season, washing your hair before you go to bed so you don't transfer pollen from your hair to the pillow to your nose. That will do the job. For the percentage of people who have more troublesome symptoms despite that, over the counter for children 12 and upwards, steroid nasal sprays, very safe, very effective. And for the 15% or so who are taking regular antihistamines, they're taking steroid nasal sprays, and despite that, it's still interfering with their quality of life, there are desensitization treatments. So tablets made out of huge doses of grass pollen or tree pollen, or there's also dust mite equivalents that you pop under your tongue every day, and over a period of time, they reduce your sensitivity. They won't eliminate or cure you, but they'll make you less symptomatic, more able to manage just with the regular medication. And the really good news in the UK is that these have received NICE approval recently, which means that a really well-respected independent organization has assessed these treatments and said not only do they work, but it makes health economic sense for our state-funded health system to be recommending them to you. But we are a mile behind in the UK on this. And for every person who receives pollen desensitization in the UK, about 700 do in Germany. Many other places in Europe in particular, this is mainstream management. But really, in the UK, there is a huge issue about access to these treatments. In the US, you can go to your allergist and get allergy shots. There's much more of a culture of giving injections there because it's easy to visit an allergist in the US in a way that it's not in the UK, where there's far fewer. But the nice thing about sublingual immunotherapy, so this desensitization under the tongue, you just do it at home. You don't need to be seeing your allergist. It's literally a tablet every day, goes under your tongue. It's for three years. It's a long course of treatment, but it gives you long-lasting benefit. It's disease modifying, and this is the holy grail in allergy. It doesn't just work while you're taking it like a nasal spray or an antihistamine will. If you do the full course of treatment, for years afterwards, your symptoms will be reduced because you've actually changed your underlying immune response.

Jonathan: For people who aren't doing that but are having, like, it's bad enough that they're taking antihistamines all the time, is there, like, a downside from taking an antihistamine every day for six months of the year?

Adam: As long as you're taking the right one, there isn't. But if you're not taking the right one, there is. So the old-fashioned ones, the sedating first generation short-acting antihistamines, which basically means Piriton, which you shouldn't be getting recommended when you go to see your pharmacist, but sadly, it still seems to happen that you are, so chlorphenamine, things like that. They firstly will impact on your alertness and reflexes and those sorts of things. They don't make you feel that much better. They're not particularly good at managing your hay fever, and long-term use has been linked to dementia in large studies. Essentially, they should just not be available. Second-generation antihistamines, so long-acting, non-sedating ones, so that's cetirizine, loratadine, fexofenadine, and those are sort of the drug names, and you can get the generics and much cheaper than buying the proprietary ones. They don't have any of those downsides. The long-term studies strongly support that they're very safe, and there's no link to things like dementia. They've got a really good safety track record, and they're more effective. So definitely start there and avoid those sedating first-generation antihistamines.

Jonathan: So I am basically popping one of those from April to October every day.

Adam: Yeah, and that's absolutely fine. You know, you have to make your own risk assessment based on do I feel better or not taking them? And given that they're a very safe medication, and that's why they're available over the counter, then it's a reasonable thing to do if you do feel better on them.

Jonathan: You've been very involved in a pretty big transformation of care for allergy treatment for certain allergies. What do you think the future of allergy treatment and prevention is going to look like?

Adam: I think the first thing says it looks really exciting. I mean, we're in a position I would never have imagined 20 years ago when I started in this field that we'd be in, which is not only are we able to diagnose very effectively, but we actually have treatment options, never mind a single treatment. We can actually discuss different ways of treating. But we're starting to see a little bit of a divergence happening. Desensitization treatment, say, for example, peanut allergy desensitization, has not proven a profitable area for pharmaceutical companies. And as a result, pharmaceutical companies are looking at different ways of managing allergy in a way that there will be reliance on medication. That's not changing your allergies or in any way redirecting your immune system. It's just essentially blocking the effect, and so you're stuck on the medicine, and it's expensive. We're not seeing the same investment in this other way of treating things, just using food, which of course means it's a lot cheaper, to change the underlying immune response in a more sustainable long-term way, which intuitively to me as a doctor feels like a better way of doing it. But the important thing is things are improving. And I often say to patients when we start on these courses of treatments, in a way, this is sort of a stopgap. So even if this does only manage your allergy for a few years, I'm sure there's gonna be other options in a few years as well, because there's so many more options now than there were five and ten years ago.

Jonathan: Well, on the one hand, I find it really depressing that you're talking about another area where pharmaceutical companies are only interested in treating the symptoms and never treating the disease because it's really profitable to keep giving you a drug that you'll take for the rest of your life. On the other hand, hearing how excited you are about all the new things that are coming is really fantastic. I'm going to wrap up with a short summary. Please correct me if I've got any of this wrong. So the thing I'm most struck by is that 10% of the people listening to this show have been told they have a penicillin allergy. So in other words, you know, if there's 100 people listening, 10 of them have been told they have a penicillin allergy. Actually, only one of them has a penicillin allergy, and that means that basically nine of these people are gonna be taking terrible antibiotics that are gonna wreck their microbiome for no reason, and they could switch to something that's much less harmful when they need antibiotics. So that's really shocking, and I think anyone who's listening in this situation should definitely, you know, go out and try and get that tested because we know how important our microbiome is if you've been listening to this show. Second thing I'm really struck by is you're sort of saying, well, actually, there was this hygiene hypothesis, and the idea was that the reason why you have all of these allergies is because we kept our houses so clean. You're saying actually, we don't really believe that anymore or, so it's only a small part of the total story. But we do know more and more that our microbes are a sort of central part of this story. And you explained that the reason why we really know this is because if you have no microbes, actually, basically, you're allergic to everything. And we know that because we can get mice with no microbes, and they're basically allergic to all food. You give them their microbes, you let them eat the food, and suddenly they're like, "Oh, no, peanut butter is delicious. I have no problems." Which is fascinating. So we understand that there's something going on in terms of our modern life because none of these sort of allergies, you know, existed a few hundred years ago. Now we see these extraordinary things. You know, one in 50 kids have peanut allergy. 20 to 30% of adults have these seasonal allergies or hay fever. So this is profoundly different. But we have made a lot of progress in understanding the underlying science of what's going on. And I was struck by you saying that, in general, we're most allergic to food that's sticky, which is quite funny. I've never heard that before. And you're like, "Well, peanut butter, hummus, it's obvious." And I'm like, "Well, why is it?" And you're like, "Well, because it sticks to your skin, and therefore what happens is that it's getting in through your skin. If for some reason you have eczema or you have some other reason that, like, your skin is porous, and particularly happens when you are a baby, and then your body sort of goes to high alert and says, 'This thing has come in, and it's not been eaten. It's therefore some sort of dangerous pathogen, and we've got to fight back.'" And you said that, again, like tying back to our broader understanding of things, we don't understand exactly why this happens for some kids and not. But you said there was some interesting data in children where their moms have a broader, more diverse diet, their kids actually have less allergies. And so again, somehow there's this link through between the food we eat and our microbiome and these allergies. And then finally, I think we ended with this incredibly exciting story about desensitization that you've been one of the driving forces behind, that this is a really huge breakthrough. And so there are all of these treatment options for things that we used to think you just had to live with, like a peanut allergy or the seasonal allergies. And it takes a long time, so I think you said it would take me three years of being treated for my hay fever, which is a long time. But at the end, genuinely, like, my immune system has been shifted. And it does remind me again a bit of the story of changing your diet with ZOE, for example, that you can sort of have a profound change to the way that your body feels and is even in something as extreme as food allergy. There's something really exciting about that.

Adam: Yeah. Sounds spot on.