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

0:00Welcome to Zoe Science and Nutrition, where world-leading scientists explain how their research can improve your health.

0:14In a cafe downtown, a customer notices something changing. It's just a tingle on the lips. It feels harmless. But within minutes, the situation has become life-threatening. Meanwhile, in a restaurant a few doors down, a diner feels queasy and bloated. Their eyes dart around, looking for the quickest way to the toilet. Food intolerances and allergies were once rare. But within a single generation, they've exploded. Until 20 years ago, most of us had never heard the word gluten.

0:47Today, gluten-free products have their own shelf at the grocery store. Dairy food options are also widely available. In the past, these allergies were vanishingly rare. But now, conditions like peanut allergy and seasonal allergies like hay fever have surged, reshaping what we can eat on a plane or put on our kids' sandwiches. Today, restaurants ask for allergies and nut-free zones are increasingly common. What has driven this change? Cleaner homes? Changing diets? Or something else entirely?

1:18In this episode, Adam Fox, professor at King's College London, one of the world's leading allergy researchers, helps us to unravel the science behind them. What's really happening inside our bodies? Why are some people more affected than others? And crucially, what can we do about it?

1:39Adam, thank you so much for joining me today. Pleasure to be here. So, we'd like to kick off our show here at Zoe with a rapid-fire Q&A with questions from our listeners. Are you up for that? Definitely. And we have some very strict rules. Okay. You can say yes or no, or if you have to, you can have a one-sentence answer. Let's do it. Adam, are people born with food allergies? No. Can you develop a food allergy as an adult, even if you've eaten that food your entire life?

2:09Yes. Were our hunter-gatherer ancestors allergic to pollen? No. Do most people who think they have a penicillin allergy really have one? No. Are allergies and food intolerances the same thing? Definitely no. And finally, what's the most common misconception about allergies? I think it's that allergies are trivial, because for some people, they are actually life-defining. Now, my sense is that allergies are getting increasingly common.

2:43When I was young, I'd never even heard of 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 the US and the UK? 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 1,500 kids, and there was one child who had a peanut allergy.

3:22And everyone knew about it, because it was such a strange thing that this child would have a terrible reaction if you 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 peanut. Now, my son went to the same school that I did. We still live in the same area. And he was 30 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's a lot of them.

3:57And I knew for my son's friends, when they were coming over to play, that a number of them would present us with their EpiPens when they arrived. And, you know, you 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 30 years. And that's reflected in the data. If you gather a lot of studies together, we can sensibly estimate that around 5% of children in the UK, US, for example, will have a food allergy.

4:31Now, 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 20-year period, there was a troubling in the number of people presenting to emergency departments with severe allergic reactions. So, this is a very significant increase. Year on year, 6% or 7% to get to those sorts of amounts. And if you dig in to, well, why is that happening?

5:03Is 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 dropped off because of COVID, that really impacted the ability to collect reliable data, there was a doubling of food allergy during that period reported.

5:34So, 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. The thing that springs into my mind is peanuts 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 I'm a bit mean on the peanut?

6:06No, 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 1 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, kiwi, sesame, a relatively small number of foods in the bigger scheme of things account for the overwhelming majority of food allergy that we see. But peanut is often being used as the model in the search studies because it's serious, you don't grow out of it, unlike milk and egg allergy, which commonly you do.

6:43So, it's been a real focus of academic attention. But then also, it is 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. Did you just say that the most common cause of, like, serious allergy is milk? The most common cause of fatal anaphylaxis, the most common cause of anaphylaxis in younger children is milk. It's not peanut.

7:14Now, 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 going to 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. I want to come back to that, but we were just talking about peanuts, and I'm sort of curious.

7:48You said there has been this big rise. It is a really important part of the allergy. Is this true everywhere around the globe? 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.

8:22And amongst British-Asian families, if they've got a nut allergy, it's more commonly going to be something like cashew, pistachio, walnut 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. I might have thought I'd be allergic to the things I've never been exposed to.

8:54But you're saying, actually, I'm allergic to the things that I grow up with. As we have developed a better understanding of how you become allergic in the first place, it sort of makes sense that it's going to be the things that you grow up with. Not just anything, it's going to 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.

9:26But another good example would be sesame. So, often both of them are eating 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.

9:59So, 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 you're at risk of developing allergy. You're saying we tend to develop this when you're a very small child, and that what's happening is actually my immune system is getting exposed to 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.

10:45And 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. 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 it can be ignored.

11:24And 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 recognise what those things are so it can kill it even more effectively next time round.

12:00But 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's 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's sat on your skin barrier is food, because that infant has never eaten it before. Why is the skin not keeping these things out?

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13:38It's a strategy, and it starts with the next thing you put on your plate. Most people wait until they notice a decline to start caring about their brain. But longevity isn't luck. It's a choice you make before you need it. Don't leave your cognitive future to chance. Go to zoe.com slash brainhealth right now to claim your guide. That's zoe.com slash brainhealth, or click the link in the show notes. 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,

14:08you 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 that 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. And Adam, what is eczema? So eczema is an itchy, dry skin condition that for many people is mild and just gets better as they get older.

14:46For some, it can be much more severe and persistent. And it's characterised 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's sat just underneath the top layer of your skin

15:19and cause inflammation. So you get an inflammatory component as well. And that combination, that leakiness and that inflammation, creates an environment where things can go a little bit skew-whiff from an immunological perspective. I remember when I started this specialty, there was so much debate about, was this 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.

15:53And 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. And if I don't have eczema, does that mean I'm never going to develop an allergy? You're much less likely to, but we do see people, not commonly,

16:26who don't really report any eczema in early childhood, who still go on to get food allergies, and certainly other allergies as well later. We've 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 savannah. Yeah, you can sort of dig into antiquity and find occasional cases of things that sound like they were probably allergy.

16:57I 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 want to get a clear sense of change over time, there was a paediatrician in Manchester called Bostock in the early 19th century. He had seasonal allergies. He recognised 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.

17:29And 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 and 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 no more than the 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.

18:05And so when did it start to increase and go from vanishingly rare to you're now saying 20% to 30% of all adults? 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 centres and different time points to suggest that there was a big increase 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.

18:38I think a lot of people have quite mild allergic responses to the pollen, a little bit of an irritation. Is this like a sort of impactful issue for some people? 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'll be fine, and they would be.

19:08But 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,

19:42which 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. I guess it would be the same for being at work in the summer versus the winter.

20:12So 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, 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.

20:43And 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. I'm thinking that the Americans calling the 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 it almost takes away how serious it might be for people who've got sort of more extreme responses to it. I think absolutely, yeah. So it's easy to consider it something trivial, but for a material minority, it's far from trivial.

21:16I'd love to come back to the other allergy that we talked about in the quickfire 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. Yeah, it's monumentally over-diagnosed. And the reason is, 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

21:47somewhere on their medical notes. They've been told, don't have penicillin, you're allergic to it. And we've replicated that. We, 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 labelled as being penicillin allergic. And would this be similar across the Western world? Yeah, absolutely. And very similar studies from Europe, from the US, from Australia, very, very similar. And then when you ask people,

22:18where 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

22:49that 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 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 and you're getting the right antibiotics because people can't give you the normal first lines

23:22because 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. So how many people do you think actually are allergic to penicillin? Well, I can go further and think because the studies where you get a group of people who have been diagnosed and actually do the correct testing

23:52and 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 labelled 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. Now, if you were allergic to penicillin, say you're doing it with an adult,

24:22someone said, what would you expect to see happen? 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, there, you'll probably be fine and you're not allergic, so just do it because you'll get it wrong one out of 10 times.

24:53So they need a history taken from somebody that knows the right sort of questions to ask. And often it's, you can't get much sense back because they'll say, this was 40 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

25:24of 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 going to 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. So that kid needs a very brief sit in your waiting room, have some penicillin, de-label.

25:55So 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? 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.

26:26Now, 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 going to 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. So, we've 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,

26:57it was like one kid who had a peanut allergy and now it's like a quarter of the school or the fact that 200 years ago, you couldn't find somebody who had these seasonal hay fever allergies. What's changed? So, the prevailing theory for many years was the hygiene hypothesis, what 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

27:28that 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, given modern living and the difference between how we live now from 100 or 200 years earlier and the lack of threat from different microbes that there is these days, that first child had relatively little pressure

27:59on 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've 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

28:31was 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 looking, 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.

29:01And 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

29:32showing 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 what we've really nailed 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,

30:05or whether having a certain type of gut bacteria leads to you getting allergies. That's really hard to disentangle, and it's going to take a long time to do that. But then, of course, as you'll know, anyone in this space knows is this is such an almost overwhelmingly complex area, because we're not just talking about a, we often refer to 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 colonising your gut, then yes, that does seem to be associated

30:35with 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,

31:06but culturally very similar places. 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 that sort of issue 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.

31:39There'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? Before we move on, why are you so confident

32:10that the microbiome plays an important role? 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. I'll try and give a very, very quick example. If you go to mouse models,

32:41so 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. They're basically sort of allergic or intolerant to everything? Yeah, so they're over-hyper-reactive in terms of their responses to things. Whereas regular mice that do have a gut bacteria, if you feed them allergenic foods very early,

33:12they'll develop tolerance to them. Whereas if you rub those foods into their skin, into a braided skin, you can make them allergic to it. Going back to what we talked about earlier with the food allergies. 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. 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

33:42that 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, you know, 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

34:14who had milk allergy. And if their mother wasn't able to breastfeed, they'd be put onto these hypoallergenic formulas. And they were randomised 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,

34:44be less likely to get other allergies. It just didn't make any difference. So understanding it, but then knowing how we can influence it in a way that's going to improve outcomes to very, very different questions. 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, a hundred years ago because you said

35:16there has been this explosion and all of these allergies. Yeah. And another little interesting bit of evidence, recent studies looking at dietary diversity in mums and 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 mums 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. I'm conscious that

35:46we 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? Sure. They are very different things and the terminology is really important. But the bottom line is that an allergy does involve your immune system and 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,

36:17which 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, so 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

36:48that 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 diarrhoea 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 a month things go back to normal and that's very common

37:18in 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

37:48whereas 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 an 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

38:19and 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 recognise that food so that 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

38:50because fatal anaphylaxis thankfully is very very rare even amongst allergic populations you've used that word anaphylaxis a few times I have no idea what it means 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

39:20you might feel lightheaded dizzy you might collapse any of those symptoms that means this is 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 I'm reminded of the question I asked at the very beginning

39:51where I said do all allergies happen in childhood and you said no and I would say at a personal level I do have like these seasonal allergies this hay fever fairly seriously now and I don't remember having it at all until I was an adult 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

40:22and 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

40:52and 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