GNS Vietnam 2025: Can We Prevent Allergy?

Roberto Berni Canani, MD, PhD

Narrator

Introducing Professor Roberto Berni Canani, a consultant in pediatric allergy and internationally recognized researcher in the areas of pediatric gastroenterology, food induced diseases and nutrition. He is the chair of the Pediatric Gastroenterology, Allergy and Nutrition Program of the ImmunoNutrition Lab at CEINGE Advanced Biotechnologies Research Center and the NutriTech Lab at the University of Naples “Federico II”, where he also leads the master's degree course in human nutrition.

He previously served as a member of the European Food Safety Authority panel on Nutrition, Novel Foods and Food Allergens (NDA), and is actively involved in European Union funded research projects. Professor Berni Canani has authored over 450 publications, including scientific papers and international journals, chapters of books and reviews. He is ranked among the world's top 2% most cited researchers.

Please welcome Professor Berni Canani.

Professor Roberto Berni Canani

Good morning! Good morning to everyone. You cannot imagine how happy I am to be here. Vietnam, for my first time, so many colleagues and friends, and beautiful minds from seven countries from Asia regions. Super exciting. Thank you, Mead Johnson, for this invitation.

So, the topic is, ‘Can you prevent allergy? But first of all, why is it important to prevent allergy? Everybody knows in this room that we are facing a changing scenario everywhere in the world. Regarding the pediatric age we are facing an increasing incidence, prevalence and severity of the clinical manifestation of allergic disease in the pediatric age. And now allergies is one of the top chronic pediatric conditions. We estimate that up to 30-40% of the pediatric population is affected now by at least one allergic disorder, and this is also the leading cause of healthcare costs, and not just for the healthcare system, but for the family, it has a negative impact in terms of quality of life for the patients and for the parents. And WHO, the World Health Organization, now lists allergy as one of the top three disorders that should be prevented, controlled in this century. And this is also important to underline, many patients now are presenting with not just one allergic issue, but at least 2 or 3 different allergic diseases within the umbrella of ‘allergic march’. In other words, so many patients start early in their life with atopic dermatitis, for example, and then move to food allergy, then to eosinophilic esophagitis for example. And this further increases the cost and the impact, negative impact, in terms of quality of life.

This is the scenario that we are observing. We have, for example, in Europe, up to 20 or 30% of infants presenting with atopic dermatitis. This baby presents an increased risk to develop later in life food allergy. And then allergic rhinitis, and then asthma. We are observing an increase in number at our center and many other centers at the global level of patients requiring hospitalization and care because of food allergy in the first few months of life, then the vast majority of cases, these patients present with a non-IgE-mediated mechanism. But what does it mean in clinical practice? Gut intestinal problems, diarrhea, vomiting, infant colic, and so on and so far.

Then a lot of these patients are shifting to IgE-mediated, this means more severe, increasing risk to develop anaphylaxis, for example, and hospitalization costs. We know that these patients also now present an increased risk of developing eosinophilic esophagitis, that now, in Europe as well as in United States, is the number two in terms of chronic inflammatory disorder, gastrointestinal tract level; IBD, eosinophilic esophagitis. Then rhinitis and asthma.

This is the situation that we are observing every day in our clinical practice. Patients, for example with atopic dermatitis, in this case about 40% of these patients will present also with allergic rhinitis. Or look at the patients with eosinophilic esophagitis, up to 60% will present with asthma, allergic rhinitis. This means an increased impact in terms of cost, management and negatively impacting quality of life of these patients.

So we need to move forward a new allergic prevention strategy. So, this is a problem for us. I'm a pediatrician. I'm a professor of pediatrics. And during my training, I never received some information regarding prevention. I'm a huge expert in terms of diagnosis, in terms of management, I know everything about the dosage of biologics, drugs, but nothing or quite nothing in terms of prevention.

For this reason, I tried to push my Dean to introduce an exam during the medical course, in terms of prevention, the environment, what is important for the doctor in 2025, in terms of prevention, because the cost is too high. You know, it’s unsustainable, we cannot pay for some biologics and drugs in the next future. We need to learn more and more about prevention.

And prevention is better than cure, as previously said by my good friend yesterday during the beautiful talk regarding other conditions. But if you like to design the best strategy in terms of prevention, we need to understand at least three important points. The first one, you should know something more regarding the pathogenesis of disease. Otherwise, we have no target of intervention. The second point, we know that some patients, some subjects better to say, are resistant, are resilient, against the occurrence of allergy. Why? Third important point, we need to know more about the mechanism of genetics, environmental factors, that could play a role, because we need to target these environmental factors to limit the occurrence of allergy.

Pathogenesis. Why we are able to tolerate the food antigen? Everybody in this room was at the beautiful breakfast at this beautiful hotel this morning, and we are tolerating now these beautiful foods because of the presence of a healthy gut microbiome. Because in this case, these bugs are producing compounds and metabolites such as short chain fatty acid that are modulating the gut barrier and are activating the immune system towards a tolerogenic response. Increased production of the lymphocyte Tregs. What is the role of these Tregs? It is producing anti-allergic and anti-inflammatory cytokines such as IL-10, TGF beta. And this is a sort of break for our immune system. And our immune system is able to tolerate the yogurt or papaya or beautiful fruits and foods that you received at the breakfast this morning.

But in the worst-case scenario, I can have a state of dysbiosis. I can have a problem with my gut microbiome structure and function because of the use of antibiotics, or drugs, or many other stuff that you can see later on during my lecture. In this case, I have an alteration of the gut barrier with abnormal exposure to antigenic peptides.

And this leads to an abnormal activation of the immune system. No Tregs, activation of inflammatory cytokines, IL-4, IL-13, IL-5 – signs and symptoms of allergy that we know very well in our patients.

And it is occurring not only at the gastrointestinal tract level, in the duodenum, in the ileum, in the colon, but also at the skin level and also at the esophageal level, look at the patients affected by eosinophilic esophagitis. Or at the lung level. The barrier, the epithelial barriers are fundamentally important in protecting our body against the occurrence of allergy, auto-immunity and many other conditions, including cancer. It is impossible to be a good doctor in Vietnam, in Malaysia, in Philippines, in Italy, without the right knowledge of the importance of the barrier at the different body sites.

Look at, for example, patients affected by cow milk protein allergy. A nice infant, 6 months of age like this could be sensitized to cow milk proteins, because of the presence of atopic dermatitis, or because of the presence of alteration in the gut barrier because, for example, the use of antibiotics or because, for example, the occurrence of rotavirus diarrhea, these are the destruction of the structure of the gut barrier. And after a couple of weeks, a couple of months, this baby will present the common symptoms coming from the allergy in the first two months of life, such as diarrhea, vomiting, abdominal pain. Of course, we need to also consider some genetic factors. I'm a huge fan of genetics and epigenetics in this condition. And this is just to summarize what do we know now: We’ve identified more than 100 genes that are involved in the occurrence of at least two allergic disorders in one patient. In the vast majority of cases, these genes are activated at the different level and different chromosomes, leading to different phenotypes or allergic march. For example, atopic dermatitis plus food allergy or food allergy plus asthma, different chromosomes and different genes could be involved. But this could be interesting in terms of predictive medicine. But it's also important that these genes are deeply involved in the regulation of the gut barrier and the immune system. But genetics alone is not sufficient to influence, to determine the occurrence of allergy. Less than 20% of allergy is mediated by this genetic mechanism.

Most importantly are environmental factors, the exposome. And we know now that the vast majority of these factors are influencing in a negative manner the gut microbiome, structure and function, and leads to an abnormal activation of the immune system, leading to the occurrence of allergy.

And we know now that the gut microbiome is important, environmental factors are important, because they can influence the gut microbiome structure and function, or they can interact directly with our cells. Also through epigenetic mechanism, leading to modification or gene expression, facilitating the occurrence of allergy.

But why selected subjects within the family? Also, families with an increased risk to develop allergy could be resistant, could be resilient against the occurrence of allergy? We have a lot of data in beautiful studies, performed in monozygotic twins or dizygotic twins, where there is discordance regarding the incidence and prevalence, also the clinical picture of allergy, why this?

I would like to provide you a sort of list of factors that could be protective against the occurrence of allergy. The first factor is very hard to be modified, the sex. Females are more protected, because estrogens are inducing a Th1 oriented response. Lucky, lucky, lucky.

Second point, let's pay attention to the physiological stress of the mother during pregnancy. And also the body weight of the mother during pregnancy, because psychological stress and overweight during pregnancy could facilitate the occurrence of allergy. Third point, no antibiotics during pregnancy. No proton pump inhibitors during pregnancy. Because these two drugs are able to exert a detrimental action – for each antibiotic course during pregnancy, there is an increase of 10%, increase in the occurrence of allergy.

Other important point, prenatal and passive exposure to tobacco smoke. Of course, no smoking during pregnancy and during the first period of life. Prenatal and postnatal exposure to rural environment, it is much better to live in the countryside, having some pets at home, because this stimulates the immune system toward a Th1 oriented response. Another important point healthy maternal diet. Extremely important! The gene-ecology of such [general public] are completely unaware about the importance of nutrition during pregnancy. What is important? It's critically important to explain to the mother: no ultra-processed foods, no junk foods. Let's promote diversity. Let's eat everything, because we can educate starting from the first period of life, the immune system of the baby toward a more tolerogenic state.

Another important point, let's push the importance of breast breastfeeding, in particular in the first four-six months of life. And let's continue breastfeeding at weaning, because this can educate the immune system toward a more tolerogenic state. Extremely important. This is good against allergy but also against celiac disease, as you probably know. Let's start the weaning from the first to six months of age. Let's promote diversity. Let's avoid junk foods, ultra-processed food, baby foods. In Italy, we are the champion in terms of ultra-processed foods consumption in the pediatric phase. And let's try to avoid microplastic and nano-plastic, let's use something different to feed the baby or also to provide some toys to the baby.

Last but not least, reduce contact with dust mites in the first part of life. And let's pay attention to the body weight, to the nutritional status of the patients. In terms of, let's limit the occurrence of obesity, overweight. And we need to start early in the life, we need to start at the beginning, in the first 1000 days. We need to pay attention to the diet of the mother, it is now clear that now, there are a list of prenatal negative factors that could influence the microbiome of the mother, and could influence negatively the immune system, the metabolic pathways of the baby starting in the fetal life. And there are also some positive factors, in particular factors linked to the dietary habits of the mother, that could influence, starting from the beginning of the first 1000 days, the evolution of the baby, in terms of gut microbiome, in terms of immune system structure and function, metabolic pathways, education of the immune system, education of many other body function, protection against the occurrence of non-communicable diseases, including allergy.

To demonstrate this is true, this is possible, I would like to show you the results of our trial that we performed a couple of years ago. PREMEDI. What does it mean, PREMEDI? Mediterranean Diet in Pregnancy. What does it mean Mediterranean Diet in Vietnam? To eat vegetables, fish, olive oil, fermented foods. This means this type of diet could be applied in Vietnam, in Thailand, in Naples, in United States. But we need to educate the subject, the family, toward these kind of dietary habits.

Two groups of intervention: mothers at the first trimester of pregnancy, completely unaware about what does it mean, the mediterranean diet. First group, gynecologic and obstetric counseling along with vitamins and so on and so far. And the second group receiving personalized nutritional counseling by certified dieticians to promote healthy dietary habits.

Just this. Then we continue to follow up during pregnancy and with the baby, until the age of two years. What's happened? First of all, the adherence to optimal healthy diet was very low, less than 15% of the mothers were receiving a Mediterranean diet - in Naples, the place of Mediterranean diet! But thanks to the dietary counseling we moved to up to 90% of the mothers who were able to understand the importance of human nutrition.

I remember my wife during pregnancy, she was super, ‘Oh, I need to know, I need to know everything, everything, everything. Gym, healthy diet’ and soon after the birth of my last son, bye bye. But during this period of life, the women are super interested in nutrition, in everything that could be helpful for the baby, and this is a critical period of intervention for us.

And the mothers following a Mediterranean diet were protected against overweight and obesity. The mothers following a Mediterranean diet were more protected against the occurrence of all types of disorders during pregnancy. And most importantly, the offspring of mothers receiving healthy dietary habits were protected until the age of two years against the occurrence of allergy and obesity.

We have, of course, we like to provide not only solid clinical data, but also some solid mechanistic data. So we collected the cord blood from all mothers. Cord blood means the blood of the ‘son’. And we investigated the epigenetic modulation, all the genes that could be involved in obesity and allergy. A huge amount of work. And just to summarize this huge amount of work, I could show you that in mothers receiving Mediterranean diet, we observed more than 86,000 genes that were hypomethylated. What does it mean? An increased expression of this gene. On the contrary, mothers receiving Mediterranean diet, in this cord blood we observed more than 76,000 genes that were hypermethylated, downregulation the genes.

What are these genes? In the vast majority of cases, these genes were involved in metabolic pathways leading to overweight, obesity, or allergy. One of the most important differences were for Leptin. Leptin plays a crucial role in obesity, as you probably know. Look at this data: methylation rate of leptin is super high in the mother, in the cord blood of the babies receiving Mediterranean diet. What does it mean? Low expression of leptin, low level of leptin, it is protective against the occurrence of obesity/overweight. But the leptin is also extremely important against allergy because the leptin is one of the most important inhibitors of Tregs, and Tregs are the most important cells that are able to protect our body against allergy. More leptin, more obesity, more allergy.

In my center, 60% of patients affected by eosinophilic esophagitis or asthma are affected by obesity. Do you know what they are doing, the allergists in my center? Nothing. They provide just steroids, drugs, biologics. Please, let's check the body weight of these patients. Let's calculate the BMI, a few seconds, and let's prescribe something to reduce the body weight. Because you are trying to treat asthma, but you should understand that these patients affected by asthma, obesity, are unable to respond to this kind of treatment because of the presence of leptin.

How can we move my car with the break? Impossible. I can buy a beautiful Ferrari, but if the break is on, not a chance to go to Naples or to Manila or to other beautiful countries in Asia. So, this is the situation. More obesity, more severity, no response to drugs.

So, we need to pay care to the nutritional status of these patients. And I repeat, pediatric gastroenterologists, pediatric allergists are not paying so much attention to these kind of problems. And this is the key. And we need to pay attention also to the diet of the mother during pregnancy, as suggested by different studies, including our studies, because the mother receiving these type of foods, this can educate the microbiome of the mother, and this is able to provide the compounds and metabolites able to educate the immune system of the baby starting from this period of life. But soon after birth during lactation, we know now that if the mother is receiving an unhealthy diet full of this type of foods, these are able to influence the microbiome of the mother, the microbiome of the baby, but most importantly, the concentration of bioactive compounds in the breast milk. We are performing an ambitious study sponsored by Italian Ministry of Health. We are collecting breast milk samples from 1000 mothers, and we know everything about these mothers. How many hours in gym, which kind of Netflix program is watched? Because we’ve developed a beautiful app, where the mother is recording everything, including the diet. If the mother is receiving this type of diet, we can observe a decrease in DHA content in the breast milk. Yes, we talk about the DHA content in breast milk or HMOs, or immunoglobulin or lactoferrin or butyrate.

What could be the role of a breast milk sample from a mother receiving junk foods every day? We can decrease this chance to help this problem. But maybe this is one of the explanations why, if you look at the literature, the Cochrane review regarding the importance of breast milk against allergy, the conclusion is we cannot have a solid data to support the concept that the breast milk could be effective against the occurrence of allergy, simply because you should analyze the diet of the mother. The breast milk is not like a beautiful, I don't know, Sprite or Fanta, where the taste is exactly the same everywhere. The breast milk is influenced by many environmental factors. First of all, the dietary habits of the mother. So please pay attention to the dietary habits of the mother or your mother. Explain in simple words that it is much better to receive this kind of diet instead of this kind of diet, because at the end of the day, you can induce a long lasting protective action against infectious diseases and many non-communicable diseases, including allergy and obesity.

In other words, our babies are losing an immune-supportive diet, our babies are not receiving now fish, olive oil, fermented foods, vegetables. They are more prone to receive these type of foods: sweeteners, emulsifiers, ultra processed food. Because they love this type of foods.

This is one good friend of mine, Carlos. Carlos Monteiro was the inventor of the classification of the quality of the foods. The ultra-processed foods are number four, or group one, minimally processed foods. Yesterday we had a beautiful dinner with minimally processed foods. Thank you Mead Johnson for this. But if you look, if you go more outside the hotel, outside the Mead Johnson dinner, we can find so many shops and restaurants providing these type of foods.

And what Carlos is saying is pay attention not to the quantity, but the processing, the degree of processing of the food. Because this is the key.

This is the scenario in Italy, a mother with a son. Not buying vegetables, fruits, but this kind of stuff. Because the baby love it, it is much easier to prepare and to provide this type of food. And now we know that the increased prevalence and severity of allergic diseases are paralleled with the increased exposure to ultra-processed foods. There are places in the world such as United States, UK, where more than 60% of the caloric intake is deriving from ultra-processed foods.

There are people in my country, four, six months of age that are unable to recognize a pear or kiwi. They have never seen a pear or kiwi. They are able to recognize all the brand names of junk food, all, but never are aware of a pear or kiwi. This is the situation in Italy, my country. I really hope that in your part of the globe you, will be much, much better in managing the dietary habit of the next generation of babies, because this is extremely important, because we know now everything about the detrimental action of this ultra-processed food on our body.

We know the effect of advance glycation endproducts that are produced when exposing the foods to high temperature, or the effects of emulsifiers or packaging materials, because this type of components of ultra-processed foods are able to modify the gut the barrier, the gut microbiome, the gut permeability and the immune metabolic pathways, leading to an increased risk of developing non-communicable diseases. From the brain, Parkinson disease, to the lung, asthma, cancer, IBD, celiac disease, allergic disorders. All these disorders are increasing. Why? Because the first step is this.

And these type of foods are able to play a detrimental role in regulating the structure and function of the gut microbiome, reducing the mucus thickness, increasing the amount of detrimental bugs, increasing the exposure to detrimental lipopolysaccharide. Lipopolysaccharides are some component of the membrane wall of the bacteria, that are able to play an important role in communicating with our cells, and these facilitate the occurrence of metabolic disorders and immune-mediated disorders, including autoimmunity and allergy.

To convince you that this is true, I would like to show you some new experiments that we are doing at my lab. We have this beautiful toy. This is an artificial human gut microbiome system, and we can collect stool samples from our healthy babies living in Naples. We collect the stools. We can incubate the stools using this machine, simulating our gut with ultra-processed foods. And we can follow day by day, week by week. what's happened in the gut microbiome structure and function of this baby. And these are our results: exposing the gut microbiome of a healthy baby to more than three portions per week of ultra-processed foods leads to the alteration in gut microbiome.

In other words, the gut microbiome is losing more than 1400 species of bacteria, that are extremely important because they are healthy bugs, these bugs play an important role in protecting our body against the occurrence of allergy, because these bacteria are able to produce short chain fatty acid indole and glyoxalase. So, what does it mean glyoxalase? Glyoxalases are a particular enzyme that is produced in the healthy gut microbiome that is able to protect our body against the aggression of ultra-processed foods, it is fascinating.

And you know which is the most important bacteria producing glyoxalase? Lactobacillus, for example, is a huge producer of glyoxalase. So, we need this kind of bacteria because this kind of bacteria could protect our body against the aggression of, for example, one meal of junk foods per week, it is nothing. But if you are receiving every day, we are destroying this protective mechanism and this could facilitate the occurrence of allergy.

And we are purifying this bacteria from these experiments, and we are identifying the particular lipopolysaccharide, the lipid A that is responsible for communicating to our cells. And we can incubate blood cells from healthy control swith this compound from this microbiome that is exposed to ultra-processed food. And what we found is a severe dysregulation in immune system.

So now we know everything: how much junk foods, the bacteria that we are losing, the bacteria that are present, the bacteria that are able to produce these compounds and that because these compounds interact with our cells inducing alteration of the immune system, inducing allergy, everything is clear. But these ultra-processed foods are able to also interact directly with our cells. This is another study by our group. We analyzed the dietary habits of children affected by food allergy vs healthy controls, and we found dramatic difference in terms of dietary habits. In other words, the babies that are protected against occurrence of allergy were consuming less processed foods. The consumption of ultra-processed food in children presenting a food allergy is much higher.

Then we have this beautiful machine, it is an AGEs reader, in other words, we can measure the accumulation of ultra-processed foods in the body of the child. And we found exactly the same difference. And then we move to the lab, incubating our internal sites or immune cells with ultra-processed foods, and we found that what we now commonly found in subjects affected by food allergy, alteration of intestinal permeability, alteration of the immune system, increased production of allergic cytokines, all the factors that are leading to the occurrence of food allergy.

Going back to our clinical practice – breastfeeding. We are observing, you cannot imagine, how many patients on breastfed with this kind of diaper: blood in the stools, allergic proctocolitis. How is this possible? I'm a mother. I'm young. I'm receiving the best of the best, breast milk, and my son is presenting blood in the stool, allergic proctocolitis. Half percent of patients affected by allergy in Italy are on breastfed.

Why is this possible, how is this possible? We are investigating the quality of the breast milk of this mother. And what we found is this: the concentration of ultra-processed foods, the concentration of advanced glycation is double.

You should pay attention to the quality of the diet of the mother. Why are these infants are presenting proctocolitis, inflammation in the last part of or the gut? Come on, it’s easy! Do you know, if you have a baby that’s receiving breastmilk, eating and losing stools, 1-1-1-1. Because the intestinal motility is super fast, and the gut is less than one meter. The accumulation, the stool, is just in the few centimeters. In these few centimeters there is a super high level of ultra-processed foods, delivering and inducing inflammation. This is the cause of allergic proctocolitis.

So, we need to pay attention to this stupid evidence, but this is extremely important, because maybe we can manage allergic proctocolitis, not only providing a special format, but also educating the mother toward the more healthy dietary habits.

And all these concepts have been presented in this document that was prepared by the European Association for Allergy and Clinical Immunology, stating that ultra-processed foods are an extremely important factor in driving the occurrence, in driving the disease course, of allergic disorder, in particular allergy in the pediatric age.

And we know everything. We know the type of foods. We know that these foods are full of this compound, advanced glycation endproducts. These products are recognized by receptors located everywhere in our body, called RAGE receptors. This leads to inflammation toward Th1 immune response, alteration of intestine permeability, and microbiome. Easy. We know everything about this problem. We need to fight against the consumption of ultra-processed foods.

And this is extremely important. The last generation of Samsung smartwatch are presenting AGEs readers. You can monitor the quality of your diet with your smartwatch.

And I am very happy for this. Unfortunately, I am not the owner of this kind of watch, but this is extremely important. But this is another evidence that it is important, not only against allergy, but also against many other conditions, because we need to move over to this type of lifestyle. We need to promote early in life healthy dietary habits to limit the exposure to detrimental compounds, including microplastics and drugs. We need to pay attention to the skin, if the baby is affected by atopic dermatitis. Because all together, this factor could induce effective prevention against the occurrence of allergy.

For this reason, I'm not a super fan of providing just, very, very stupid, but let’s say not high-quality evidence, regarding the importance of introducing solid food - this is true, this is important. It's important to educate the immune system early in their life, pushing diversity, provide the antigenic food. But maybe this is not enough. We should pay attention to the maternal diet during lactation, to the quality of the diet during the weaning, try to avoid ultra-processed foods and drugs in the babies because in this case, we can educate the immune system in a specific way. Provide the antigens such as peanuts and egg, and at the same time can educate the microbiome, I can modulate the gut barrier structure and function, I can induce a more efficient immune tolerance regulation.

It's possible to do this kind of stuff? In Finland, yes, in Finland it's easy, because in Finland there is living around 2.5 million people, nothing compared to 100 million people living in this country. But if you can educate doctors, dieticians, nutritionists, families, for ten years using this kind of cartoon – let’s spend time outside, let's go outside with the pets, let's eat this kind of stuff, let's avoid junk foods and so on and so far. They observe a dramatic reduction in hospitalization because of allergic asthma, dramatic reduction in drugs used because of asthma, ocular rhinitis and food allergy. So, it's possible, it's easy, and cheap. But we need to move together, because again, according to our estimation, in the next 15 years more than half the European population will be affected by at least one allergic disorder.

Now we know that the prevalence is increasing because of the exposure to detrimental environmental factors, we know which are these detrimental factors, and this is one detrimental factor that we can monitor every day in our clinical practice, in particular the diet. And we are also knowing a lot of beautiful data regarding the immune tolerance mechanism, the importance of the gut microbiome, and these are able to simulate new strategies in terms of allergy prevention.

For all these reasons, I feel that the outlook of pediatric allergy is bright. So, what will be your answer to the question: Can we prevent allergies? Come on? The answer is yes, we can! And we must do it.

Thank you so much for your attention.