This presentation is by Dr. Maria Carmen Collado, Medical Scientist at the Institute of Agrochemistry and Food Technology (IATA-CSIC).Narrator:

Introducing Doctor Collado, a distinguished researcher with expertise in microbiology, food science and nutrition. Doctor Collado holds key positions in esteemed organizations, including the Executive Committee of the International Society for Research and Human Milk and Lactation and the Spanish Society of Microbiota, Probiotics and Prebiotics. She is currently a scientific researcher at the CSIC in the group of lactic acid bacteria and probiotics at the Institute of Agro Chemistry and Food Technology in Valencia, Spain.

Recognized for her contributions, Doctor Collado has received esteemed research awards, including the ESPGHAN Young Researcher Award and the Scientific Young Research and Nutrition 2021 from Fundación Jesus Serra Please welcome Doctor Collado.

Doctor Maria Carmen Collado:

Well, again me, I'm so sorry, but I'm going to talk now a different story with some relation with the breast milk and breastfeeding. But we are going to talk about the microbiome and its impact in allergy conflict of interest. Well, we already know from all the talks of this morning that early life is a critical window of opportunity where we can try to modulate the microbiota in those cases where the microbiota is altered. When this happen, I mean, we already talk about the month of birth, the use of antibiotics, maternal health status of prematurity, etcetera. And also we know that microbiota development, early life are related to, health outcomes. And these balances or alterations in, in this process are linked to a higher risk of disease later in life, mainly non-communicable diseases, including obesity, allergy, immune diseases, etc..

But you can ask me, Maria Carmen, you are not right. Some of these diseases have genetic background and I can answer yes, but the increase that we are facing now in our society cannot be explained. Yes, with a genetic background. Then something else is promoting and increasing the numbers of infants that have different diseases. Then we are going to focus in narrative because they Whole area is the allergy that we are going to talk on. Again, maternal diet. Both have an important role in the risk of allergic disease in our infants. Here you can see two papers where they associate the maternal diet intake or the maternal dietary patterns. And the risk of disease the first one is a study led by Karina Venter in US, where she analyzed the maternal diet in around 1000 individuals.

And they found that higher intake of vegetables and fruits and these things were associated with a lower risk of allergic diseases. You can see how these other diseases include rhinitis, atopic dermatitis, asthma, eczema, etc. the other one is a study run as well, with a combination of, different themes in France, in Australia and other things. And they also collect the information of the maternal diet during pregnancy.

And again, they found that resistant starch consumption was associated with a different phenotypes in one was associated with a prevention of the infant with and also the other one with no differences with eczema. Well, you know, that diet is one of the most important tools modulating gut microbiota. And we had the good luck to collaborate with Carina Venter and we check we use the same index, this healthy health index that she developed in our cohort in Spain. Of course, with some changes, because you know that the diet in US is totally different than the diet in in Spain and mainly in the Mediterranean area. Where is my place.  We found that these different clusters or different indexes when associated with different dietary patterns, and we found as well that vegetables and fruits were associated with a better microbiota. In this area as well, there are two different papers are even more that associated, for example, that the maternal studies of a specific bacteria that is prevotella during the pregnancy is associated with a protection of food allergy problems. Other work also suggests that a specific microbial signatures in in IGA mediated food allergies in one. Also, they found that higher Prevotella was found in control individuals with not problems of allergy, and also showed higher short chain fatty acids. What you already know from my first presentation that some bacteria are able to produce short chain fatty acids like acetate butyrate, and other, they promote a gut homeostasis status, an adequate gut system. Then specific bacteria that can be modulated by diet reduce the risk of allergic diseases in our population. How this happened I know that this picture is quite complex, but just take a look to the differences in terms of healthy. Cascade of anti inflammatory pathways compared with a food allergy where there is an altered microbiota. Well, there is a pro-inflammatory, pro-inflammatory signaling that promote a response, increase the symptomatology and the problems. And then the other side, as I love always to mix the observational data in humans with preclinical studies because we have to know which are the mechanisms in this study they analyzed whole dietary fiber, we are talking about this dietary fiber during the whole morning are influencing the maternal gut microbiota and lastly they activity the short chain fatty acids. And how this has so influence a specific short chain fatty acid receptors in embryonic preventing the risk of metabolic syndrome in the pups and later in life, then again how food or specific nutrients and modulate the microbiota, the activity of the microbiota and then the risk of disease. What do we know about the infant diet microbiota analogy. Well, we already discussed this morning that breastfeeding practices reduce the risk of epidemiological data just and shows that breastfeeding practices reduce the risk of allergic problems. We know as well that when and how the complementary food is introduced may influence as well the risk of disease. There are many, many studies in literature.

Of course, this is like a short term flush with the specific studies that demonstrate that infants who develop allergy had a distinct microbiota profile during early life. In other study, also, they check how the microbiota change during the first 100 days and beyond 100 days, and how the different specific bacteria are not just bacteria. Also the diversity, I mean, the number of species that we harbor in our gut when we are talking about species, number of species is like when we are going to prepare a cake in one day well we have just one spoon, but in the other table we have this spoon, the, the cooking machine, the knife always is easy to prepare. The cake using all the tools that we have in the table with more tools, then this is the same. If we have more tools, more bacteria, we can do more fine tools in a best way. Then this is important to mention. And when we are talking about the diversity. So we have to distinguish early life period and adult life in early life. If the kids have lower diversity, I mean less number of bacteria. Why? Because the gut microbiota is compounds mainly by bifidobacteria is the more predominant then the diversity is low. But when complementary food is introduced, the microbial diversity starts increasing in quantity, but also bacterial total load. The quantity is also important. Then new species are going to appear.

Then the diversity is going up. And then and that time is when we have other bacteria that can produce other things that also are benefit for our kids. Then in this study, they check the different times in early life in the babies, and they found how babies with younger babies had less, or how to say less bacteria like are similar to that to the infants, while the babies that have atopic dermatitis later in life has also less richness, less lactobacterium less Prevotella. Again, Prevotella less bifidum are associated with a higher risk of disease. Okay. And in general, we can say that in early life, the first year of life, babies are risk of allergies. When they are born by C-section, they are exposed to antibiotics. They lack breastfeeding diet again. But that's how environments are playing an important role because are also modulating the changes in diversity and in composition. But not just bacteria are modulating modulated by these factors as well. Other organisms that we were talking about today, yeast and fungi are playing an important role as well. In allergy. You can see different publications in a good in a good papers. I would like to highlight this. The last one led by Marie-Claire Arrieta, a colleague in Canada. And they found how atopic width was influencing the microbiota, but also the microbiota, the percentage of fungi and bacteria. And they found less Saccharomyces, the you know, this like bacteria that is used in bread. They say beneficial bacteria was present, was lower present was lower in infants who develop later atopic related problems. And also in this study is compiling all the data from the child cohort, also in Canada are they found as well. The allergy risk was influenced by the presence of different fungi on the gut and 80% more adequacy in predicting allergies using the fungal data. Then fungal data also is going to provide us new perspective to understand the relation between diet, microbiome and health. But what about the microbial activity? Because we were talking about the metabolites from them, metabolites that the microbiota can produce, and here as well you can see a different slice of different studies showing how a specific metabolite during early life mainly butyrate. And also you can see propionate may reduce the risk of allergy problems in this other study. In the second study also they found that metabolic profile or metabolite profile was also associated with a food allergy.

And it's not just ATP, it's also food allergy and also asthma. And all of them mentioned that butyrate would be a protective metabolite produced by bacteria that can reduce the risk. Then the next question would be which bacteria is producing butyrate?

We know that Bifidobacterium that is present early in life produce mainly acetate. Then at the beginning the first month, there is not butyrate. But we know that once the complementary food is being produced, there are older bacteria that appears. And among these bacteria there are bacteria, butyrate producers in the gut. Then most of these studies were done in kids a little bit older than early life. That's the reason that these butyrate is playing an important role and would be considered as a potential biomarker. How these butyrate affects the intestine and which are the mechanisms in I like this slide because includes all the potential factors may influence the gut microbiota on the neonates and how these butyrate bacteria interact with the epithelial cells. How the butyric acid influence the naive T cells and produce and reduce the foxP3  gene regulation, reduce the anti-inflammatory cytokine production interleukin ten and increase the effector T-cells, promoting an excessive immune response. Then we have to modulate in the top. We have to modulate the microbiota to signal in another way the rest of the cascade and to increase the pro-inflammatory signal, induce the production of interleukin ten, and also increase the expression of FoxP3 and regulatory T cells. Because with this, maybe we would be able to reduce the risk of disease, or at least to reduce the excessive, immune response that we observe in allergy related problems.

Again, we are going to talk about milk. We know that human milk have also different factors immunoglobulin A, cytokines, oligosaccharides that also all of them are associated with a low risk of food allergy in the infants. In our team, we were also analyzing the Bifidobacterium presence in the milk from women who had allergy related problems compared to healthy ones, and we observed less Bifidobacterium in in those moments when those mothers who have allergy related problems. In addition, in other collaboratives study with Maria Hellmann in in Sweden, we found and it was mentioned in the pediatric Allergy and Immunology paper, that allergy development because we analyzed kids, but we analyzed kids who developed allergy at seven years of life, and we analyzed the breast milk samples that those kids receive. And we found that allergy development was associated with a consumption of the breast milk with a reduced microbial resistance during the first month of life and also we found a distinct profile of the milk microbiota in moms who had kids that develop allergy compared with kids, that remains healthy. As you can see in the in the patterns, different colors represent different bacterial groups, and you can see the difference in the colors, mainly this orange one that is, related to the streptococcus presence.

And the question, the next question is, okay, we know that diet, influences microbiota, maternal diet has influenced the risk of disease. We know that microbiotas influence the risk of allergy. Then can we modulate the maternal neonatal microbiota and then reduce the risk of disease. What do you think?

We know that there is really an intimate relationship between the diet, microbiome and immune system that has been associated or has been linked with the risk of disease. But the question is when we have to design these new strategies to modulate the microbiota during the pregnancy, during the lactation, and who would be our target population? The moms, the infants, both, or maybe even we have to think before pregnancy how to take care of our microbiota before conception for males and for females, for both to promote another great environment and still we do not have enough evidence to report this, but I would like just, to show some examples that we have in the literature. The first one is how probiotics may influence a specific compound in human milk. Tomorrow, after we get to that, we know that there's an anti-inflammatory cytokine that promotes oral tolerance and also promotes the IgA production. When mom consume the probiotics, there is an increase of this component. And we know that is going to have an effect on the neonate. Second example probiotics during the lactation may influence the quantity and diversity of human milk oligosaccharides. and third whole, probiotic during the gestation and lactation may influence the butyrate producer microbes. Then here we have some tools, but still there is a lack of information about which type of probiotics with those in which moment, which matrix. Then from here, I would like again to promote the research under the area. And when we are talking about infants mainly infant restoration, you know that now there are like different possibilities. You know, the vaginal seeding and now there is a fecal microbiota transplant from moms to the babies that were born by C-section in order to be exposed to the maternal microbiota, because we know that is really important for the colonization. I mean, from our own microbiota, then all these things are there, diet is there, but also maybe other type of interventions like mindfulness yoga, veggies, therapy with veggies. Then as still this field is evolving. But two nice questions that were published in microbiome paper. Should we modulate the neonatal microbiota and if yes, what should be the goal. And the second the second paper was that we need more data because we are at the beginning of this. And for this also, we need to define which microorganisms, which functions, which metabolites, which would be the effect short or long term, because maybe we can develop some intervention, but it's just at the beginning. I mean, we can see differences at short term but nothing long term. Then what is the rationale then we have to think about all these things, trying to modulate and to promote the microbiota through diet and the effect on risk of disease and in this case or for this audience, allergy, take home messages. Nutrition impacts the cycle of life overall starting before the baby's born and continuing with the infant feeding maternal diet influences the microbiota and also some breast milk components, which effects on infant health. Maternal microbiota is recognized as the main determinant of the child health, providing a specific signals to guide the immune system development, maturation, and also neural cognitive things. And we know that alterations in infant microbiota has been associated with allergy risk. And there is the open door for new possibilities and new design of interventions trying to modulate these microbiota through the diet.

And thank you very much to all of you.