 Thank you very much, Fabio Pilaran-Cosiangel. Thank you very much for participating in this table, discussion table. And also, I think it's this very interesting discussion entitled One Side Doesn't Fit All, How Personalized Nutrition and Microbiome Caught in Nutrition Interventions. So just to break the ice, Fabio, we're going to start with a round of questions to put the context of stands for health. In your presentation, Fabio, you just gave a very nice overview about the importance of nutrition in obesity and other weights. What are the current trends now? And what is the role of personalized nutrition to do with this terrible obesity and other weights? Yes, thank you for the question. In the last three years, our attention was focused on COVID-19 pandemic. But we know that also in this year, obesity was the first cause of disability and death also in Europe. And the increase of obesity is higher in richer countries of Europe, of North America, and Oceania, in particular. Two tiers of older, one in three children, are in this condition of overweight and obesity. We know that socioeconomic status plays an important role in this condition. In fact, family with a low socioeconomic level are at high risk of developing overweight and obesity. And low and medium income countries are now facing with the double burden of malnutrition. And so they have specifically also in the same family, we can have subject in under nutrition and subject in a condition of overweight at high risk of developing non-communicable disease. In the last three decades, nutrition or guidelines try to give advice to solve this problem, saying this thing from healthy food versus non-healthy food. But these kind of strategies often fail it. In fact, the rise of obesity is still ongoing. But on the contrary, personalizing nutrition may be the good choice. In fact, recent evidence showed that particularly taking account our individual genomics and, of course, gut microbiota give important results in preventing and treating overweight obesity but also diabetes. In some cases, this kind of strategy is also important to improve other approach, other therapeutic approach. Thank you very much. This is very helpful. Pilar, we observe in different intubation a high variability, a drastic variability between individuals. As an expert of microbiome and microbiota, what do you think is the impact of microbiota in this extreme variability we observe? I think it's likely to be a big factor. Obviously, not the only one. Genetics are also going to matter, of course, and the interaction between genetics and microbiome as Anonymous was saying is definitely something that needs to be much further studied. But composition of the microbiome, I think, is certainly going to be one of the aspects that influence whether an individual responds well or not to a given intervention. And it's probably something that we need to study much more closely in the future. I mean, it's clear that, for instance, if a bacteria is not present at the start of a given intervention, it cannot increase, right? Even if we give all the best foods to promote the increase of a bacteria, we need to count on the fact that the bacteria is already there. Otherwise, that strategy is not going to work. On the other hand, that's not the only thing, because, for instance, in our data, I didn't have time to mention it, but we've actually looked a little bit at that, whether, for instance, the differences that we saw between individuals could be explained simply by the fact that something was present or not at the beginning. And that's definitely not the only thing. So we had cases in which the same bacteria was present but did not respond to a given food. So there's also other things, probably interactions between different bacteria. There's a lot of interactions in the microbiome that we're only beginning to grasp. So, you know, the way a microbe behaves might be very dependent on whether other microbes are present or not in that particular individual. And that's something that, you know, it's gonna take a lot of experiments to look at. So I think it was, and I was again, was asking about the interactions between foods. That's simply obviously something that's gonna be also very, very important. So on one hand, the interactions between the bacteria but also the interactions between the foods. But, you know, here we did 3,000 in vitro fermentation. So you can imagine how many vitro fermentation would have to be done to serve the interactions between all of these foods. So that's, you know, work for a generation, not for a project. Right, for an army of graduate students or something. Yeah, long way. No, no, no, no. That's so long. To take care of our graduate students. Very important. Thank you, Pilar. Just to close these first rounds of questions, Jose Angel, we've talked about obesity, nutrition, and microbiota. But worry about other non-communicable diseases, how these diseases can benefit for these approaches of personalized nutrition approaches. No, no. I think it's running. Ah! I hope. Don't worry about that. Okay. Okay. You know, there are many diseases included in this classification of non-communicable diseases. You know, an approach of personalized nutrition regarding, for example, diabetes. Could be very, very, very important because of the variability also in the different people that respond to different treatments. But also, just thinking about the use of the gut microbiome also in our strategy of personalized nutrition, it was thinking amazing about the results we have about celiac disease. With children, it's incredible because we have not submitted yet the results to be published, but we have found that celiac disease children metabolize the foods in a different way that regular children and also compared with obese children and those with allergy to cow's milk. Something that we have found is quite important is that people with children with celiac disease, their gut microbiota is not able to ferment to extract the zinc element from the food. And this is very important and very relevant because zinc modulates the immune system and something that is not working properly in this kind of chip thing is the immune system. So we need to look at strategies to modify this microbiota in order to allow them to extract zinc or maybe a zinc supplement could be very interesting for these children because in order to try to perform these modifications. I think we are opening new doors to the approaches of this kind of personalized nutrition applied to different pathologies including this non-communicable diseases. Actually, in the results, in some of the results we observed a very clear cluster with metagenomic data in celiac disease children. They were completely, they have a completely different microbiota composition. So that's really interesting. Yeah, because at the end it's not just the metabolic behavior of that microbiota. So the interaction with the immune system in the gut directly and the modification they have. So more experiments must be performed on this way but I think this is a clear way to perform the future of research applied to personalized nutrition. Thank you very much, Jose Angel. With this question we end this first round of questions. Now we're gonna start with the Stanford Health Projects with work a lot, with achieve objective. We have work in different challenges. But Fabio, what are the lessons learned through all these projects? I think the first lessons was that it's very hard to recruit people to nutritional intervention. This is a focal point because they are the principal actor of this kind of studies. Observational study are more easy to perform but in this case the help of participants is very important. And so I think the best way to obtain participation and motivation of normal people to participate is to inform people. I think the one, of course our nutritional intervention starting during the COVID pandemic, this is a first problem. But I know that if people is more informed about the importance of gut microbiota and in general of health issues is motivated to participate in this kind of story. Of course our efforts in particular of the field staff were awarded, we know that even if the intervention finished some months ago, there is a group of participants that are still using our app, the iDiet app. And this is a good point. Something important to keep in mind is that it's not also that it's difficult to recruit people. It's also very difficult to define what is normal people or healthy people because of more than 600 adults that we were recruiting. Okay, your health status and say, no, I'm healthy. You are not healthy. More than 600 people just to take 200 for the intervention. So all the people is taking medications or suffer any kind of pain or whatever. So we need to modify our mind about what is normal and normal situation. Yes, this complex question and challenge. Another point you just mentioned the pillar is that we have a huge way to understand the interaction between microbiota and nutrition because we are actually, I was thinking that when we start the project, we were working with around 1,000 species or microorganism in the metabolic reconstruction. Now two months ago, they submitted the group of INS-TLA 8,000 metabolic reconstruction in the cat microbiota. So what is the next step you think to integrate the knowledge of microbiota in personalized nutrition or to be more aware of the advances in this topic? Well, I think it's a very, very complicated issue. Right now we have a lot of results that we've gotten from these years of work and I think we need more time actually to look at them and to understand all of these results. I don't think these are things that are as directly translatable as one would want to. There's a lot of very complicated interactions there to look at and to try to understand. We also see, for instance, in the case of cooking methods, the results are not straightforward. We have a great deal of inter-individual variability. So I think we're gonna need to look at many more individuals to try to understand the patterns. But again, that's a lot of work. And then of course there's all of the computational work to integrate that into metabolic networks, et cetera. I think one thing that might be important in the future is maybe to start thinking that the gut microbiome is something that we need to monitor more or less regularly like we monitor many other things about our health so that we have that data for people and we can integrate that into our general picture of their health and their metabolism. We are not used to that right now. Yeah, of course. But I think we're at a point where that could start to be done because even if maybe right now we cannot yet really use all that information in its full extent, but we will have that information for that person, what was their microbiome at 30 or at 40 or when that person gets older, we know for instance that with aging there is a lot of changes in the microbiome that are detrimental. So if we have their sequences when they were young, we know what to aim at, you know? No, in fact, in this way, I think we should give clear instructions to clinicians to use this kind of information and then clinicians should convince the politicians to use this strategy. And I think this is the hardest way because in order to know the cost of the analysis, they are decreasing day by day, but you have a cost and you need to repeat them along the time. So we think it's clear to extract information that clinicians at hospitals or primary care units or whatever to use this information also for nutritionists. Yeah, this is a major point in my opinion and it also happens in other diseases like cancer. We are talking about personalized medicine, but we need to create the infrastructures and the equipment to make it possible. So thank you very much. Jose-Angelo, yes to end with this round of questions. Fabio has also talked about the intervention trials. You have a lot of experience with this. You have suffered a lot in these trials, which are the main challenges that you found in this process. And a limitation we have to carry out this intervention trials. So it's not easy. I mean, for the people, the people usually respect if you give them some instructions in face by face, but following some rules, some modification throughout is not easy to follow them because of they say, okay, this is artificial intelligence. You know that right now everything is around artificial intelligence, I say, I'm not sure if trusting on this artificial intelligence could be enough. Although they know that research is below this recommendation, it's not easy. But also, in the case of the intervention per se, it was not easy to tell them, okay, for example, we are here this week to take your FICAL samples to analyze. Please you have these parts of the day to give our samples and one of our people in the field working, they receive FICAL samples during the lunch break. You can imagine in the restaurant, here you are my FICAL sample, put in the table and move out. This is something more serious for the people you know. It's not easy. And you need to be very clear when you need the things to, it's difficult, it's difficult. It's also personalized the research. Yeah, not only nutrition. I don't know if we have questions in the audience for this round of questions. I know the online question is completely full. Anonymous is writing a lot. Working a lot. We can answer. I agree with all. I wonder who wants to answer. You can see, all these smart technologies, for example, the apps are available to the public. In our case, no, in our case, we are working finishing more the commercial application. Probably in the coming months will be available to be used. Although we need to let the people know that we are going to prepare different modifications of the app depending on different pathologies because something is for plain people, healthy people and something applied for pathologies because of regular people could be more or less interested on their health. But those that will use more this personalized nutrition strategy are people that is unhealthy and have some pathologies and they want to be healthy. So we are going to work on this in the coming months also to prepare different modifications. Anonymous is not only doing questions, but also making observations to the debate that are more observation than questions. Okay, Mary, go ahead. That in terms of modulating the gut and linking it to a health outcome is where this kind of data will become so important because then we can see that through intervention you can modulate the gut and then you can link that to a health outcome so that will be very powerful data. I just wondered about compliance and how it's a difficult protocol, especially for children providing fecal samples and that's very challenging. So congratulations that you were, whoever the poor people that were out collecting the samples were. It's very difficult and I know that kind of work. There is no nine to five aspect of it. It's very challenging. But how do you measure compliance in your studies and was that a big issue? You can imagine you said with children, for example, how difficult it is. I really acknowledge the work of our crazy pediatricians, you know, the crazy Greek pediatricians. It's horrible because it is not a person that use the app and provide the samples. You need to fight against your children and say, no, the food you want to eat is not so healthy. We need to match this. And of course, the main work is to train the parents to say no, no, you need to have clear mind and what is better for your children and you need to modify little by little the food intake and the kind of food they are taking in order to take this. Don't worry about the complaints, the modifications of the diet. For example, something that we did in the application is, okay, here you are, the menu you need to use in this week. But if you don't follow this menu, you only need to use the app and modify the food you are taking. So the app will recalculate the menu for the rest of the week just in order to check these complaints. So the app trained to modify this because we know that nobody's going to follow 100% of the diet you are using and what you want is to use, to follow the recommendations. Not 100%, but at least to follow because of the app, at the end, is just something to train the people, to teach the people how they need to feed themselves and they'll get the microwave. Thank you. More questions? If for a mononimus. In order to allow him or her to understand you. Thank you. And for the eye diet to prove its value. Then sooner or later we'll be adapted by the medical professionals and from the medical societies. And then you don't have to wait for the public sector, the public officers to give special instructions and to give the money for this to be applied to the whole population. It's the private sector. I mean that when something is proved that it has a real value, then people will start asking that. And then I'm sure that labs who analyze the microbiome will flourish in every country and people will ask for their microbiome to be analyzed and to do a special diet. I mean, that's at least what happens in Greece. First is the private sector that comes and then the public sector follows. Sure, and at least we need to be able to give clear data to clinicians or to the customers about the information of the gut microbiota because of the composition of the gut microbiota per se is nothing for a clinician or even for a researcher. You need to go deeper into what happens with that. What information can you start from that? And as you said, first probably we need to push on the private sector just to allow them to learn that they can have money from there. And then probably in the public sector, the responsible people that manage the funding will see that this is something good. But you know, it's hard to modify this. Thank you, Jose Angel. Any more question? Okay, so let's go to the final round of questions where we're gonna talk about the future and recommendation. Jose Angel just talked about the difficulty to convince parents to follow the diet. What are the difficulties in the addition of two healthy diets? What are the challenges that we must overcome to follow the recommendations? Yes, also in this case, information is the first point. We have seen that also for other problems like for example, cigarette smoking campaign where the informative campaign were important to reduce this problem. In my experience with childhood obesity, we obtained a good result. For example, in some school, we worked with children and adolescents. At their school, we were able to modify the menu of the school canteen. In some cases, we were able to substitute the use of snack at the school with fresh fruit and vegetables. But this was a very hard work thanks to intervention focus group meeting with different level, with children, with adolescents, their parent, with their teachers, also involving the stakeholders in this field. So information is the first step. The second step is also represented by the food industry because we know that in Europe, there is an high consumption of ultra-processed food. About 50% of the daily intake, calories intake in children and adolescents is represented by ultra-processed food. And so it will be important that food processing may reduce the content of salt, fat, sugar in processed food, specifically in food targeted for children. And the last point is to make available all these instruments and all food, all healthy food to all, popular to all consumers. Okay. I think we should not, I mean, the food industry is not the devil, you know, but we need to keep in mind that they are there, they are private companies to make money, okay? Not to kill us, yeah. But keeping this in mind, we need to think that we need to train the children when they are newborns almost on the kind of food they are eating because we give them especially sugary milks, for example, or quite sweet, they will train and you know the perception level they have of sweeteners will be higher. So we need to take care because if we give so sweet foods when they are newborns, they will eat a lot of sugars when they are adults. So we need to change our mind about this because it's not just food composition, but also the kind of foods or the ingredients we use during cooking. So we need to keep change our change of mind. Yes. Thank you, Jose Angel. Pilar, anything to add about how to incorporate of the obstacle to integrate microbiome data into personalized nutrition? Well, I guess the education aspect is also very important here. I think a lot of people nowadays do have some idea about the human microbiome. It's actually been pretty fast, amazingly fast how this has grown into the population. The perception of bacteria has changed. Now, more and more people realize that bacteria can have a positive role for health. But of course, often what people get from food industries from commercials about probiotics, probiotics, it's pretty simplistic. So I think it's important also that people have more scientific education about it to be able to judge what is being offered to them. I think this is really important in the previous events we have in San Sebastian, my university. I was surprised because many of the attendants to the meeting didn't know anything about microbiota. They were very surprised with the impact of microbiota in the HALDA. So many students, colleagues that attended the meeting was really surprised. So I think this scientific education is really important to overcome this obstacle. Jose Angel, just to finish this discussion, there's a talk, what are the biggest learning and recommendations for future research or future European funded projects? Which is your experience leading a stance for health? Very important. Fun, right? Yeah, fun. He enjoy a lot. Yeah, yeah. The first thing, don't be the coordinator. That's the key. But removing that part that in order to approach the research, in the case of European projects, that is a top-down approach and you have the challenges there and the topics that you need to include all the things that are requested by the European Commission, and you usually look for the best partners that fit on the topic you are applying for. But just in this case for researchers, just think not on the best partners for this. I mean, those that fit well, that look for those that are going to work in the best manner in the best approach of this, because sometimes you will earn time that you are going, if not wasting the performing the different tasks you have there. Is, I think this is quite important. And also try to strengthen the dissemination of the results because it's not just to publish papers or put in a public repository the data you have. You need to disseminate and to reach the normal people. It's quite important as you said in San Sebastian or whatever. Anytime we have an open session with people, the people need to know what we are doing with their money because we are using their money. And not just is how we are advancing because if not, nobody will know that. In fact, we are crazy about the low, I mean, of course, I apologize, the low knowledge about this application for nutrition or whatever in clinicians. It's incredible. It doesn't matter talking about children or talking about cancer or with oncologists or whatever. It's the knowledge is quite low and the integration of the different units is not existing. It's quite difficult. So we need to push also in the clinic sector in the health sector to work together in order to develop this to research but also to treat the people. I think it's quite important. Thank you, Jose Angel. I just to say he was a really good coordinator in the project. And I have to say that when we start talking at the beginning of the project and preparing the proposal, Jose Angel say, we are gonna grow as in our research with this project. And I have to say after four, five years, myself at least, I could grow with this impressive set of researchers and colleagues. So thank you very much, Jose Angel, for all your work and your leadership in this project. And now, I don't know if we've got time. Anonymous. Anonymous was writing something. More questions. People in the audience has any. Yes, for example, you know that Carlos, not anonymous, okay, this time said, more long term studies and collaboration across disciplines. We were talking about, it's very important. You know, as Pilar said before, we need more long term studies and also take repeated analysis of the gut microbiology to check what's happening there, what we have been modifying. What is happening there? I think it's very important and also the collaboration across disciplines is mandatory. This is the real strength we will have, if not, okay, another project, another whatever, but we are not going to advance to really press the population. I agree, Fabio. Yes, yes. The only key is to cooperate and also to create net with other researchers in the same field, also to add opportunity, add ready ideas. It's not lost the work we've done in these years. And something we learned. Also, collaboration across disciplines and also different kind of research participants, because of, in our case, the industry was passing us to obtain the results and to do things with a different point of view, which is the application. And we need to keep in mind that as researchers, the data, the knowledge we obtain should be applied for something. And there, the companies are very important, irrespective if they are from the health sector, the food sector, or whatever. They need to be able to apply what we are preparing, if not, this won't be, it's just knowledge. We need companies help us to make more objective or the impact of our research. So this is also important. But I think I want to emphasize also the richness of different disciplines in the projects. I was really surprised in my case, for example, in the development of the algorithm, the contribution of different partners, not only scientific, like Jose Angel Pilar, but also Veronica, only with the E-Diet, she helped us a lot to move further and to not get stuck with the complication found in the projects. Camila? Yeah, I have a question. Yeah, can you hear me? So in terms of the research, like what do you think it would have been nice to have that would have been helpful to do the research in terms of, I don't know, some other partners, maybe in the development of local governments for the implementation of this, or like more hospitals, more, I don't know, what do you think it would have been, what addition would have been nice to have to make all the study a little bit easier and then the impact to be a little bit even more impactful? Yeah, first, more time to analyze data. Because of you draft a project, knowing what you want to do, okay? But the huge amount of data you are producing and you are able to extract information from that, I know we are going to be working on this project at least for three or four more years, at least, publishing, extracting data and re-analysing the data and also sharing and other researchers will analyze the data from different point of views because it's so big, it's so big and the amount of information and relationships you have that with time, you extract more info from them. So I think that time is some of the keys of the thing. Yeah, I agree, I mean, I think in the case of the inventory fermentation analysis, I mean, of course we could have done more but I don't think it would be reasonable either to think of doing more in the context of a single project. I think it's just that it's the first time that this has been done to this large scale. I mean, before our study, there were just, you could count with the fingers of one hand that the type of similar works that had been published. Some of them by us, actually. But so it's really something that is very novel. I could say I would have liked to analyze 20 people instead of three, I would have gotten much better results but it's not reasonable. It's just we're starting something that needs to go on for a long time. It has to be repeated by other people. It has to be extended in many ways but honestly, I don't think it would have been reasonable to say we're gonna do all of that in the context of one project. Even with the knowledge we have now, I would like to have more clinicians involved there just to help us to extract information, useful information to be applied directly in the daily clinic practice. I know, I have learned a lot about this, about how can we exchange, use the same language. I mean, the research language and the clinician language in order to use this information is extremely important and I know that more clinicians are more time to talk with them and to extract information could be also very important. I think something that we should probably start thinking about maybe not only among us but with other people that work on similar things is what Costas was saying actually about not starting to put together some kind of guidelines even if they're very simple but start the process and keep refining them with time but right now there's a few things maybe not many but a few things that we can definitely put on paper you know, black over white, we think this is like this and then you know, with time... It's a way to start, yes. Yeah, exactly, with time with more people involved and more people thinking about it make them more and more sophisticated but we could probably start at least getting together and starting to think about it. Yeah, thank you Pilar. Bianca? Yeah, you raised the ball Jose with more dissemination, communication and now that Camilla asked what's missing I wanted to say something what I feel now after the event we had in South Sebastian what is really missing an event like the one we had dedicated to regular people who have no idea about personalized nutrition who don't know how easy it is to have some small tricks that you can implement at home that you can help your microbiota because it was really amazing to be there with them to cook, I don't know if... It can be called cooking what Veronica and I did but... I don't know how to interpret that, Bianca. We tried. But it was amazing to really see their faces and to realize that there is so little knowledge I mean in the online world you see a lot of information about healthy diets, about what you should eat but at the end of the day it's so simple and this event that we had has proven us that this is also very important to really translate the science to the plate and to talk to normal people about this and I think it also helps as a boomerang in developing the app in helping, shaping the results so it was very unfortunate that COVID stopped us to do more but I think this is something that future projects can keep in mind the importance of having events dedicated to the final customers of the results that will come at the end. In that event we have a round table and one of the participants was a tough chef in the Basque country which is an area, a popular area where you eat very well in Spain and after in our university we have a gastronomic society which is something very typical in the Basque country where well I'm not going to tell you the story about gastronomic society I can tell you later in the coffee break if you want but every professor in our university can book this gastronomic society and then you can there cook, meet your friends you have like 20-30 positions so we organize an event with students, with master students and undergraduate students and Bernonika and Bianca cooked, I helped them a bit, a bit and also the chef prepared very complicated sources so students preferred the food of Bianca and Bernonika because it was simple, it was simple and easy to cook so it was an important and good experience with this now with Bianca One very short point about what's missing somehow the point of anonymous there about psychology because I'm a parent of a teenager and some weeks ago he told me mom you messed up with me, you made me wrong now I cannot eat so much sugar and sweet things and I'm trying but then what do you do with the kids that go to school and that are surrounded by other kids eating sweets and junk food and KFC and whatever food it's not okay so then I think really it's important to also consider this element it's not just important to know what to eat but how do you educate people to eat what they are supposed to I think it's very important that part because when you are drafting a project you are thinking of what the commission asked about this you have different approaches of course but it's a bit that the last meeting you performed in San Sebastian was at the end of the project maybe we didn't have the COVID pandemic or whatever we performed before this kind of meeting probably we would have more meetings on that side but at least we have in mind that this is functioning very well for future projects we can do this kind of things but we can say that although it's not a meeting we are going to release a book of healthy recipes with all this information and whatever and with the supervision of the nutritional point of view and healthy for the gut microbiome also so we will impact in a different way the people I think I just want to add that I believe that citizen engagement is key in this as you mentioned I think the coming projects like the next generation of projects includes a lot of that it's also very important to change the environment of people to get the better foods and to change the norms talking about the human psychology here and then I think translating science is one of it's always being very complicated between the experts but also it translates science to the general public and well that's what we do at UFIC so if you ever want to go to our website and see more information you can just go there I think Francis you were finalizing this to go to for lunch this is after the this is the chuleta or the ship of the discussion it said after one sort of sentence which is going to be the main actor for driving these chains one sort of sentence ten seconds answer Fabio your first the first actor I think as we said before one actor is not possible it needs communication multi-actor approach is the key okay so after this answer that's it nothing more it's going to be for lunch