Intro (00:09:22) 

Science on the Menu, a podcast by the European Food Safety Authority.

Ed (00:20:15)

Hello and welcome to another episode of Science on the Menu. My name is Ed Bray and I am a Communications Officer at EFSA. And joining me today is Antonio Fernandez Dumont. 

You work Antonio in one of the GMO teams at EFSA. Is that right? 

 Antonio (00:38:11)

That's correct. Hello Ed, I work at the GMO mainly with the focus on food and feed safety aspects of GMOs.

Ed (00:48:03)

Today we’re going to be talking about celiac disease, and it's timely because on May the 16th, around the world, we celebrate Celiac Awareness Day. Let's kick off with the simplest question, but the most important question. What is celiac disease? 

Antonio (01:08:16)

Thank you, Ed. Celiac disease is an inflammatory disease, is a chronic disorder and it derives from gluten consumption.

Ed (01:22:05)

So where do we find gluten? What is it? 

Antonio (01:08:16)

Gluten can be found in some cereals, in particular wheat, rye and barley. But not all cereals contain gluten, for example, Maize or rice do not contain gluten.

Ed (01:38:02)

Could you give us a rough idea of how many people in Europe suffer from celiac disease?

Antonio (01:08:16)

In Europe, at the moment, around 1% of the population suffers from celiac disease. It's quite interesting because of course, to develop celiac disease, you need to be genetically predisposed. And around 50% of the population in Europe might be genetically predisposed, but only 1% suffers from celiac disease. 

It's quite an environmental component that we don't know at the moment what's going on. We have some indications, but not everything is clear on why only 1% of those suffer from celiac disease.

Ed (02:24:19)

It could be a mix of genes, but also a mix of something else that's going on in the environment.

And what does it mean actually to suffer from celiac disease? 

Antonio (02:38:10)

It's a condition mainly involving the gastrointestinal tract, in particular the small intestine and everything that is associated with it, like vomiting, diarrhoea are the conditions of those suffering from celiac disease. And I would say most importantly for children because of the GI tract, it does not function as it should due to the inflammation. It can cause the stop of growing of the children. So, it's quite a serious condition for children. 

Ed (03:12:04)

That is really serious and I understand that actually there isn't a cure for the disease. Is that right?

Antonio (03:19:20)

Exactly. At the moment there is no cure. Only lifelong avoidance of gluten. That means of the cereals containing gluten, such as wheat, avoidance of wheat, barley, and rye. 

Ed (03:35:00)

And how does celiac disease differ from allergies. Is the body reacting in the same way it would to other known allergies. How is it different?

Antonio (03:50:10)

In celiac disease as well as in allergies there is a component of the immune system. It is an immune adverse reaction to foods but it is different as compared to allergies. In the case of allergies, it is a life-threatening condition, which is not the same as for gluten. And in the case of allergies, it involves immunoglobulin E, an antibody. That triggers the release of histamine and the inflammatory response that becomes systemic, which is not the case for celiac disease. 

Ed (04:25:12)

But still, essentially your body as a celiac disease sufferer is identifying the gluten and then triggering a response in the body - that is responding in a way that is harmful to your own body, is that correct?

Antonio (04:44:12)

Exactly. That's correct. But obviously, it's only to those that are genetically predisposed. 

Gluten is a protein that we find in these cereals and it's an excellent source of protein for most of the population that can eat gluten. Gluten is in bread, in pasta and makes these cereals bakeable. But for those individuals that are predisposed, it's a problem. 

Ed (05:17:07)

We've talked about what the disease is, those people that get it, some of the symptoms and the fact that the only way to deal with it is to avoid gluten. 

What about your work? We said that you're in one of the GMO teams at EFSA, why would someone in a GMO team be involved in this issue? And what have you been doing exactly?

Antonio (05:42:22)

One of the roles of EFSA is to perform a risk assessment of new products and within these new products, the unit I'm involved is in one focusing on genetically modified plants. One of the questions in the assessment process is whether or not new proteins in GMOs might cause adverse effects. One of those being celiac disease, for example. 

This is the reason why we focus our evaluations on investigating whether or not these new proteins might cause problems for those people suffering from celiac disease. 

Ed (06:23:21)

And EFSA, along with other research partners, has developed a new tool that will help celiac disease sufferers. Can you tell us more about that?

Antonio (06:36:17)

That's correct. In 2017, we developed for the first time a guidance document with very clear indications, comprehensive analysis on the way to assess this capacity of proteins to trigger celiac disease from GMO plants, as any new proteins. And among that work, we also focused on the potential development of a software using bioinformatic tools and to provide information on the likelihood of these proteins, the capacity to trigger this disease.

This is how we embarked into that activity. And indeed, we released the first software a year ago, and this is already in place now, and applicants are using it for the safety assessment of their products. 

Ed (07:31:05)

In very simple terms, you can insert a numerical value for the protein, and then the tool will be able to scan for it. And the disease sufferer would know that that could be a risk. Is that right? 

Antonio (07:50:09)

Yeah. So how it works, it's publicly available and you will enter the software you can input the amino acid sequence of your protein and you get an output that will be a quantitative numerical factor giving you the likelihood that your protein has to trigger celiac disease.

Ed (08:12:09)

I imagine it took some time to develop this tool. Can you give us an idea of what went into it, what made it possible to develop this tool now? 

Antonio (08:24:24)

Everything has started in 2013 when we launched a procurement, which means EFSA can also ask external contractors to prepare work for us. And this contractor did an excellent review on all different conditions that are not allergy IGE mediated for which we could develop risk assessment tools into our evaluations. 

In that work, celiac disease was the one for which we could find clear cause effects, relationships that could be incorporated into risk assessments. So, we know the cause (gluten) and we know the effects. There is clear information on the pathogenesis of this disease that is not the same for others. And because of that, we were able to define what they mentioned in 2017, the stepwise approach for the risk assessment, and even go a step further and develop a software in this direction.

Ed (09:30:24)

The software is available now already to be used. Are there plans to develop it even further in the future? 

Antonio (09:40:09)

So, it has been there for a year now, more or less. And as I mentioned before, it is the first time a software of this nature is published around the world, and it will have to be updated.

And these updates we just embarked on a new project with the Medical University of Sofia in Bulgaria aiming to improve the current tool, considering the feedback received from stakeholders using it, and also considering the state of the art that has been developed in the last two or three years. So, it will be to incorporate the two aspects.

Ed (10:23:14)

The first in the world. This is really cutting edge in terms of the use of this tool and the capacity that it has. 

We've talked about the tool and what EFSA developed ,etcetera. I'd like to talk about another area, which is an increasing area of research around the microbiome, which has become an area where there is a lot of interest.

I’d like to ask you whether there is a link between celiac disease and the functioning of the microbiome, which is essentially, if I understand well, the microbiome is the environment of the guts, the community, if you like, of bacteria that are in the gut. Is that correct? And what’s going on there in terms of research?

Antonio (11:09:09)

Yeah, that's correct. The microbiome it's key for a normal function of the gut and immune system and we know that dysfunction of the microbiome is involved into chronic diseases, maybe also celiac disease. We don't know exactly which one are these but is very likely to be in both. 

Some of the latest publications have shown some of the peptides, the amino acids sequences in some bacteria mimic those of gluten and there has been some theories or hypotheses whether or not these bacteria might indeed initiate some of the diseases because of these the dysfunction of the microbiome.

Ed (12:00:23)

Is this something that EFSA is looking into right now or something that is out there in research but we are supporting that in some way?

Antonio (12:17:01)

This is quite an interesting topic and there is quite a lot going on at the moment. 

Indeed, EFSA has been investing some resources on seeing how we could incorporate into risk assessment the science that we know at the moment. There has been a release this year of a report. It is a road map for the integration of gastrointestinal microbiomes in risk assessment. And I'm sure we will hear more about it in the coming future.

Still it is too early to incorporate anything in risk assessment, but this is the future to come. 

Ed (12:48:09)

So essentially what would happen in risk assessment would be to see how either a regulated product like an additive or other food safety issues could impact on the microbiome or the microbiome impact in some way on what's going on? Is that right? 

Antonio (13:07:06)

That's correct. How the microbiome will be modified and the gut or the immune system in that sense. Yeah, that's correct. 

Ed (13:19:01)

So, watch this space essentially for the future to see how food safety assessments could evolve in that direction. 

Can I ask you a personal question, Antonio? How you ended up here? How did you get into this area? Both in the GMO team, but also working on this area of celiac disease. 

Antonio (13:38:24)

I am a vet by training, which is a bit weird, but I started as a researcher, always working with allergies and animal models. But animal models are not good models for humans.

Celiac disease I think is teaching us a lot: what is the pathway to follow for other conditions for which we know much less. And this is why we have been mainly focusing on celiac disease, not only on its own, which is a great achievement, but also to enlighten us on how to move for other conditions maybe which are life threatening conditions.

Ed (14:21:17)

For example, someone in my family has a very specific reaction to a type of nut, to Brazil nuts, where they can go into shock. This is what you're talking about. 

And what kind of things could be done there to limit that? Do you think it would be possible even to eradicate allergies in the long term? Or is this too extreme? You're thinking about ways of detecting, etcetera?

Antonio (14:49:19) 

At the moment there are different projects for sure working in this direction to eradicate these diseases. We are not yet there. Eventually, one day maybe it will be possible, and this is one of the ultimate goals of some of these projects to eradicate eventually these diseases. At the moment, it is not possible. 

Ed (15:13:23)

And this work that has been done on celiac disease, you say, could be a first step. 

Antonio (15:18:10) 

Yeah, it could be a first step because it is giving us the pathway to follow also for those diseases. What could be these genetically predisposed conditions? What could be the environmental factors? And gluten is very well defined, the structure that we can better focus our investigation on to then extrapolate those considerations into other molecules or that are more complex. 

Ed (15:44:18)

Can you give us some examples of the kind of environmental factors that might be relevant or important in this? 

Antonio (15:51:03) 

It could be, as we discussed before, the microbiome, it could be infections during your life, it could be where you live, exposure to contaminants.

All this will have an impact on your immune system. And these are the environmental factors we don't exactly know at which moment which ones will drop you into celiac disease, for example, even if you are genetically predisposed, as I said, only 1% develops the disease. 

Ed (16:24:12)

I imagine that could even be the case that for some people they develop it later in life.

Is that possible? Or that even that it changes over time and maybe they suffer less? Is that possible? 

Antonio (16:38:14) 

Exactly that's possible that you develop this later in life because of these environmental factors at that moment you will suffer from those and then trigger the disease. Indeed, yes. This is why you can develop these later in life.

Ed (16:57:19)

One final question to you, Antonio. Is there anything else that you’re working on now, that you could share with us? 

Antonio (17:05:23) 

Yes. For celiac disease, we are also embarking into a project called an Adverse Outcome Pathway. We are working in collaboration with the OECD and it's to bring all the knowledge we have at the moment on celiac disease and describe it in one single document.

That document will help us also to better understand what the key elements are that we need to consider in risk assessment. And again, that one can also bring light on other conditions that are more complex to focus the attention on. So that's the work we are doing now and will finalize by the end of 2024. 

Ed (17:48:22)

I think that's a good moment to wrap this up, Antonio and thanks very much. This tool is obviously a big step forward and let's see how that develops also in other areas.

Thank you very much for joining us today on the podcast. 

Antonio (18:09:18) 

Thanks a lot Ed, very welcome. 

Ed (18:11:09)

And thanks a lot, to all our listeners for joining us. 

You can find out more about the podcast on our website, all the previous episodes. Please check out our social media channels as well where you can find some clips also of the podcast.

But for now, that's all from us. Hope to join you again soon. Thank you and goodbye.