Season 2 Episode 7: A Safer Slice: Can Wheat Be Engineered to Prevent Celiac Disease?

Vanessa:

Welcome to season two of Raising Celiac, a podcast dedicated to raising the standard of education, awareness, and research on celiac disease and related autoimmune conditions.

We have some exciting changes for this season. The Boston Children’s Hospital Celiac Program has teamed up with the Celiac Disease Foundation to expand the reach of our educational podcast. Our goal is simple, to provide education to as many health providers and patient families as possible.

I’m Vanessa Weisbrod, and I’ve started a new role as the Chief Education and Community Engagement Officer at the Celiac Disease Foundation. In every episode you’ll also hear from Janice Arnold, an incredible social worker at Boston Children’s Hospital, who is the voice of our patient stories. Each month on the podcast, we will invite leading experts to dive into a hot topic related to celiac disease and look at how it impacts a patient family, the latest research, and offer suggestions for health providers to manage these complex cases.

Every episode of the Raising Celiac podcast is accredited by the Boston Children’s Hospital Continuing Education Department for physicians, nurses, social workers, dieticians, and psychologists. To claim your credits for listening to today’s episode, please visit dme.childrenshospital.org/raisingceliac. We’ll also drop that link into the show notes. Thank you to the Global Autoimmune Institute and the Celiac Disease Foundation for making this podcast possible. Now, let’s get started with this month’s Raising Celiac patient story.

Janice:

Marcus is 16 years old. He doesn’t have celiac disease, but his mom and older sister do. His family has learned to navigate the gluten-free diet with dedicated kitchen spaces, label-reading, and the constant worry that something might go wrong. Marcus’ pediatrician recommended testing his genes, and sure enough, he carries the HLA-DQ2 gene that puts him at risk. Roughly 30 to 40% of the population carries a genetic risk for celiac disease, but only about 1% develop it. Still, that 1% translates to millions of people worldwide. And while we can’t yet predict who will develop celiac disease, we know that both the amount and duration of exposure to certain gluten proteins called epitopes play a role.

Marcus is thoughtful about what he eats, but he’s not on a gluten-free diet. His family decided to enroll in a long-term study tracking people at risk. They monitor his blood work, keep a food diary, and hope that if signs of celiac start to show they’ll catch it early. But the looming question always remains, is there anything they can do to prevent it?

Vanessa:

That question is exactly what new research aims to answer. A new study from researchers at the University of California Davis and published in the journal Theoretical and Applied Genetics investigated specific changes to the wheat genome, removing a group of alpha-gliadins on chromosome 6D. These are the proteins that contain most of the immunodominant epitopes known to trigger celiac disease.

Janice:

Marcus’s mom recently read an article about this new wheat and cried. For the first time, she saw a future where prevention of celiac disease might be possible, and a future where she and her daughter could eat bread made from this new wheat.

Vanessa:

Researchers don’t know yet if this new wheat is safe for patients with celiac disease. But by deleting these highly immunogenic regions, scientists took a critical first step. The Gli-D2 deletion not only reduced celiac-triggering epitopes, but improved bread-making quality, potentially proving that safer wheat doesn’t have to mean inferior food. We’ll dig into the data and the bigger picture on today’s episode of Raising Celiac.

Today’s episode takes us into the wheat fields and the genetics lab with doctoral student Maria Rottersman from the University of California Davis. Maria is part of a research team led by Dr. Jorge Dubcovsky working on a groundbreaking project to remove harmful gliadin proteins from wheat. This research has the potential to one day reduce the risk of developing celiac disease and improve quality of life for future generations. Welcome, Maria, to Raising Celiac.

Maria:

Thanks for having me.

Vanessa:

So let’s start with the big picture. Researchers at UC Davis may have taken a major step toward making wheat safer for people with celiac disease. Can you walk us through what this breakthrough means and how your team approached the challenge?

Maria:

Yeah, of course. So there’s lots of technical details to the project, so for those who are interested, I’ll invite you to read our scientific publication. But the big idea is that we identified some gene deletions in wheats that might be beneficial for families with celiac disease while actually improving grain quality. So the wheat we developed in these experiments is not celiac-safe, but it could help reduce the burden of celiac disease on the overall population. So we think this discovery is a win-win for both growers and consumers.

Vanessa:

That’s great. So can you give our listeners a simple explanation of how genes are coded and what that means in terms of expression?

Maria:

Sure. So each gene in each organism is encoded in DNA, and then each gene also has an instruction manual for creating a protein. There are many different genes between and within organisms, and there’s also different versions of the same gene, which we call alleles. So my research is about the gluten proteins, and each gluten protein has its own gene. When we look at any given bread-wheat variety, there can be around 80 different gluten genes. So there are many different combinations of alleles that are possible within a given variety. What this all means is that we’re looking at a lot of variation at once in each wheat variety when we study all the different genes that encode gluten proteins.

Vanessa:

Wow, it’s so interesting. So for those of us who are less familiar with wheat science, can you explain what gliadins and glutenins are and how they contribute both to bread-making and to triggering celiac disease in genetically predisposed individuals?

Maria:

Yeah, so glutenins and gliadins are both types of gluten proteins. And when they get wet, the glutenins link to each other and they form a mesh structure. So that’s what makes wheat dough so stretchy and elastic if you’ve ever worked with baking bread, for example. Both glutenins and gliadins have peptide sequences that can trigger celiac disease symptoms, and we call these peptide sequences epitopes. But when we look at the epitopes that induce symptoms in most celiac disease patients, most of the time we’re primarily looking at the gliadins. So one type of gliadin, the alpha-gliadin, accounts for about half of all the celiac disease epitopes in wheat, depending on the variety you’re looking at. So that’s what our paper focuses on, are these alpha-gliadins.

Vanessa:

So as you mentioned, the study focused on deleting gliadins from a specific area of the wheat gemone, chromosome 6D. Why was this particular region targeted and what makes it so significant when it comes to celiac disease?

Maria:

Yeah, so as I mentioned earlier, the alpha-gliadins are some of the worst proteins for triggering celiac immune responses, both in terms of frequency and severity. So we decided to test wheat with deletions in the alpha-gliadin genes first, and the alpha-gliadins happened to all be on chromosome 6 in wheat. So this is where all of our deletions took place.

Vanessa:

Got it. So the Gli-D2 deletion seems to be the standout. It not only removed the most harmful epitopes that trigger immune responses in people with celiac disease but also improved the dough’s strength. How did you discover that combination of benefits?

Maria:

Yeah, so this finding was a bit of a surprise for us because we know that gluten is so important for bread-making quality. So when we saw that wheat with this Gli-D2 deletion had improved quality, we decided to do a little bit more research and dig a little bit deeper and try to figure out why that was. So we found out after doing some analysis of the proteins and where they are in gluten, and we found out that some of the alpha-gliadins that were in the Gli-D2 deletion had these naturally occurring mutations that caused them to interfere with the rest of the gluten structure. So that way, when we had the deletion of these particular proteins, we got stronger and more expansive gluten matrices.

Vanessa:

That’s so interesting. From a public health perspective, this could be transformative. What does reducing immunodominant gluten epitopes mean for efforts to prevent celiac disease at the population level?

Maria:

We know the HLA genes that put people at risk for getting celiac, but we don’t totally understand what determines the onset of the disease in the people with these genes. However, what we do know is that there are a lot of studies that show that when people with the celiac disease-predisposed genes have more exposure to gluten epitopes, the more likely they are to develop celiac disease earlier in life. So if the amount and the duration of gluten exposure is related to when people start getting symptoms of celiac disease, we hope that making a wheat with fewer triggering celiac epitopes could delay or prevent the onset for some at-risk individuals from developing celiac.

Vanessa:

I know as our listeners are hearing you talk about this, a question that many of them are going to have is, is this genetically-modified wheat?

Maria:

Great question. So these lines do not have any foreign DNA, so they’re not considered GMO. The gene deletions we used are very much like the ones you would find in nature. They’re just mutations, and modern technology allows us to see which mutations we’re selecting for and we can make more informed breeding decisions. But the process of actually making the crosses and producing the lines is a conventional one.

Vanessa:

Great. So there is an important caveat here. We don’t know yet if this wheat is safe for people living with celiac disease. Why not? And what kind of research needs to happen before we can even consider the possibility of safe consumption?

Maria:

Yeah. So earlier you’ll remember that we talked about both the glutenins and the gliadins and about how many of these proteins might induce celiac symptoms in patients. So the alpha-gliadins we deleted are just one part of this bigger picture. There’s one specific type of gluten protein. So there’s a lot more work we need to do in terms of eliminating the other proteins and wheat before where we can even hypothesize that this would be safe for people with celiac disease. There’s been a lot of epitopes that scientists have discovered in wheat that are available in scientific literature, and we don’t even know if this list is complete. So even after deleting all these epitopes from wheat, the only way we could find out if we actually made something celiac-safe would be to do some clinical studies. And this is possible, but it will take a lot of time and a lot of resources, and it’ll inform whether our understanding of what triggers celiac disease is correct and complete.

Vanessa:

So your team has talked about this being a first step in a longer-term effort. Can you explain what cleaning the wheat genome means and how you’re using both deletions and gene editing to gradually reduce celiac-triggering proteins?

Maria:

Yeah, so when we identified these alpha-gliadin gene deletions, we deleted around 25 gluten genes, but the total number of gluten genes in a wheat variety is closer to around 80. So taking out 25, 30 of them is a great accomplishment, but we have a long way to go. So, so far, the gene deletions that we’re using are from conventional mutations and conventional breeding, and we’re trying to combine as many of these deletions as possible. But as you can imagine, this is pretty difficult to do when we’re looking at dozens of different gluten genes. So we’re also just taking a look at gene-editing technology to see if it’s possible to knock out these genes faster. This doesn’t necessarily mean that anyone will be eating GMO wheat, but it’ll give us a wheat variety that’ll be helpful for scientists studying celiac disease.

Vanessa:

Great. So looking ahead, the Foundation for Food & Agricultural Research and the Celiac Disease Foundation are co-funding the next phase of your research. What are the main goals of the new stage and what are you most excited to explore?

Maria:

Yeah, so we have plants growing in the field right now that have the same alpha-gliadin deletions that we just studied, combined with several other gliadin gene deletions. So I’m really excited to harvest those this summer and see what grain quality looks like. I’ll be able to mill them and bake bread and do a number of quality analysis tests on the flour. And it’ll be interesting to see as we remove more of these triggering proteins if we start to see effects on flour quality.

Vanessa:

So how long does it take to grow this wheat? Just sort of give our listeners an understanding of start of the planting of it to when you harvest it, how long does that all take?

Maria:

Yeah, so we typically plant before it gets super cold out, so around October, November. This also varies a lot depending on what part of the world you’re in, but here in Davis we typically plant in the fall and then we harvest in the spring or summer. So that means we have about one round of wheat per year, one harvest typically.

Vanessa:

Very cool. So one especially compelling part of your research is that it doesn’t compromise wheat quality. Can you share more about how the Gli-D2 wheat performed in terms of yield, protein content, and bread-making properties?

Maria:

Yeah, so the wheat with the Gli-D2 deletion didn’t have any problems with agronomic quality, so farmers can still grow it and be confident that they’ll get comparable yield and high value, high quality grain that they’re used to. But we also talked about how the Gli-D2 deletion was associated with stronger gluten and better bread-making quality. So we hope that growers will be eager to adopt our lines into the fields considering we see an improvement in our quality and hopefully a reduction in the amount of celiac disease epitopes without having to compromise anything like yields or the timing of when the wheat is harvestable.

Vanessa:

So okay, fully understanding that this is not considered gluten-free celiac-safe bread yet, assuming we get over all of those hurdles, could this have the potential to make gluten-free bread bigger?

Maria:

Yes. So currently this is not gluten-free, right, because we just deleted some of the proteins. But essentially because the ones that we deleted kind of compromise gluten strength, the idea is that if there were some hypothetical gluten protein that didn’t elicit an immune response in folks with celiac disease, that gluten would be stronger and better without the immunogenic alpha-gliadin genes.

Vanessa:

Great. So this is cutting-edge science, but it’s also deeply personal for patients and families affected by celiac disease. What message do you hope this research sends to the celiac community?

Maria:

I really want to express my gratitude for all the support we’ve gotten from the celiac community, especially the Celiac Disease Foundation, especially at a time when there’s so much information available to us and it can be hard to decipher what to trust and when you hear things, whether to believe them. So I just really appreciate everyone in the community being such a powerful ally to science and listening to the research. And our research would not be possible without your support, so thank you.

Vanessa:

We are very happy to be a part of it. And I know that this is just such an exciting time for the celiac community. We’re here saying that maybe we have a potential treatment in our future and potentially safer wheat. So we’re very grateful for all your work that’s happening in the lab out there.

To end, what does success look like to you in this work, whether it’s prevention, safer wheat, or new food products? Where do you hope that this research leads in five or 10 years?

Maria:

Yeah, so I’m kind of on the science side and I get to see a lot of cool things happen in the lab, but I also know that applying our work so that it actually can help people is an entire other endeavor. But since we already have the Gli-D2 deletion lines and we are seeing positive effects on bread-making quality and we aren’t seeing any negative consequences on agronomic quality, I would love to see these varieties more widely incorporated into fields and foods across the United States. So this is a deletion that different wheat producers around the country could incorporate into the varieties that they like to grow. And this would be the ultimate test of whether our lines actually can help reduce the prevalence of celiac disease at a population level. And I’m cautiously optimistic for the outcome of our future work.

Vanessa:

Well, we can’t wait to see the results of this next phase of the project and what this leads to in our food community.

Maria, this has been such an amazing discussion, and we are so truly grateful for all of the incredible work that you’re doing. And personally, I can’t wait to see where all of this research leads us. So now let’s take a break and find out where our patient is today.

Janice:

Today, Marcus is a junior in high school and getting ready to apply to college, running track, and thinking about studying biology. He still doesn’t have celiac disease, but his family keeps up with regular screenings and follows the latest research closely. Marcus says he feels lucky to have early knowledge of his risk. “Knowing I’m at risk doesn’t scare me anymore,” he told us. “It just means I get to be part of something bigger, maybe even part of the generation that helps change the story for celiac disease.”

Vanessa:

And now a word from the Global Autoimmune Institute.

Speaker 4:

The Global Autoimmune Institute works to empower solutions in the diagnosis and treatment of autoimmune diseases through research, education, and awareness while supporting multidisciplinary approaches to health. We are thrilled to support the production of this educational podcast.

Vanessa:

Thank you for listening to this episode of Raising Celiac. A special thanks to the generous contributions from the Global Autoimmune Institute to make this podcast possible.

A reminder to all physicians, nurses, social workers, dietitians, and psychologists, to claim your continuing education credits for listening to today’s episode, please visit dme.childrenshospital.org/raisingceliac. If you like what you heard, be sure to write a review, like and subscribe wherever you get your podcasts. For more information, check us out on social at @BostonChildrensCeliac on TikTok or @celiackidsconnection on Instagram. Have a great month.

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