Living with celiac disease, and managing a gluten-free lifestyle, involves navigating a bounty of information and making numerous decisions every day. With all the breathless media coverage of research updates and lifestyle advice, it can be easy to lose track of the big picture when it comes to celiac disease treatment and research.
So we asked three celiac disease experts — two top doctors and the director of the leading advocacy group in the United States — to answer a few questions about where celiac disease management is right now, and where it might be headed. Their responses (condensed and edited for clarity) appear below.
Gluten-Free Living: What have we learned about the causes and biology of celiac disease in recent years? How might these discoveries lead to advances in treatment or prevention?
Alessio Fasano, MD, gastroenterologist and director of the Center for Celiac Research and Treatment, Massachusetts General Hospital: For many years, we’ve known a great deal about how people develop celiac disease. We were convinced we really had a grasp of the entire story. The two ingredients that were considered necessary and sufficient were a genetic predisposition, and an environmental trigger that’s mismanaged by the immune system, which is gluten.
What we’ve learned in the last few years is that genetics and environment are absolutely necessary, but not sufficient, to explain who gets celiac disease. We saw things that were at odds with that premise. In identical twins, with identical genes, who ate the same stuff, one twin would develop celiac disease and the other would not in 25 percent of cases. How do you explain that?
In the last 10 to 15 years, we learned that there are three other elements: a gut that leaks, allowing gluten to interact with the immune system; an immune system that’s hyperbelligerent, continuing to fight when it’s not necessary; and a very different microbiome, the ecosystem of the gut, between people with and without celiac disease.
These five elements offer treatment and prevention opportunities that we didn’t have before. Except for genetics, they’re all fair targets to change the destiny of people with celiac disease.
Prevention would be the holy grail, and that’s what we’re looking at in this megastudy called CDGEMM (Celiac Disease, Genomic, Environmental, Microbiome and Metabolomic Study), where we’re following infants since birth when someone in their family has celiac disease. We follow everything about these kids. We’re asking why some take a wrong turn and develop celiac disease, while others do not. What kind of changes happen before the storm is on their doorstep?
Daniel A. Leffler, MD, gastroenterologist and associate professor of medicine, Harvard Medical School: I think our better understanding of celiac disease has allowed us to see that there’s a need for therapies. It’s really more about the clinical picture of the disease, rather than the scientific background.
That being said, I think there are areas where science has helped us attempt to make really safe, targeted therapeutics for celiac disease, even though they’re not really hitting any part of the disease we didn’t know about before.
I think you can group celiac disease therapies into three main groups. One is things that try to detoxify or protect you from gluten. These would be largely glutenase enzymes, but other things have been tried, including gluten binders. Second, there are drugs that prevent gluten from interacting with the immune system in the intestinal wall. And the third category is drugs that try to turn off the abnormal immune response to gluten.
Our improved scientific understanding has suggested ways to target those three parts of the pathogenesis of celiac disease to create an effective therapy, even though we’ve known that those three things are important for a long time.
Marilyn Grunzweig Geller, chief executive officer, Celiac Disease Foundation: As research continues to prove that a gluten-free diet is not a “cure” for celiac disease as was once thought, the case for investing in celiac disease research — both to create new treatments, and to find ways to prevent it — becomes more compelling.
As more physicians learn and accept that patients with celiac disease cannot be written off with “just go on a gluten-free diet”, there should be a corresponding increase in diagnosis with a potential patient base attractive to biopharmaceutical investment to bring therapeutics to market.
GFL: What have we learned about the causes and biology of non-celiac gluten sensitivity in recent years?
Fasano: Not much. We know that besides celiac disease, there are other forms of gluten reactions, which we thought was not the case until the recent past. This includes non-celiac gluten sensitivity.
Some of the steps in the disease process seem to be the same as in celiac disease. You have to be exposed to gluten, it’s only partially digested, there’s gut permeability, and the immune system reacts to it. What comes next is very nebulous for non-celiac gluten sensitivity.
There’s a 30-year difference in science between the two conditions, and that gap can be closed once we have a better understanding of how to define non-celiac gluten sensitivity and what kind of diagnostic tests we can use.
Leffler: Unlike celiac disease, non-celiac gluten sensitivity is just not a well-defined condition. There are no clear biomarkers; there’s no clear genetic marker — yet it’s real. I see it in my patients.
I think the likelihood is that it’s not one disorder. It’s likely a combination of different disorders in different people that lead to significant symptoms when people get exposed to gluten. From a therapeutic perspective, it may be significantly more challenging than celiac disease because we don’t have the same scientific understanding yet.
I think a lot more foundational work has to be done before we get to medications for non-celiac gluten sensitivity.
GFL: What, in your view, are the most promising recent developments in treatments to reduce the effects of gluten exposure in celiac patients?
Fasano: Unfortunately, we have very little for exposure after the fact. If you’re exposed and have symptoms, the only thing you can do is go through the storm and wait for the inflammation to go away.
There are much more promising developments in terms of protection if you find yourself in a situation where the risk of cross-contamination is higher. There are three or four possible pathways that have been explored in clinical trials: drugs for gut permeability, using enzymes to completely digest gluten, blocking the enzyme that activates gluten to be seen by the immune system, and immunosuppressants. These could all help prevent a reaction in cases of cross-contamination, a safety net if you wish.
Leffler: Drug development is such a tricky process that it’s always hard to predict what’s further along. There’s larazotide, which appears to work on some level by preventing gluten entry into the intestine. That should enter a phase 3 trial in the near future, which would clearly make it the front-runner. But it’s the lone drug in its class.
On the other hand, you have things like glutenase enzymes, where there’s a couple of drugs in different phases of development. There’s a lot of experience with those, and a lot of belief that they should be safe and effective, yet none of them is actually in phase 3.
And then there are some of the potentially more transformative types of therapies, ones that try to reset the immune system, that are in phase 2 somewhere. I think you can make an argument for any one of those classes being a front-runner in some regard.
Geller: There are a number of potential celiac disease treatments in the pipeline. While most are in preclinical development or phase 1, ImmusanT is currently in phase 2, Provention Bio and ImmunogenX are heading in to phase 2, and Innovate Biopharmaceuticals [larazotide] is heading into phase 3.
GFL: Gluten-free food options have grown enormously in recent years, supported by many people without celiac disease adopting gluten-free and reduced-gluten diets. Do you think this development has led to improved quality of life for people with celiac disease?
Fasano: I can tell you that there have been a lot of positive outcomes from this gluten-free frenzy, but of course they come at a price. Twenty years ago, if you were a celiac, you had to go to the special health-food store. Your options were limited to three or four items whose palatability was questionable, with the prices astronomically high.
Now you have a wealth of products everywhere, very palatable, much more affordable. That was simply unimaginable before. But people who are very careful, and people who are reckless, have jumped on this business opportunity.
Imagine if you go to a restaurant as a celiac and say you have to go gluten-free because you have a condition, and a half hour before, they’ve served someone who said, “I want a gluten-free menu, and bring me a beer.” This fuels the sense of a fad diet, and people may take this very lightly and not use the proper stringency in serving you.
Leffler: I think it’s been a net positive for sure. Having celiac disease today is much more manageable on some level than it was 10 or 20 years ago. The costs of gluten-free foods haven’t really dropped much, but certainly the variety and availability have increased, and the quality has probably increased.
At the same time, we know that it has also led to sort of an erosion of a feeling of the seriousness of the condition. You go to restaurants and see people order gluten-free, but then still have bites of their roll. It leads to a lot of confusion.
And it hasn’t addressed what’s in many ways the biggest issue for people with celiac disease, which is these small cross-contamination gluten exposures in restaurants. Yes, it’s easier to go the supermarket and go shopping for tasty foods. But I’m not sure that’s made the celiac community healthier. We still see a lot of people for whom these small, unavoidable contaminations are leading to ongoing symptoms and an inability to control their celiac disease well.
Geller: Mostly yes. Certainly the availability of gluten-free foods in the market, and the FDA labeling rule for these products, have been life-changing for people with celiac disease. In 2009, I was ordering gluten-free bread from Colorado and paying exorbitant shipping fees just so my son could have sandwiches that looked similar to his classmates’. Dining out was more difficult then too, as no restaurant offered gluten-free options on their menu.
However, because of the gluten-free fad, we have seen a backlash in the public’s and restaurant servers’ acceptance of the seriousness of celiac disease — what can be so hard about eating gluten-free if everyone is? And when you dig deeper and ask questions about those gluten-free options, it turns out that while the meal may have been prepared without gluten-containing ingredients, that meal has been contaminated through cross-contact in many ways.
So while quality of life has improved due to greater choice of foods and better opportunities to dine out, most people with celiac disease still face daily the stress of accidentally ingesting gluten and all of the horrible symptoms that follow.
GFL: How do you guide celiac patients to adopt the proper precautions to avoid gluten exposure, without those precautions going too far?
Fasano: There are two breeds of patient that come to our clinic. One is those who don’t really appreciate the importance of a gluten-free diet, who think that once in a while, you can make an exception. Much more common is the attitude of putting yourself in a bubble, being so paranoid that you don’t live a life anymore. They don’t travel anymore, they don’t go out, they don’t let their kids go to camp or sleepovers.
Both attitudes are inappropriate. Ultimately, we’re trying to implement a treatment that preserves the patient’s quality of life. Once you have learned the do’s and don’ts, and you know how to navigate a gluten-free diet, the intent is that you lead a normal life. That’s what we communicate to patients. Ultimately, if everything works well, you won’t be distinguishable from anyone else. Your symptoms are gone, your autoantibodies are gone, your intestinal biopsy shows that it’s healed. And if you don’t tell me that you’re a celiac, I can’t tell.
Leffler: I have that conversation quite frequently with all my patients. We want to strike that balance between being adequately vigilant, but not neurotic. In the end, we want people to have a good quality of life. It’s not a net gain to be miserable but have great control of your celiac disease.
Unfortunately, one of the issues is that because we don’t have great tools for assessment and monitoring, we treat a gluten-free diet as a one-size-fits-all therapy, where we tell everyone to be as strict as possible — even though we know that some people can probably do fine with small amounts of gluten exposure. We just don’t know who they are. And some people, no matter how strict they are, will probably never be able to get full disease control.
This is one reason why I think there’s a real need for celiac disease monitoring and follow-up. For example, we tell people to try eating oats and see how they do. I worry about people who over-restrict, in some ways, just as much as I worry about people who aren’t careful enough.
Geller: Label reading and asking questions are your two best tools in avoiding gluten exposure. If you’re sharing a kitchen with others who do not eat gluten-free, use your own toaster, cutting board, colander, and cleaning sponges, and do not share condiments that have been exposed to gluten. For social events, offer to bring a gluten-free dish if you’re not sure the host understands how to avoid cross-contact with gluten.
And my personal advice is what I call the pre-eat and post-eat. If you don’t think you’ll be able to eat safely at an event, and cannot bring your own food or snacks, make sure to eat a substantial gluten-free meal before and then again after the event if you’re still hungry. While it may feel unfair that you cannot enjoy the food at an event, there’s no need to punish yourself by going without food altogether. In fact, one of my son’s favorite memories is our In-N-Out Burger post-party runs — protein-style, of course.