Unless you have been living on a remote island somewhere with no connection to social or mass media, you’ve undoubtedly heard about “going gluten free”. You’re also probably familiar with, especially if you’ve tried the diet, the controversy over whether the need to be gluten free is real or not. Well, it is. Maybe not for all, but for some, it is a necessity for a healthy life.
Gluten is a combination of gliadin and glutenin proteins in wheat and wheat-related plants like rye and barley. These proteins give bread its delectable chewiness but are also the reason for digestive and even cognitive problems related to Celiac Disease (CD). In particular, the gliadin protein of gluten is responsible for CD, an immune-mediated disease that leads to leaky gut, malabsorption, and chronic digestive issues.
Celiac Disease Destroys the Gut
Every function of every cell in your body is immaculately designed. It was developed over thousands of years to do just exactly what it does. Until it doesn’t. Modern lifestyles and environments have induced changes in cellular function in unimaginable ways, often to the detriment of the human body. CD is one such manifestation of the problems with modern agriculture, namely due to wheat.
When something that is foreign to the intestine is found, the tight junctions that hold the intestinal cells together come apart (think of it as really strong Velcro that keeps particles in or out). Zonulin is the trigger molecule that is released when a misfit particle is noticed. Zonulin incites a flash flood by telling the tight junctions to open enough for water to flood the intestines and wash away the unwanted debris. The junctions then reseal and zonulin is no longer released. This is a natural response to parasites, bacteria, and yeasts,1 but what happens when zonulin is present in excess?
Leaky gut happens. Leaky gut, officially known as intestinal permeability, is one of the major manifestations of Celiac Disease, and it happens in response to gliadin. The presence of gliadin in the intestine has been shown to trigger the release of zonulin. In most situations, this is not a terrible thing. However, for those that have an overexpression of the zonulin receptor, this can be catastrophic.
Zonulin and its receptor are like a lock and key mechanism, where zonulin is the key and the receptor is the lock to each tight junction. Now it’s okay if you have a lot of locks with very few keys, but once you start adding more keys, the tight junctions are going to start unlocking and the intestinal junctions are going to start opening up. This means that large particles, like gliadin are able to flow out of the intestines and into the blood circulation.
Studies have shown that individuals with CD just happen to have more of those receptors, or locks. So eating a lot of gluten will produce excess gliadin proteins and more zonulin keys that unlock the intestinal barriers. This is why leaky gut is so common in people with CD.2
Gluten also signals intestinal cells to secrete a compound that tells the immune system to attack your body. Gluten actually tricks your body into attacking and killing off your intestinal cells. Your intestines are where the majority of your food breakdown takes place and where nutrients are absorbed. So damaged intestinal cells often lead to malabsorption, and the more gluten that’s around, the more cellular damage is being done.3
When gliadin gets outside the intestinal system, these damaged intestinal cells release an enzyme called tissue transglutaminase (tTG), which attempts to break down the gliadin fragment (deamination), modifying the protein in such a way that body doesn’t even recognize it as food. It is now considered a foreign invader.3
Antibodies are be made against these tTG enzymes, creating an autoimmune disease. This simply means that your immune system attacks your own cells and tissues. This process is often in the gut, but it can be found in the brain as well. However, we’ll save this portion for another time as autoimmunity is a discussion all of its own! The important thing to understand here is that CD is an autoimmune disease – a process in which your immune system attacks your own intestinal cells, breaking down your intestines, creating malabsorption, inflammation, and pain.
Celiac Disease and Genetics
People suffering from CD, in some cases, are unable to tolerate even traces of gluten. CD, thought to be genetic in nature, as it’s associated with two major genes called HLA-DQ2 and HLA-DQ8.4 Let me just stop here and say, just because you have these genes, it does not mean that you automatically have Celiac Disease. Instead, it means that you are at a greater risk for developing CD.
Without going into a whole diatribe about how your genes are not your fate, it’s important to understand what that statement really means. Your genes can put you at an advantage or a predisposition, but they need to be “turned on” in order to start replicating. Once they turn on, they are active, BUT nutrition can help increase or decrease the expression of these genes ultimately altering the outcome of whatever these genes express.
For example, I mentioned above that those with CD often have the HLA-DQ2 or -DQ8 gene. Just because someone has this gene does not mean that they will become celiac. However, their risk when consuming gluten increases substantially because gluten can turn this gene on.
Remember the game telephone? The one you played as a child where you’d whisper one thing to the friend next to you, then that friend would whisper it to the friend next to them and so on, and when you finally reach the last person, the message is all kinds of wrong? That’s basically what’s happening with gliadin and CD.
The gliadin protein makes its way into the gut where it’s broken down. But because humans aren’t able to break the protein down completely, it fragments into large chunks – the first telephone message. The gliadin peptide, or message, binds to HLA-DQ, which shows it to the antigen-presenting cell (APC) and says, “I’m not sure what this is – it might be a threat.” So the APC presents the gliadin fragment to the next friend, which is a T cell.
At this point, the message is a little stronger, “the gliadin peptide is definitely a foreign invader that is probably going to do the body harm.” The T cell now turns to its army (cytotoxic immune cells) and says, “Hey, this is floating around in the body and means to start a war. If you see it, capture it, and make sure to tell all your buddies about it too.” The immune cells now only hear one message when it comes to gliadin – “surround and sequester it at all costs.” This means that gliadin has started a firestorm of immunity, creating inflammation, pain, and discomfort.
So why doesn’t this happen to everyone? Why is it only to those with CD? Well, the research is still debated in the literature, but it’s believed it comes back to those specific HLA-DQ genes, of which there are multiple kinds.
The -DQ2 and -DQ8 have a higher binding affinity, meaning they grab on tighter to the gliadin fragment than other versions of HLA-DQ genes. Having a higher binding affinity means that there’s a greater chance that a game of telephone will start – the message is going to reach the next friend in line. Whereas with a lower binding affinity, the message might be lost before the game can begin.
For people possessing the HLA-DQ2 or -DQ8 genes (90-95% and 5-10% of those with CD, respectively), avoiding gluten means less chance of gliadin fragments being bound tightly and starting telephone in the immune system. Once that CD has set in, avoiding gluten quiets the reaction and keeps the immune response down.
Okay, that was A LOT of science. Here’s the rundown: those with Celiac Disease are thought to have increased zonulin receptors, which basically means that eating a lot of gluten will create a leaky gut.
A leaky gut lets gliadin fragments move out of the intestines into the bloodstream, where they are tagged by the immune system. Again, those with CD tend to have a genetic predisposition that allows much tighter binding to the gliadin, ensuring that the immune system marks gliadin as a threat to the body.
This overactive immune response means that normal intestinal cells are destroyed by the immune system, nutrients are not absorbed properly, inflammation, digestive issues like diarrhea, constipation, brain fog, chronic fatigue, and many other symptoms will ensue.
Celiac Disease Signs and Symptoms
CD is often very painful and well, uncomfortable. Quality of life tends to go down for those experiencing CD flare-ups. These people often report having abdominal discomfort, feeling bloated and gassy, and have diarrhea and/or constipation.
Others report fuzzy thinking, decreased memory, an inability to lose or gain weight, anemia, arthritis, and chronic fatigue. However, nearly all who go gluten-free report feeling a relief of symptoms.
What to do if you suspect you have CD
Try going gluten free using an elimination diet to see if going gluten free actually improves your symptoms. If it does, then you can get blood tests to confirm. Cyrex Labs has a series of labs that can be run to determine tTG antibody status, but you’ll have to run those through a physician.
Your physician can also perform an intestinal biopsy as well as run genetic tests to see if you have the HLA-DQ2 or –DQ8 gene. Just be aware that if you only run the genetic test, it is possible to have one or both of those genes and not have CD.
Really, the cheapest and easiest thing to do, is to try going gluten free. If it makes you feel better, then just stay gluten free.
1. Pizzorno J. Zonulin! The wheat conundrum solved (well, mostly …). Altern Ther Health Med. 2014;20 Suppl 1:10-15. https://www.ncbi.nlm.nih.gov/pubmed/24473980.
2. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011;91(1):151-175. doi:10.1152/physrev.00003.2008.
3. Gasbarrini G, Mangiola F. Wheat-related disorders: A broad spectrum of “evolving” diseases. United Eur Gastroenterol J. 2014;2(4):254-262. doi:10.1177/2050640614535929.
4. Tonutti E, Bizzaro N. Diagnosis and classification of celiac disease and gluten sensitivity. Autoimmun Rev. 2014;13(4-5):472-476. doi:10.1016/j.autrev.2014.01.043.