Much of the time when people are talking about gluten, the conversation seems to involve praising or denigrating someone who has declared themselves gluten-free even though they do not have celiac disease. (Perhaps you’ve even seen this video about how to be gluten intolerant?)
Since there seems to be some misunderstanding about what gluten does in the body, let’s see if we can shed light on why it’s not only people with celiac disease who are rightfully concerned with their gluten intake.
(By the way, this is part 2 of the Understanding Gluten series. Part 1 defined what gluten is and where it is found.)
How does gluten impact digestion?
As mentioned in Part 1, gluten is a protein found in certain grains. Normally during digestion, the body breaks down food into its building blocks including monosaccharides, amino acids, fatty acids, vitamins, minerals and phytonutrients. So, one would think that our bodies would separate the gluten from the carbohydrates and then break the gluten into amino acids – either individual ones, or groups of two or three that can be easily absorbed and utilized. Unfortunately, it doesn’t work this way.
Humans appear not to make the enzymes necessary to completely break apart the gluten protein. We have the ability to break gluten into several sections (aka, peptides), but these peptides do not get broken down further.
The first break separates the two main proteins: glutenin and gliadin. Glutenin seems to be digested completely, as we expect proteins to be. However, gliadin is only broken down into peptides of 5 or more amino acids, some of which are called gluten exorphins.
To summarize: humans are incapable of completely digesting gluten into amino acids, di- and tri-peptides. As such, some medium-length peptides remain at the end of gluten digestion.
What happens with glutenin?
Glutenin and its fractions appear to be the primary triggers of IgE antibodies in those with a wheat allergy. The reaction may result in respiratory, skin, or gastrointestinal symptoms. Because IgE allergies are well-recognized by people who suffer from them, I won’t cover them in depth here. (Note: a person with a wheat allergy may be triggered by one or more of the peptides in gliadin, although this is less common than reactions to glutenin.)
What happens to gliadin in the small intestine?
Research so far suggests that gliadin causes problems as a whole and as peptide sections.
As gliadin passes through the small intestine, it triggers the intestinal cells to release zonulin, a protein that opens the tight junctions between the intestinal cells. Although the amount of zonulin released varies from person to person, everyone appears to release at least some upon ingestion of gluten, which means that everyone experiences some relaxation of the intestinal tight junctions. (Check out my video about leaky gut to understand why this is a problem.)
Interestingly, people who are susceptible to autoimmune disease (any autoimmune disease, not just celiac disease) tend to release more zonulin when triggered than those who are not genetically susceptible.
In very healthy people who are not over exposed to gluten, the tight junctions close quickly and gut function returns to normal. However, for people who consume a lot of gluten (like cereal for breakfast, a sandwich for lunch, and pasta for dinner) and those who are susceptible to autoimmune disease, zonulin is released in large amounts and the tight junctions stay open for an extended period of time (i.e., leaky gut).
Gliadin also effects the function of the intestinal cells. These changes include:
- Alterations in communication between the intestine and the immune system,
- Increased apoptosis (i.e., cell suicide), and
- Changes in the cell’s “skeleton” which ultimately leaves the cell deformed.
In people with a genetic susceptibility to celiac disease, this last change is likely the one that triggers the adaptive immune system to create anti-tTG and EMA antibodies to clean up the damaged epithelial cells.
To summarize: gliadin impacts the integrity of the small intestine by 1) causing the tight junctions to open, 2) changing how the intestine communicates with the immune system, 3) increasing intestinal cell death, and 4) damaging the epithelial cell structure.
Of course, the impact doesn’t stop there. Because gliadin opens the tight junctions, gliadin and other peptides “leak” into the blood stream. (Again check out my video about leaky gut if this is confusing.)
What happens when the gliadin or glutenin peptides enter the blood stream?
While there may be lots of reactions that we aren’t aware of yet, research has shown the following…
- Exorphins may be absorbed into the epithelial cells and then into the blood stream or pass directly into the blood stream through compromised tight junctions. Once in the blood stream they may:
- Cross the blood-brain barrier which can trigger a number of cognitive conditions including depression, anxiety, migraines, epilepsy, dementia, ataxia, Huntington’s disease, autism and schizophrenia
- Trigger the pancreas to release more insulin and the pituitary gland to release more growth hormone (although this has only been shown in animal studies so far)
- Gliadin-derived peptides may…
- Trigger a response from the innate immune system which damages the small intestine cells and leads to quicker turnover. Ultimately, this means the intestine wall may not fully develop. Note: this may be the link between gluten / IBS and gluten / GERD, although it’s not totally clear based on research to date.
- Trigger the adaptive immune system to create deamidated gliadin antibodies (DGA), which are also a hallmark of celiac disease.
- Trigger the adaptive immune system to create antibodies against any number of fractions of the gliadin peptide. To date, research has confirmed the body can create antibodies to 33-mer, alpha-gliadin-17-mer, gamma-gliadin-15-mer and omega-gliadin-17-mer.
- Gliadin itself may trigger the adaptive immune system to create anti-gliadin antibodies of IgG or IgA class (i.e., not the deamidated version of gliadin). People with celiac disease tend to have sustained high levels of anti-gliadin IgG (regardless of diet) and increased levels of anti-gliadin IgA with gluten consumption. People with gluten sensitivity show very little anti-gliadin IgA activity (regardless of diet), but increased levels of anti-gliadin IgG with gluten consumption. It is worth noting that not everyone with IgG antibodies will have an immune reaction leading to symptoms when gluten is consumed.
- As well, there is evidence that the body may create IgG or IgA antibodies against the 21-mer fraction of the glutenin protein.
It is worth noting that the body may be creating antibodies against other fractions of the gluten protein and we simply haven’t discovered them yet.
To summarize: gluten’s peptides can trigger the immune system in multiple ways, impact cognitive function, and trigger excess hormone release by certain endocrine organs. The extent of the resulting damage depends on how much gets into the epithelial cells and blood stream and on your genetic susceptibility, physiology and environment.
In part 3 of this series, I cover the ways these reactions may manifest in the body. I think you will be surprised by some of them (like gallbladder problems)!
And in part 4, I talk about the prevalence of gluten sensitivity and the theories about why it is on the rise. Also, I give my recommendation about who should avoid gluten.
1) It has been recommended that traditional grain cooking methods that require fermentation, as would be done with sourdough bread for example, break down gluten. Research seems to support that certain Lactobacillus bacteria have the enzymes necessary to digest the proline-rich peptides. An alternative proposal is that the long period of time in which the grains are soaking in an acidic solution breaks apart the gluten protein, and specifically the peptides in question. In either case, the gluten peptides are not in tact at the time of ingestion and therefore do not need to be digested by us.
2) Just for completeness, gliadin is not the only trigger for zonulin release. Exposure of the intestine to bacteria can trigger zonulin release, which is believed to be one of the reasons why dysbiosis causes leaky gut. As well, casein (a dairy protein) ingestion in some individuals. (I’ll talk about all of the potential causes of leaky gut in my second video, so stay tuned!)
3) Many people who are genetically susceptible to celiac disease maintain their anti-gluten antibodies of IgG class, even when on a gluten-free diet. This may be one of the reasons that people with celiac disease are impacted by every exposure to gluten, while people with gluten sensitivity may not be after following a gluten-free diet for an extended period of time.
4) It is important to note that all of the conditions mentioned above are complex with multiple potential causes (of which gluten is only one) and, therefore, multiple solutions. That is why I used the word “may” throughout. If you or a loved one is suffering from one of these conditions, please consult with a qualified healthcare practitioner (like me) to determine the best course of action for you.
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