Why Do People Go Gluten Free?
You can see gluten-free food almost everywhere. What’s the big deal? Well, around 1% of the world population can’t eat gluten or else they will experience stomach pains, diarrhea, or even malnutrition. This is because these people suffer from a condition called celiac disease.
Gluten and Celiac Disease
Celiac disease symptoms were first recorded 2000 years ago by the Greek physician Aretaeus, who observed his patients suffering from diarrhea and malnutrition. He named the disease “koiliakos” (κοιλιακός), meaning “abdominal” in Greek, which later became “coeliac disease” when his work was translated. The cause of celiac disease was much later discovered by Dr. Willem Karel Dicke during the Dutch famine of World War 2. During this time, delivery of bread to hospitals was halted, but Dr. Dicke observed that his patients with celiac disease paradoxically improved. When supplies began being delivered again after the war, his patients deteriorated. Dr. Dicke realized that wheat intake, specifically gluten intake, was the main cause of celiac disease.
So what is Gluten?
Gluten is a group of proteins found in wheat, barley, and rye. For example, in wheat, the gluten proteins are gliadin and glutenin. Derived from the Latin word for “glue”, gluten is responsible for making dough elastic and sometimes used as a thickener. So, it’s not surprising that it is found in most baked goods, pasta, cereals, beer, and even some processed foods like French fries and canned soups.
What happens when someone with celiac disease eats Gluten?
The small intestine is where our body absorbs the nutrients and water from the food we eat. In people with celiac disease, gluten initiates an autoimmune reaction that damages the intestinal wall. Intraepithelial lymphocyte numbers skyrocket and kill the epithelial cells, resulting in shorter and flatter villi, while crypts deepen as the intestine tries to replenish the dead epithelial cells. Now there is reduced surface area, meaning less nutrient absorption. Less water and fat absorption in the small intestine leads to symptoms such as diarrhea and steatorrhea, while less nutrient absorption may result in weight loss, fatigue, anemia, osteoporosis, or even increased bleeding risk. Furthermore, bacteria that live in the small intestine can use up the unabsorbed nutrients, releasing gas that causes bloating.
How does Gluten trigger intestinal damage?
In short: eating gluten-containing food starts a positive feedback loop where damage makes it easier for more gluten to enter, worsening the situation and resulting in the symptoms mentioned earlier. While most proteins are broken down into individual amino acids or small peptides in the small intestine, our digestive enzymes simply cannot break down gluten proteins very efficiently because gluten proteins contain high amounts of two amino acids: proline and glutamine.
This results in large gluten peptides that cross the epithelial cells and enter the lamina propria in a few different ways. Overexpression of the zonulin gene creates wider gaps between cells for gluten peptides to enter. Gluten peptides can also be transported across cells by binding to receptors. Finally, there seems to be evidence that certain gluten peptides can directly damage epithelial cells, creating openings for more gluten peptides to flow through. Once inside the lamina propria, these peptides are then modified by an enzyme called tissue transglutaminase, which is normally found within cells but released and active during tissue damage. This enzyme changes the glutamine residues to glutamate, resulting in a more negatively charged peptide fragment. Remember this step – it will be important later. Now, the immune system gets involved. The intestinal tissue is constantly patrolled by dendritic cells, which play a huge role in alerting the immune system if they find anything harmful. The way they do this is by presenting peptides they have found in the environment on their surface by using special display proteins called MHC class II proteins.
For example, during a bacterial infection, many bacteria are in the environment, and so the peptides displayed on the surface of dendritic cells would likely be from a bacterial protein. Helper T cells, the main regulators of the adaptive immune system, will then “check” if their unique T cell receptor can bind to the peptide. If it can, that helper T cell is activated, proliferates, and starts the immune response. T cell receptors are designed so that they won’t bind to any peptides normally found in our body, so helper T cells are only activated when they find something that doesn’t belong in our body. In the case of gluten, modified gluten peptides are found and displayed by dendritic cells on their MHC class II proteins. Since gluten peptides aren’t found in our body, the appropriate helper T cell is activated.
These helper T cells have three functions. First, they release inflammatory molecules to cause stress to the epithelial cells. Helper T cells also release molecules that cause activation and proliferation of intraepithelial lymphocytes, which recognize and kill these stressed epithelial cells, causing more gluten peptides flow in to exacerbate the situation. Finally, helper T cells activate B cells which make antibodies against these gluten peptides, as well as against tissue transglutaminase. Though the extent of damage caused by these autoantibodies is not well understood, they play a key role in diagnosis.
So why do some people have an immune response to gluten, while most people do not?
This can be explained by the variations in MHC class II molecules. There are three main types of MHC class II molecules: HLA-DP, DQ, and DR. These three types also have many different isoforms, each of which have a different binding pocket, allowing it to bind to different peptides. Each person has 2 isoforms of each type, inherited from each parent, making each person’s combination of MHC class II molecules, as well as the range of peptides their dendritic cells can present, slightly different from another person. The only isoforms that can bind to gluten peptides are HLA-DQ2 and HLA-DQ8, which bind extremely well to negatively charged peptides such as the gluten peptides modified by tissue transglutaminase as mentioned earlier. Without HLA-DQ2 or 8, dendritic cells cannot present gluten peptides to activate T cells. So it makes sense that virtually all people with celiac disease have either HLA-DQ2 or 8.
How to diagnose Celiac disease?
Celiac disease can show up as any combination of these symptoms, making it very difficult for doctors to diagnose, or even consider, celiac disease to be the cause of their patient’s discomfort. This is why scientists estimate that around 80% of people with celiac disease have not been correctly diagnosed. This is a serious problem because if left untreated, celiac disease can lead to neurological damage, infertility, or even cancer. Please talk to your physician to get tested if you are experiencing celiac disease symptoms, or if your family members have celiac disease.
Testing for Celiac Disease
Testing for celiac diseae requires you to eat gluten-containing foods for 6-8 weeks for the antibodies to build up and damage to be detected. This should only be done under the supervision of a dietician or trained physician. You can also get genetic testing to see if you have HLA-DQ2 or 8. If you don’t have these isoforms, great! Because it’s virtually impossible for you to develop celiac disease. If you do have them though, it doesn’t necessarily mean you will develop celiac disease, but it does put you at an increased risk and more tests should be performed throughout your life. This is mostly done by the relatives of people with celiac disease to rule out the possibility of developing celiac disease themselves. Since eating gluten is the reason why the intestines get damaged, the only effective treatment available is going on a gluten-free diet.