Gluten Intolerance Is Not Real – Or Is It?

Written By: Jakub Kalus

Gluten has become a hot topic in last few years. The phenomenon of gluten intolerance is increasingly more common. More and more people are following a gluten-free diet, and claiming that this step helps them feel less bloated, dizzy, and constipated. In tandem, we’ve seen a rise in the number of gluten-free products and diets.

Unfortunately, no evidence suggests that gluten intolerance is a “real thing“ – after ingesting gluten, there are no markers of immune response. This is especially surprising in comparison with celiac disease, where the response of the immune system is significant.

Recently, however, there has been some interesting new research about the gluten intolerance phenomenon.

In order to understand the controversy, we must first dive deep into the characteristics of gluten. Gluten is a composite of proteins which can be found in wheat, rye, barley, spelt, and also in small amounts in oats.1 We can find it pretty everywhere in our kitchen – from pastry to pasta, cereals or beer, you name it. Gluten makes the dough sticky: that’s why wheat bread is more palatable and chewy than gluten-free corn bread.

Celiac Disease

A small proportion of people (roughly less than 1%) may be genetically predisposed to celiac disease – and it may develop in any age.2 Celiac disease (CD) is a condition that is very closely associated with the presence of specific human leukocyte antigens: HLA-DQ2 and HLA-DQ83. Those with this disease experience an immune response after ingestion of gluten, which leads to inflammation in the small intestine and other symptoms such as severe abdominal pain, diarrhea, malabsorption, joint pain, skin rash, and even fatigue and cognitive difficulties. In several cases, however, the symptoms are not so severe4, so there still are many people with undiagnosed CD. In reality, roughly 0.2-0.3% of those with this disease know that they have it, and 1% of the population at large has CD. But I’d bet that more than 1% of the people who you know try to avoid gluten, right?

For those with clinical CD, damage to the small intestine occurs after consumption of any food containing gluten. This leads to atrophy of intestinal villi, which are important structures that increase the surface area of the intestinal wall, and thus our rate of absorption. But if atrophy occurs, the surface area decreases and our absorption rate is hindered. The damage also occurs as hyperplasia of intestinal crypts, which are responsible for absorption of the nutrients. So the consumption of gluten leads not only to digestive issues, but also to malabsorption or malnutrition – and this condition can lead to anemia, osteoporosis, or even infertility.

On top of that, any additional contact with foods containing gluten (and particularly gliadin, one of the proteins which forms gluten) makes the situation worse and also damages the villi. This means that the absorption of nutrients from even gluten-free foods also deteriorates until the villi heal themselves. The only “cure“ for true celiac disease is a life-long adherence to gluten-free diet.

Gluten Intolerance: What’s the Difference?

In past years, people have noticed that they don’t feel well after consuming any food containing gluten, so they consider themselves as gluten-intolerant. Unfortunately, gluten intolerance is not a medical term, nor does it have any specific genetic, serological, or histological markers. There are no physical examination methods to identify this condition, so these people often get told that they have irritable bowel syndrome, which is sometimes linked with mental problems, or non-celiac gluten sensitivity.5,6

In comparison, when it comes to celiac disease, both the influence of genetics and the markers of this condition are known. For example, IgG and IgA antibody reactivity to deaminated gliadin or autoantibodies to transglutaminase 2 – that’s an enzyme which modifies the gluten peptides, and this modification leads to increased binding affinity to human leukocyte antigen and launches a strong immune response.7,8

Further Exploration

So the gluten-sensitive people tried to eliminate gluten from their diets and felt better – that’s awesome! But why exactly did they suddenly feel better, and why did gluten cause them gastrointestinal issues when it shouldn’t have?

Interesting research about a specific group of carbohydrates called FODMAPs may offer a clue. FODMAP stands for fermentable oligo- di- mono- and polyols, which are present not only in pastries but also in beans, chewing gum, and other types of foods, and which can cause bloating in some people. The research suggested that gluten itself is not the culprit causing gastrointestinal discomfort, but the FODMAPs, which are often present concurrently with gluten. In addition, a diet low in FODMAPS decreased the symptoms of irritable bowel syndrome.9

So it seemed that those people who thought they have a gluten sensitivity have missed the bigger picture. They were just more sensitive to the foods high in this group of carbohydrates, which happens to also include foods containing gluten. But this experiment didn’t explain why some people could resume eating foods containing gluten after eliminating it from their diets for a period of time, and found no negative effects.

The most important recent study on this topic, conducted by scientists from Columbia University, discussed the difference in reaction of our body of individuals with celiac disease and those with self-reported gluten intolerance.10 In those with celiac disease, the inflammatory process is present only in the gut, and the immune system suppresses any microbial products that can enter the blood and cause systematic immune response.

On the other hand, scientists have found a rise in specific markers in people with gluten sensitivity. These markers – including biomolecules such as sCD14 and lipopolysaccharide-binding protein, as well as antibody reactivity to microbial agents – were not previously linked to gluten intolerance or celiac disease. What does it mean for those of us who are not doctors or scientists? In the case of gluten intolerance, our bodies react by systemic immune activation, not only a local response, as was the case in people with celiac disease who did not mirror these changes.

Individuals with gluten intolerance also had elevated levels of fatty acid-binding protein 2, which is a marker of intestinal epithelial cell damage.11 That suggests that the integrity of the intestinal barrier is compromised in people with gluten sensitivity.

The Bottom Line?

All of this indicates that the barrier of the intestine in these individuals is damaged, which can lead to translocation of microbial products into blood vessels. You can imagine the same principles as if there were holes in a barrier, allowing unwanted substances pass through. This leads to a systemic immune response of our body to pathogens which cross the intestinal barrier.12 After elimination of wheat for a period of time, the barrier should heal itself and should no longer be permeable to potential pathogens. A literature review by Branchley and Douek offers supporting evidence: many of the included studies showed lower concentrations of relevant biomarkers after six months of gluten avoidance.

While gluten intolerance might not be the same as clinically diagnosed CD, the studies cited above suggest that it is still a “real thing”, and not just some made-up condition which cannot be measured.

If you aren’t a celiac but you don’t feel well after ingesting foods which contain gluten, just try to eliminate these foods from your diet for a short period of time –  for a  few months or so. Let your intestinal barrier heal, and then try to reincorporate these foods to your diet. Hopefully, you should feel improvement in your tolerance to foods that include gluten or, if you are lucky enough, you will be able to enjoy as many pizzas and beers as you want, without restriction, for the rest of your life.


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2) Sollid  LMMcAdam  SNMolberg  O  et al.  Genes and environment in celiac disease.  Acta Odontol Scand. 2001;59183- 186

3) Cecilio LA, Bonatto MW. The prevalence of HLA DQ2 and DQ8 in patients with celiac disease, in family and in general population. Arq Bras Cir Dig. 2015;28(3):183-5.

4) Fasano A (Apr 2005). “Clinical presentation of celiac disease in the pediatric population“. Gastroenterology (Review). 128 (4 Suppl 1): S68-73

5) Carroccio, A., Mansueto, P., Iacono, G., Soresi, M., D’alcamo, A., Cavataio, F., Pirrone, G. (2012). Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. The American journal of gastroenterology, 107(12), 1898-1906.

6) Catassi C, Bai JC, Bonaz B, et al. Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders. Nutrients. 2013;5(10):3839-53.

7) Sollid LM, Jabri B. Celiac disease and transglutaminase 2: a model for posttranslational modification of antigens and HLA association in the pathogenesis of autoimmune disorders. Curr Opin Immunol. 2011;23(6):732-8.

8) Rauhavirta T, Hietikko M, Salmi T, Lindfors K. Transglutaminase 2 and Transglutaminase 2 Autoantibodies in Celiac Disease: a Review. Clin Rev Allergy Immunol. 2016;

9) Halmos, E. P., Power, V. A., Shepherd, S. J., Gibson, P. R., & Muir, J. G. (2014). A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology, 146(1), 67-75.

10) Uhde M, Ajamian M, Caio G, et al. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016;

11) Pelsers, M. M., Hermens, W. T., & Glatz, J. F. (2005). Fatty acid-binding proteins as plasma markers of tissue injury. Clinica Chimica Acta, 352(1), 15-35.

12) Brenchley JM, Douek DC. Microbial translocation across the GI tract. Annu Rev Immunol. 2012;30:149-73.


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