The Complex Etiology of Celiac Disease Includes Gluten, Pathogens, Predisposed Host Microflora and Immune Response

Student guest post by Ahn To

There are two separate philosophies regarding the relationship between life and food. There are those that believe we only eat to live. On the other hand, there are those that believe one of life's greatest pleasures is food. I am a firm believer of the latter, thus, you can imagine my horror when I first learned of celiac disease (CD). This is a disease with no treatment except for a lifetime on a gluten-free diet, thus people with CD cannot eat many types of food. I knew then that I had to find out more about causation of CD, which includes the complex interaction between genes, "gluten", immune response, microflora and infections.

CD has both genetic and environmental contributing factors. Genetic factors, being homozygous or heterozygous for HLA-DQ2 or HLA-DQ8 genes, which are coded for class II antigen presenting cells in the immune system, confer susceptibility to CD. However, these genes are much more common than the number of people with CD, thus there may be other genetic contributions. Future studies are needed to identify them. Environmental factors, proline- and glutamine-rich proteins (widely known as gluten) are believed to be the trigger of the diseases. There is also evidence that infections may have a role in CD etiology.

CD is an autoimmune disease. In an infection, the immune cells target non-self antigens on the pathogens. Once the pathogens are eradicated, the immune system becomes deactivated. As the immune system fights the pathogen, it may damage some tissue, but that is not a problem since the body has an innate capacity to heal itself. In an autoimmune reaction, the antigens that the immune system target cannot be completely eradicated because they are self antigens, and so the fight doesn't end. As time passes, the body's capacity to heal cannot keep up, which results in severe damage to the body. The underlying causation of an autoimmune disease is the immune system's failure to differentiate between self and non-self antigens.

There are several hypotheses regarding infection roles in CD. One of which is "molecular mimicry". This theory proposes that there are antigens on pathogens that are similar enough to host antigens that after the immune system cleared the pathogens' antigens, it mistakes the host antigens as pathogenic and starts to attack the host antigens. Another theory proposes that infections alter intestinal permeability, which allows "gluten" peptides to encounter HLA-QB, which lead to tissue damages through an influx of "gluten"-specific T cells. In CD, the immune system causes villous atrophy and crypt cell hypertrophy, which result in malabsorption of nutrients.

An association between being born in the summer and having an increased risk for CD was discovered in 2003 through analyzing data from a population based registry of celiac disease in Sweden. The reason for this was speculated to be a higher rate of infection and easier food spoilage in the summer. Thus a child born in the summer has a higher risk of getting an infection that can contribute to CD pathogenesis. Along the same line of reasoning, there was a review in 2009 that indicated that perinatal infections and maternal-milk may have a protective role in CD development. That same review also linked CD to Adenovirus 12 or Hepatitis C virus. Rotavirus infection was also linked to CD in a prospective cohort study of 1,931 children in the Denver metropolitan areas. That study also found that repeated infections of Rotavirus correlate to a higher risk than single infection. However, not all infections increase the risk of having CD. In a retrospective serological case-control study, Leeor Plot et al. found that having past infection of Rubella, CMV or EBV actually has a protective effect leading to a decrease in the risk of having CD. This indicates that pathogenic infections are only a part of the story.

A case-control by Tjellstrom et al. indicates that there is a difference in the metabolic activity of intestinal microbial flora in CD patients. Thus, it is reasonable to propose that it is an interaction between microflora, infectious agents, gluten and the immune system in a genetically predisposed person that causes CD.

Having CD doesn't mean you have to stop enjoying food. As I talked to people with CD, who are on a gluten free diet, they referred me to many websites dedicated to gluten-free cooking. These websites not only have gluten free recipes for daily meals, but also yummy desserts like cookies and cakes. If you are looking for a wheat substitute, you should check out rice. There are around 40,000 different kinds of rice to choose from. Moreover, since Asian food has a strong emphasis on rice instead of wheat, you can find many delicious ethnic dishes that are gluten-free: rice and chicken curry from India, pho from Vietnam, papaya salad from Thailand... Of course, you can still eat out, since many restaurants have a list of which dishes are gluten-free or you can specifically request gluten-free dishes. So it is possible to enjoy good food when one has CD. However, I hope that future research can modify the interaction between gluten, pathogens, host microflora and immune response in genetically predisposed individuals to prevent the onset of CD, so people can eat whatever they want.


1.Ivarsson A, Hernell O, Stenlund H, Persson LA. Breast-feeding protects against celiac disease. Am J Clin Nutr 2002;75:914-921.
2.Kagnoff MF. Celiac disease: pathogenesis of a model immunogenetic disease. J Clin Invest. 2007;117:41-49.
3.Plot L, Amital H. Infectious associations of Celiac disease. Autoimmun Rev. 2009;8:316-319.
4.Plot L, Amital H, et al. Infections May Have a Protective Role in the Etiopathogenesis of Celiac Disease. Contemporary Challenges in Autoimmunity 2009: Ann. N.Y. Acad. SCi. 1173:670-374.
5.Stene, LC, Honeyman, MC, Hoffenberg, EJ, et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: A longitudinal study. Am J Gastroenterol 2006;101:2333-2340.
6.Tjellstrom, B., Stenhammar, L., Hogberg, L., Falth-Magnusson, K., Magnusson, K. E., Midtvedt, T., Sundqvist, T. & Norin, E. (2005). Gut microflora associated characteristics in children with coeliac disease. Am J Gastroenterol 100, 2784-2788.

More like this

As someone who has a parent with CD (meaning I am at risk), I can appreciate that people are researching it!

I think I'll pass on getting Rubella, however.

My parents tell me that celiac disease (CD) is primarily a childhood disease, but it seems that there are now more people acquiring the problem in older age - but that's anecdotal, and may be wrong.

The main problem with a gluten-free (GF) diet is simply inconvenience. Typically GF diets have to be free of gluten because it's an immune system reaction, not just low on gluten (so it differs from many lactose-intolerance diets, where a small exposure to lactose is not a big thing for many sufferers). When cooking proper meals at home, going GF is not difficult: simply avoid pastry, bread and wheat flour, fill the cupboard with GF versions of things like soy sauce, stock cubes, etc., use corn or potato flour for thickening (where it's the starch in flour that is needed).

So GF food is exactly as good as non-GF food, unless the gluten is actually needed for its stringy strength, as when it is used to hold together the aerated structure of risen bread.

But go out to eat, especially in a group, and food that could easily be GF will often not be: soups, sauces, etc. So menus have to be scrutinised with care and questions asked.

And, of course, nice bread and any sorts of cakes and pies disappear from the diet, as does the option for making a simple sandwich. GF bread varies, but none of it is a patch on wheat bread.

Thank you for the interesting post, it's a very handy guide.

I had heard that there were reasonably reliable genetic tests now for susceptibility, but maybe I'm out of date (I don't have CD, I just have to cook GF for CD people sometimes, so this is all third-hand).