gluten and autoimmune diseasePublished in Nutritional Perspectives Journal January 2015
By. Dr. Michael Jurgelewicz

Celiac disease is an autoimmune disease triggered by the consumption of gluten-containing foods. The medical approach for celiac disease is a lifelong gluten-free diet. However, recent evidence demonstrates that a gluten-free diet may not be enough to prevent many complications associated with this disease.

Many patients with celiac disease have a significant improvement removing gluten from their diet. However, seven to thirty percent of people continue to have symptoms of celiac disease despite a gluten-free diet.1 Few studies have looked at the effect of non-gluten proteins and celiac disease. An all-too-common contributor to non-responsive celiac disease is cross-reactivity with other foods. Antibody cross-reactivity between different foods or between food and aeroallergens, such as trees and grasses, occurs much more readily than clinically evident cross-reactivity.2 In addition, a recent study published in J. Proteome Research demonstrated that celiac disease patients had significantly higher levels of antibody reactivity to non-gluten proteins than healthy controls. The main immunoreactive non-gluten antibody target proteins were identified as serpins, purinins, α-amylase/protease inhibitors, globulins and farinins.3

There has also been controversy whether oats should be avoided for people with celiac disease because they contain proteins called avenins, which are similar to gluten. Researchers conducted a 10-year study just published in the Journal of Autoimmunity. They revealed that oat consumption triggered an immune response in eight percent of the 73 participants with celiac disease.4
Assessing gluten-associated cross-reactive foods is essential for patients with gluten sensitivity and celiac disease since these patients are sensitized to a broad range of dietary proteins due to enzyme dysfunction, villi damage and other disorders.

According to The Celiac Disease Foundation, an estimated 2.5 million Americans have celiac disease and do not know it. The current testing for celiac disease and gluten sensitivity include serum IgG and IgA against gliadin and tissue transglutaminase-2. These proteins are measured against minor components of a wheat protein called alpha-gliadin. Wheat, however, consists of multiple proteins and peptides including, alpha-gliadin, omega-gliadin, glutenin, gluteomorphin, prodynorphin and agglutinins. Any of these antigens can elicit an immune response and these are rarely tested, so there are many false negatives. Many patients with celiac disease do not have the traditional gastrointestinal symptoms and may only present with nutritional deficiencies and anemia.5 As a result, people with celiac disease usually get misdiagnosed for quite some time due to an atypical presentation and therefore more villous destruction has occurred. Unfortunately, by the time villous atrophy occurs, the individual is very sick with many symptoms. Consequently, many functional abnormalities can persist such as increased gut permeability, pancreatic insufficiency, small-intestinal bowel overgrowth, lactose intolerance and milk allergies.6 Due to increased inflammation, the digestive and absorptive processes become compromised in celiac patients.

Patients with celiac disease have nutritional deficiencies and altered lipid profiles, such as a low HDL concentration.7,8 In addition, celiac disease patients are more vulnerable to pancreatic insufficiencies, dysbiosis, vitamin D deficiencies and osteopenia.1

Celiac patients can have compromised gallbladder function and motility.9 A gluten-free diet does improve gallbladder dysfunction; however, this is something that should be assessed to further improve gallbladder function and fat-soluble vitamin absorption.

There is also a significant amount of research on the changes in intestinal flora and autoimmune disease. Complete normalization of gastrointestinal lesions is very rare in adult patients with celiac disease (8%), despite gluten-free diet compliance. Although a majority (65%) feels better, the inflammation in the gastrointestinal tract due to cross-reactions to food antigens remains a cause for clinical concern.10 Furthermore, an acute gluten-free exposure can increase intestinal permeability with marked luminal zonulin release by seventy percent.11 Although most patients do a great job avoiding gluten, it can sometimes be difficult with cross contamination of food, beverages and utensils.
When we look at the gut microbiota as seen in several functional laboratories, a gluten-free diet does not appear to normalize the reduced ratio of Lactobacillus-Bifidobacterium to Bacteroides-E.coli. In addition, the decreased fecal elastase-1 identifies a persistence of pancreatic insufficiency.12,13 Therefore, these patients would benefit from digestive enzymes to support optimal digestion.

Regardless of adhering to a lifelong gluten-free diet, celiac patients continue to have poor nutrient status. Celiac disease attacks and damages the villi of the small intestine, resulting in the body not being able to absorb all the nutrients it needs. The most common deficiencies are vitamin D, calcium, folate, vitamin B12 and iron. In untreated celiac disease patients, small intestinal villous atrophy can contribute to a vitamin D deficiency.14 In addition, many patients that suffer from gastrointestinal symptoms are on proton pump inhibitors, which play a role in calcium absorption. Milk intolerances and allergies also reduce sources of calcium.

Untreated celiac disease may be associated with hyperhomocysteinemia caused by a combination of vitamin deficiencies and variants in the MTHFR gene.15 Celiac patients may also have a permanent folic acid deficiency from alterations in pH of the small intestine. Therefore, L-MTHF is a better source of supplementation since it is well absorbed over a broad pH range.16

A vitamin B12 deficiency is very common in celiac disease patients. This could be due to an impaired gastric acid status as well as being on proton pump inhibitors. Pancreatic insufficiency can also contribute to lower vitamin B12 levels. Proteases are necessary to separate B12 from salivary R-protein in the upper intestine tract and allow the binding with stomach intrinsic factor.1

Iron deficiency is one of the most common deficiencies of celiac disease. Compromised gastric acid status also decreases iron absorption that requires low pH range. A large amount of gluten-free products contain phytic acid, the storage form of phosphorus that reduces the bioavailability of certain nutrients, such as iron, calcium, manganese and zinc.17

Patients with celiac disease may have to do more than just follow a gluten-free diet to maintain optimal health. Although a majority of celiac patients feel better after implementing a gluten-free diet, the inflammation in the gastrointestinal due to a multitude of food antigens remains a cause for clinical concern. Environmental triggers are what integrative doctors assess in functional medicine. These can be food triggers such as gluten or food sensitivities that can bring about inflammation as well as anything coming in with the food such as toxins or molds. In addition, integrative doctors look at the nutrient status of the person. This can be antioxidant status, vitamins, essential fatty acids, vitamin D, etc. They also evaluate gut health, including “leaky gut” and dysbiosis. Finally, there are toxins that can affect the status of the immune system, such as heavy metals and xenobiotics, as well as the total toxic burden in the body.

What appears to happen with most autoimmune diseases is that there are multiple triggers chronically stimulating the immune system over a long period of time in multiple ways. As a result, the immune system gets into an overloaded, overwhelmed state and loses its ability to function. Lifestyle choices and environmental exposures filtered through genetic predisposition are fundamental factors in the expression of disease, and a successful treatment approach must address these factors. It is important to work with a health care provider that can assess nutrient status and gastrointestinal function in order to co-manage these patients.

1. Green P and Cellier C. Celiac Disease. N Engl J Med, 2007; 357:1731-1743.
2. Eckman J, Saini SS, Hamilton RG. Diagnostic evaluation of food-related allergic diseases. Allergy Asthma ClinImmunol, 2009; 5(1):2.
3. Huebener S et al. Specific Non-Gluten Proteins of Wheat are Novel Target Antigens in Celiac Disease Humoral Response, J. Proteome Res, 20 October 2014.
4. Melinda Y. Hardy, Jason A. Tye-Din, Jessica A. Stewart, Frederike Schmitz, Nadine L. Dudek, Iresha Hanchapola, Anthony W. Purcell, Robert P. Anderson. Ingestion of oats and barley in patients with celiac disease mobilizes cross-reactive T cells activated by avenin peptides and immuno-dominant hordein peptides. Journal of Autoimmunity, 2014.
5. Di Sabatino A, Corazza GR: Coeliac disease. Lancet 2009;373: 1480–1493.
6. Liebert, M. Functional and Metbolic Disorders in Celiac Disease: New Implications for Nutritional Treatment. J Med Food 17 (11) 2014, 1-6.
7. Capristo E, Malandrino N, Farnetti S, et al. Increased serum high-density lipoprotein-cholesterol concentration in celiac disease after gluten-free diet treatment correlates with body fat stores. J Clin Gastroenterol 2009;43:946–949.
8. Capristo E, Addolorato G, Mingrone G, et al.: Changes in body composition, substrate oxidation, and resting metabolic rate in adult celiac disease patients after a 1-y gluten-free diet treatment. Am J Clin Nutr 2000;72:76–81.
9. Fraquelli M, Pagliarulo M, Colucci A, Paggi S, Conte D: Gallbladder motility in obesity, diabetes mellitus and coeliac disease. Dig Liver Dis 2003;35 Suppl 3: S12–S16.
10. A. Lansini, F. Lanzarotto, et al. Complete recovery of intestinal mucosa occurs very rarely in adult coeliac patients despite adherence to gluten-free diet. Alimentary Pharmacology & Therapeutics Volume 29, Issue 12, pages 1299–1308, June 2009.
11. Miele L, Valenza V, La Torre G, et al.: Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology 2009;49:1877–1887.
12. Collado MC, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y: Specific duodenal and faecal bacterial groups associated with paediatric coeliac disease. J Clin Pathol 2009;62:264–269.
13. Medina M, De Palma G, Ribes-Koninckx C, Calabuig M, Sanz Y: Bifidobacterium strains suppress in vitro the pro-inflammatory milieu triggered by the large intestinal microbiota of coeliac patients. J Inflamm (Lond) 2008;5:19.
14. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–281.
15. Wilcox, GM, Mattia, AR. Celiac sprue, hyperhomocysteinemia, and MTHFR gene variants. J Clin Gastroenterol 2006 Aug; 40(7):596-601.
16. Ponziani FR, Cazzato IA, Danese S, et al. Folate in gastrointestinal health and disease. Eur Rev Med Pharmacol Sci 2012; 16:376–385.
17. Gibson RS, Bailey KB, Gibbs M, Ferguson EL. A review of phytate, iron, zinc, and calcium concentrations in plant-based complementary foods used in low-income countries and implications for bioavailability. Food Nutr Bull 2010;31(2 Suppl): S134–S146.

Sharing is caring!