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Leaky Gut Found To Be A Major Contributory Factor To Celiac

Celiac disease, according to estimates, affects approximately three million Americans and as of yet, 97% haven’t been correctly diagnosed. As staggering as these statistics are, celiac disease remains largely poorly understood by the medical community. It’s no wonder, given its lack of research as compared with other autoimmune disorders. However, there is research being actively conducted in the U.S. and internationally in a quest to understand the pathogenesis, or the cause and development of the disease. With this information, more about celiac disease, diagnosis, prevention, and treatment can come to light.

According to the Canadian Celiac Association (CCA), the pathogenesis of celiac disease consists of three factors: “genetic, environment and immunologic.” With regard to genetics, the CCA points out that more than 97% of celiac patients have the genetic markers HLA DQ2 and/or HLA DQ8. Celiac disease is now known to be a hereditary disease. The Canadian Celiac Association tells us that “first-degree and to a lesser extent second-degree relatives are at higher risk of having unrecognized celiac disease.”

Next, is the environmental “trigger,” as Dr. Alessio Fasano, professor of pediatrics, medicine and physiology at the Center for Celiac Research at the University of Maryland School of Medicine, calls it. This is gluten, a protein found in wheat, barley, and rye. According to the Canadian Celiac Association, sometimes severe physical stressors can also trigger the immunologic reaction to gluten that is characteristic to celiac disease. Such sources of stress include pregnancy, infection, surgery, or even severe emotional stress.

In his article, “Surprises from Celiac Disease,” published in Scientific American, Dr. Fasano describes a different triad of factors involved in the pathogenesis of the disease. The first two factors are the ‘’trigger” of gluten, which sets off the immune response, and the genetic predisposition, as previously described. Fasano proposes that “other genes are likely to be involved as well, but these additional culprits may differ from person to person.”

The third factor, according to Fasano’s research is an “unusually permeable gut.” In fact, the author proposes that these three factors also underlie the pathogenesis of other autoimmune diseases, with of course triggers and genetic elements unique to those particular diseases. Fasano tells us that most non-celiacs have “tight junctions [that] ‘glue’ intestinal cells together.” On the other hand, in celiac patients, these links come apart, resulting in a small intestine from which pieces of gluten leak into the tissue and stimulate a response from immune cells. Fasano’s research regarding this third factor of pathogenesis offers hope of new prevention and treatment methods. He says, “Treatments that reduced leakiness could potentially ease not only celiac disease but also other autoimmune disorders involving unusually permeable intestines.”

This research into the leaky gut of celiacs can explain a question that has been perplexing researchers regarding the disease’s pathogenesis: Why do some people not develop celiac disease until later in life? According to Dr. Fasano, this issue could be associated with the microbes in the digestive tract. The microbicrobial population varies among individuals and groups and even over the course of one’s life.

“Apparently they can also influence which genes in their hosts are active at any given time,” he says. “Hence, a person whose immune system has managed to tolerate gluten for many years might suddenly lose tolerance if the microbiome changes in a way that causes formerly quiet susceptibility genes to become active.” Should this prove true, we may be able to prevent or treat celiac disease with probiotics.

A better understanding of the pathogenesis of celiac disease is certainly needed, but as of yet, researchers seem to be on their way to developing a full picture of what is involved in the origin and onset of the disease. By raising awareness and allocating more funding to celiac pathogenesis research, we may find ourselves with the ability to delay or even prevent the disease or with a new treatment option.

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Link Between Celiac And Diabetes

Type 1 diabetes and the food intolerance disorder celiac disease appear to share a common genetic origin, UK research suggests.

The genetic similarities are such it suggests they may also be triggered by similar environmental factors.

This raises the possibility that the protein gluten, already known to cause celiac disease, may also trigger Type 1 diabetes. The study appears in the New England Journal of Medicine.

Type 1 diabetes causes the body to attack the beta cells of the pancreas, limiting its ability to produce the insulin necessary to regulate blood sugar levels.

In contrast celiac disease attacks the small intestine. However, both conditions are the result of a malfunctioning immune system.

In addition, the development and anatomy of the small intestine and pancreas are closely related, and the gut immune system shares connections with pancreatic lymph nodes, which have been linked to an inflammation of the pancreas and the destruction of beta cells.

The researchers, from the University of Cambridge and Barts and The London School of Medicine and Dentistry, analyzed nearly 20,000 tissue samples to look for genetic similarities between the two conditions.

They identified seven chromosome regions that are shared between the two diseases.

The key regions are thought to regulate the mechanisms that cause the body’s own immune system to attack both the beta cells in the pancreas and the small intestine.

The researchers said more work was needed to pinpoint how genetic and environmental factors combined to trigger the conditions. The researchers stressed the interaction was likely to be complex, but suggested that the same sort of environmental factors were likely to trigger both conditions.

In the paper, they write: “Our results support further evaluation of the hypothesis that cereal and gluten consumption might be an environmental factor in type 1 diabetes, leading to the alteration of the function of the gut immune system and its relationship with the pancreatic immune system.”

Researcher Professor David van Heel said: “These findings suggest common mechanisms causing both celiac and Type 1 diabetes – we did not expect to see this very high degree of shared genetic risk factors.”

Karen Addington, of the Juvenile Diabetes Research Foundation, which helped fund the study, “These studies demonstrate that type 1 diabetes and celiac disease share far greater genetic overlap than had been appreciated; which helps explain the high prevalence of both conditions occurring simultaneously in an individual and may provide new avenues for understanding the cause and mechanisms of both conditions.”

Sarah Sleet, of the charity Celiac UK, described the research as a real advance in understanding a condition which is thought to go undiagnosed in many people.

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Celiac Guide

Celiac Disease

Celiac disease, sometimes also termed Celiac sprue or Gluten enteropathy, is a genetically influenced condition that results from eating gluten. More specifically, it is an ailment whereby the lining of the small intestine, called the intestinal mucosa, is chronically damaged by gluten proteins and their interaction with the immune system. It is identified by small intestinal villous atrophy that resolves when gluten is withdrawn from the diet. The illness may become apparent at any age, from infancy to old age, may remain asymptomatic, and may only be detected incidentally. Gluten is a group of proteins derived from wheat, barley and rye but not from oats, rice or maize. Alpha-gliadin is the most toxic portion of gluten.

The Celiac Iceberg

The condition is grossly under diagnosed, but we know that when actively looked for, incidence rates are between 1 in 100 to 200 people. There is a phenomenon called the Celiac Iceberg, and at the tip of the iceberg are those that are diagnosed with Celiac disease. There is a larger portion, nearly half, below them who have what is known as silent disease. More than half of all biopsy-proven Celiacs have no abdominal symptoms at all at the time of diagnosis, even though intestinal damage has been occurring for years. One might argue that if there are no symptoms, one should leave the patient alone with no intervention. Tragically, however, as discussed in many medical journals, the first signs of a problem in those with silent Celiac disease may be cancer. Finally there is a still larger base portion with latent disease. That is to say that if they were tested for antibodies for tissue transglutaminase (a marker for Celiac disease), they would test positive, but demonstrate no pathology, and yet years later Celiac disease may develop fully.


The symptoms associated with Celiac disease are many and varied, which is one of the reasons why it goes un- or misdiagnosed so often. The malabsorption resulting from Celiac disease causes diarrhoea and weight loss, although some recent commentators note an increasing number of untreated patients who are normal weight or overweight. Inability to absorb fats causes steatorrhoea, with bulky, pale, foul smelling stools that float in water due to their high fat content. Anaemia caused by iron deficiency is common, and the malabsorption of calcium and Vitamin D increases the risk of developing osteoporosis.

Patients may complain of abdominal pain and tiredness, while around 10% of patients present with neurological complaints, ranging from mild peripheral neuropathy to more severe central nervous system disturbance.

A small number of people present with a blistering rash, typically on elbows and buttocks, called dermatitis herpetiformis, which is associated with antibodies to tTG reacting with a form of this enzyme in dermal cells.

Possibly as a result of chronic inflammation, people with uncontrolled Celiac disease are at increased risk of developing intestinal neoplasms, particularly intestinal lymphoma. This risk is substantially reduced by strict adherence to a gluten-free diet.

All these signs and symptoms disappear when gluten is omitted from the diet, and reappear if it is reintroduced.

The American Journal of Gastroenterology notes that currently physicians do a poor job of diagnosing Celiac disease: only 50% of patients consider that they were diagnosed promptly; 27% consulted two or more gastroenterologists before diagnosis; and only 30-50% consider their Consultant knowledgeable about diagnosis and treatment.

Diseases and conditions associated with Celiac disease

  • Liver diseases
  • Irritable Bowel Syndrome
  • Microscopic colitis
  • Lymphocytic gastritis
  • Crohn’s disease
  • Ulcerative colitis
  • Dermatitis herpetiformis
  • Alopecia areata
  • Type 1 diabetes
  • Autoimmune thyroid disease
  • Addison disease
  • Arthritis
  • Osteoporosis
  • Sjogren syndrome
  • Chronic fatigue syndrome
  • Neuropathy
  • Chronic fatigue syndrome
  • Cerebellar ataxia
  • Iron deficiency
  • Epilepsy (with occipital calcifications)
  • Hyposplenism
  • Idiopathic dilated cardiomyopathy
  • Down syndrome
  • Autoimmune myocarditis
  • Turner syndrome

The incidence of concomitant Celiac disease occurring with most of these conditions is high enough (>5%) to warrant screening for Celiac disease in these patients. Screening should also be considered for first degree family members.


Small Intestinal Biopsy

The biopsy is simply a sample of the cells in the intestinal wall, an area that has a swift turnover of cells, and heals itself quite rapidly. In many, although not all cases, the intestine will appear perfectly normal after a couple of weeks on a strict gluten free diet.

The biopsy is taken by use of an endoscopy. This is a process whereby a small tube is passed down the throat, through the stomach, and into the small intestine. Tiny tissue samples are then taken from the intestinal wall for subsequent examination under a microscope. A normal biopsy will show many finger like projections from the surface of the intestinal wall. These are called villi, and increase the surface area of the intestinal wall available for absorption of nutrients. At least four biopsies should be taken, as villous atrophy is occasionally patchy. If the biopsy shows villous atrophy, crypt hyperplasia and increased intra-epithelial lymphocytes, and a gluten free diet leads to an improvement on a second later biopsy, then Celiac disease is the diagnosis.

Gluten challenge

This involves eating multiple daily servings of gluten rich foods, and then gauging the body’s reactions. This process is often undertaken by patients who have been on a gluten exclusion diet for a prolonged period of time. Dr James Braly notes that if a patient has already been on a gluten free diet, and the intestinal wall has started to heal, it can take a long period of time for sufficient damage to reappear in a biopsy.

Endomysium Antibody (EMA) testing

Endomysium is connective tissue found in the sheath of certain muscle fibres, and antibodies against this tissue are found in 90% of Celiacs who are consuming gluten; the antibodies disappear quite quickly after the exclusion of gluten. This test demonstrated that Celiac disease was an autoimmune problem by definition, since the antibodies attacked endomysium. The detection of these antibodies by immunofluorescence has a reported 85-98% sensitivity and 97-100% specificity.

Tissue Transglutaminase (tTG) Antibody testing

This type of test is fairly new on the scene. Transglutaminase is an enzyme that forms a part of endomysium and is involved in the repair of tissue. The tTG test identifies about 98% of those who have Celiac disease. It is commercially available as the Biocard Celiac Test. The detection of these antibodies using an ELISA assay is more sensitive but less specific than EMA (particularly in Down’s Syndrome and autoimmune disease).

IgA anti-gliadin antibody tests have moderate sensitivity but poor specificity, and their use is limited to the evaluation of symptomatic children under the age of two years.

Rectal Challenge

This delightfully titled test is a procedure that can be carried out in a doctor’s surgery, giving a clear result in a matter of hours. The test involves taking a biopsy of the rectal mucosa. Then gluten slurry is placed into the biopsy site, and another biopsy taken four or more hours later. Computer analysis will identify any immune reaction to gluten. The obvious criticism of this test is that it is both embarrassing and uncomfortable.

Management of Celiac disease

The recommended treatment is a gluten free diet (GFD) for life. Symptomatic improvement is reported with 70% of patients within two weeks. 85% of all patients respond to a GFD, although histological resolution may take 3-12 months. There is also now good evidence that this decreases the risk of small intestinal malignancy.

50% of patients with Celiac disease have secondary hypolactasia at diagnosis. Dairy products should be continued, and if they cause a problem, then ingestion of other foods high in calcium should be encouraged; alternatively use of a good bio-absorbable calcium supplement is recommended.
Iron and folate supplements are needed if there is a deficiency.

Gluten Free Diet (GFD)

A gluten-free diet means not eating foods that contain wheat (including spelt, triticale, and kamut), rye, and barley. The foods and products made from these grains are also not allowed. In other words, a person with Celiac disease should not eat most grain, pasta, cereal, and many processed foods. Despite these restrictions, people with Celiac disease can eat a well balanced diet with a variety of foods, including gluten-free bread and pasta. For example, people with Celiac disease can use potato, rice, soy, amaranth, quinoa, or bean flour instead of wheat flour. They can buy gluten-free bread, pasta, and other products from stores that carry organic foods, or order products from special food companies. Gluten-free products are increasingly available from health food stores and supermarkets.

Checking labels for “gluten free” is vital, since many corn and rice products are produced in factories that also manufacture wheat products. Hidden sources of gluten include additives such as modified food starch, preservatives, and stabilizers. Wheat and wheat products are often used as thickeners, stabilizers, and texture enhancers in foods.
The gluten-free diet is challenging. It requires a completely new approach to eating that affects a person’s entire life. Newly diagnosed people and their families may find support groups to be particularly helpful as they learn to adjust to a new way of life. People with Celiac disease have to be extremely careful about what they buy for lunch at school or work, what they purchase when food shopping, what they eat at restaurants or parties, or what they grab for a snack. Eating out can be a challenge. If a person with Celiac disease is in doubt about a menu item, ask the waiter or chef about ingredients and preparation, or if a gluten-free menu is available.

Gluten is also used in some medications. One should check with the pharmacist to learn whether prescribed medications contain gluten. Since gluten is also sometimes used as an additive in unexpected products, it is important to read all labels. If the ingredients are not listed on the product label, the manufacturer of the product should provide the list upon request. With practice, screening for gluten becomes second nature.

Foods to avoid

Grains, flours and breads
Wheat, rye, barley and possibly oats, millet and buckwheat. Beware of anything with malt added, as this is usually barley malt.

Fruit and Vegetables
All tinned fruit and vegetables should be considered suspect until you are sure that they do not contain preservatives, stabilisers, emulsifiers and a food starch with gluten in it.

Avoid luncheon meats, prepared sausages, breaded meats and tinned meats containing preservatives.

Avoid cheeses that contain preservatives, such as cheeses spreads and dips, unless you are sure that the preservative does not contain gluten.

Drinks and juices
Do not drink any instant coffee, tea, drinking chocolate or ground coffees that contain grain. Avoid all beers, ales and anything made from grain like whisky, bourbon and most liqueurs. Check processed fruit drinks in case they use a preservative containing gluten.

Salad dressings
Unless you are certain they are gluten free, avoid all commercial salad dressings.

Most tinned soups, soup mixes and gravy in powdered or cubed form are not gluten free.

Products prepared with grains are not allowed, as are ice cream and cones containing gluten, along with all commercial cake mixes and biscuits.

Watch out for curry powders, dry seasoning mixes, ketchups, mustards and horseradishes, chewing gum, vinegars, margarines, soy sauces made from wheat or MSG, and white pepper.

For comprehensive information on the GFD, including recipes, click here.