Written By Dr Senani Wijesena – 23/05/2016
Celiac disease is a chronic small bowel disorder characterized by inflammation, mal-absorption and chronic gastrointestinal symptoms in untreated individuals. Gluten intolerance which is characterized by an immune reaction to gluten causes similar effects on the bowel as celiac disease, although of a milder nature.
Gluten sensitivity/intolerance is increasingly common in today’s society occurring in at least 6% of the population with an additional 1-3% being diagnosed with celiac disease. Although many individuals with gluten intolerance carry the celiac genotypes HLADQ2/D8, not all do and the mechanism underlying the reaction to gluten by the immune system seems to be of different type between celiac disease and non-celiac gluten sensitivity (gluten intolerance).
Both celiac disease and gluten intolerance have been associated with an increased risk of several health problems (of variable magnitude), including nutritional deficiencies, anemia, autoimmune disease, cancer, asthma, hay fever, dermatitis, osteoporosis, irritable bowel syndrome, mood disorders (depression), schizophrenia, autism and ADD (attention deficit disorder) amongst others.
History of gluten inclusion in human diets
Gluten was not always found in human diets and was introduced about 10,000 years ago with agriculturisation and growing of grains such as wheat. Wheat first originated in south western Asia, and then was adopted in Iraq, Syria, Jordon and Turkey. Archeological findings show that wheat crops were grown in the Nile Valley about 5,000 B.C. as well as in India, China, and even England at about the same time.
Certain ethnic groups are at higher risk of Celiac disease and gluten sensitivity than others e.g. the Irish and those of Irish descent as well as Scandinavians, Italians, British, Spaniards, Jews, and Palestinians. It has been estimated that 1 in 100 people in many European countries will eventually develop Celiac disease. The disease has also been described, in populations from South America, Eastern Europe, the Near East, Pakistan, Cuba, and North Africa. Celiac disease is a heritable condition.
It is believed that the higher prevalence of celiac disease across Europe is related to the interaction between genetic gradients, largely determined by the advance of agriculture, and historical patterns of cereal ingestion.
Australia and the U.S.A were introduced to wheat in the years 1790 and 1777 respectively. Both populations have a high number of early settlers of Irish descent as well as Italian, hence, gluten sensitivity and celiac disease is found in high frequency in these countries.
The high incidence of gluten sensitivity in certain populations in modern society appear to be due to the fact that genetic adaptation to environment and dietary changes are known to occur slowly in humans and can take up to 100,000 years. Hence, as wheat, related grains and gluten was only introduced 10,000 years ago, humans have not yet been able to adapt to the new introduction of these food constituents.
What is Gluten?
Gluten is a protein found in the grains-wheat, rye, oats, barley, spelt, triticale, kamut and contains the fractions, prolamine and glutenin.
Wheat prolamines can be sub-fractionated into alpha, beta, gamma and omega gliadins, all of which are harmful to susceptible intestinal mucosa with the alpha type being the most severe. Gliadin that has been subjected to complete hydrolysis (breakdown), however, does not activate celiac disease in susceptible individuals. Rice, corn and oats have a lower prolamine content and of a different type than wheat, barley and rye and may be better tolerated in some individuals.
Gluten causes inflammation in the mucosal lining of the intestine meditated by lymphocytic immune cells due to an immunological cross-reaction between the gluten antigen and intestinal/self antigens. This cross-reaction is enhanced by a particular genetic predisposition (HLA DQ2/HLADQ8 genetic type) in susceptible individuals.
Celiac disease versus NCGS
Celiac disease is a chronic small bowel disorder caused by an abnormal immune response to an array of antigens of gluten and related prolamines of wheat, rye and barley in genetically susceptible individuals who express the HLA-DQ2/DQ8 genetic type. Gluten peptides are efficiently presented by celiac disease-specific HLA-DQ2- and HLA-DQ8-positive antigen presenting cells to the immune system i.e. CD4+ T-cells (lymphocytes) that, once activated, drive a T helper cell type 1 (inflammatory) response leading to the development of the typical celiac lesion.
The lesion includes flattening of the lining of the small intestinal villi, crypt hyperplasia and infiltration of inflammatory cells. These small intestinal changes can be identified on biopsy and confirms the diagnosis. The inflammation occurring in celiac disease classically produces a malabsorption syndrome, with diarrhea, fatty stool and loss of weight or failure to thrive. Deficiencies of the fat-soluble vitamins D, E, A, and K; iron; folic acid and calcium are also common.
The genotype HLA-DQ2 occurs in 95% of individuals with celiac disease and DQ8 in the remainder and testing of individuals for these markers can occur via blood tests. Not all individuals who carry these genes, however, express the full syndrome of Celiac disease and may have gluten intolerance instead or have no reaction to gluten. Inheritability hence is not 100%.
Celiac disease is characterized by specific autoantibodies (which may be measured on blood tests) against the enzyme tissue transglutaminase (anti- tTG), gliadin (anti-gliadin antibodies) and endomysium (anti-endomysial antibodies). Since gliadin peptides are excellent substrates for tTG, which adds a negative charge to the peptide that causes it to have a much higher affinity for the HLA-DQ2 and HLA-DQ8 molecules, the action of tTG is believed to be a key step in the pathogenesis of celiac disease.
Celiac disease is characterized by malabsorption and an abnormal small intestinal structure that reverts to normal on removal of dietary gluten. Dietary gluten exclusion is also associated with a fall in the serum level of anti-tTG antibodies to somewhat un-detectable levels.
Individuals with Celiac disease have an increased risk of autoimmune diseases such as dermatitis herpetiformis, intestinal lymphoma, insulin dependent diabetes (type 1), Hashimoto’s thyroiditis, inflammatory bowel disease, Sjogren’s disease, rheumatoid arthritis, systemic lupus erythrematosus (SLE), Inflammatory bowel disease, autoimmune hepatitis, IgA (antibody) deficiency and sclerosing cholangitis. The gene type that is carried by those with celiac disease also increases the risk of these autoimmune conditions.
Celiac disease increases the risk of developing other secondary food intolerances and allergies including lactose intolerance as well as osteoporosis, gastrointestinal cancer, pancreatic insufficiency, anemia, multiple sclerosis, neuropathy, depression, alopecia (hair loss), mouth ulcers, infertility, recurrent miscarriage, lymphoma, down’s syndrome, turner’s syndrome and pneumococcal pneumonia.
Studies have shown that breastfeeding decreases the risk of developing celiac disease as does restricting quantities and delaying the introduction of gluten and cereal grains in the infants diet. The early introduction of cow’s milk has also been found to play a major causative role in the expression of celiac disease.
Other factors may have a role in precipitating symptoms. These include gastrointestinal surgery, pregnancy, high-dose gluten challenge, and viral infection, which may heighten the immunologic response to gluten, thus extending the disease distally and causing clinically apparent decompensation.
Non- Celiac Gluten sensitivity or gluten intolerance is a condition characterized by clinical signs and symptoms induced by gluten but without the same diagnostic criteria (genetic, serology, biopsy changes) as celiac disease and in which allergic and autoimmune mechanisms have been excluded. More specifically, patients have negative serological (blood) tests for coeliac disease (endomysial and/or tissue transglutaminase antibodies) but anti-gliadin antibodies may be present. The duodenal (upper small intestine) mucosa is grossly normal on biopsy and they have variable presence of the genetic type HLADQ2/8.
The Celiac disease-predisposing HLADQ2 and DQ8 genotypes are found in 50% of NCGS patients, a prevalence that is lower than celiac disease (95%) and only slightly higher than the general population (30%).
Symptoms should resolve on a gluten free diet and reappear on gluten challenge. It is essentially a diagnosis of exclusion. Classical signs and symptoms of gluten intolerance include typical IBS-like symptoms such as bowel irregularity, bloating, constipation, diarrhea, abdominal cramping/pain, and systemic manifestations such as, “foggy head”, headache, fatigue, joint/muscle pain, leg or arm numbness, dermatitis (skin rash), depression and iron insufficiency/anemia. These symptoms and signs also occur in individuals with Celiac disease.
Symptoms occur within a few hours to days of ingestion of gluten, disappear with gluten withdrawal and relapse following gluten challenge.
The type of inflammation in the intestinal mucosa of individuals with gluten intolerance is considered slightly different to that of those with celiac disease and may be due to other types of low molecular weight wheat proteins rather than gliadin (gluten fractions) in some individuals. It may be caused by mal-digestion of the gluten protein. Recent studies raised the possibility that, besides gluten, wheat amylase-trypsin inhibitors (type of protein in wheat) and low fermentable, poorly absorbed, short chain carbohydrates (fructans/FODMAPS) can contribute to symptoms (at least those related to IBS) experienced by NCGS patients.
In addition to reactions to different wheat proteins in those with gluten intolerance, a different immunological reaction to gluten seems to occur in these individuals compared to those with celiac disease and involves a different component of the immune system (innate rather than adaptive immune responses). Wheat allergy is also different to both celiac disease and gluten sensitivity and involves an IgE immune response (acute with eosinophils/histamine release) to wheat proteins rather than an IgG delayed response which is characteristic of the later two conditions.
There is a link between NCGS and Irritable bowel syndrome and Hashimotos thyroiditis. Several studies have also suggested a relationship between NCGS and neuropsychiatric disorders such as Autism and Schizophrenia. Both Celiac disease and NCGS are associated with increased small intestinal permeability (‘Leaky Gut syndrome’), due to damage to the connective tissue/intercellular junctions between the small intestinal cells.
Increased intestinal permeability may be one mechanism associated with increased susceptibility to the autism spectrum disorders due to opioid dietary peptides (such as gluten and casein) crossing the intestinal membrane, entering the blood stream, crossing the blood brain barrier and affecting the endogenous opiate system and neurotransmission within the nervous system. The resulting excess of opioids is thought to lead to behaviors noted in autism such as hyperactivity, aggression, anxiety, depression, language and social impairment. Studies have shown gluten free, casein free (milk free) diets in some individuals with autism spectrum are associated with an improvement of intestinal permeability and behavioral symptoms. Increased intestinal permeability is also considered to be an underlying mechanism for other autoimmune diseases in general.
Celiac disease occurs in 1% of the general population (based on diagnostic criteria) but may be as high as 1 in 33 individuals. The overall prevalence of NCGS (gluten intolerance) in the general population is largely unknown, mainly because many patients are currently self-diagnosed and start a gluten free diet without medical advice or consultation. However, new data confirm that this is not an uncommon disorder.
Reports/studies show a wide variation in prevalence of NCGS from 3% in a study by Volta et al to 6% in a US referral center study. A U.K-based population study showed that 13% considered themselves as gluten sensitive and 3.7% consumed a gluten free diet. In New Zealand, 5% of children are on a gluten free diet. According to recent population based surveys performed in Northern Europe, the prevalence of IBS in the general adult population is 16-25% and of these approximately 1/3 report gluten sensitivity.
Although risk factors for NGCS have not yet been identified, the disorder seems to be more common in females and in young/middle age adults.
More studies are needed to further evaluate the condition Non-celiac gluten sensitivity (gluten intolerance).
Once the diagnosis has been established, a gluten free diet is indicated. This diet does not contain any wheat (including couscous and semolina), rye, barley, triticale, spelt, kamut and oats. Buckwheat and millet are often excluded as well.
Although buckwheat is not in the grass family and millet appears to be more related to corn and rice, buckwheat and millet contain prolamines with similar antigenic activity to the alpha-gliadin of wheat.
In addition other foods should be rotated (not eaten on a daily basis to reduce reactivity), and milk and milk products should be eliminated until the individual re-develops intestinal structure and function returns to normal.
Usually clinical improvement will be apparent within a few days or weeks (30% respond within 3 days, another 50% within one month and 10% within another month). 10% of patients, however, only respond after 24 to 36 months of gluten avoidance.
In addition to following a gluten free diet, patients should be tested and treated for nutrient deficiencies such as zinc, iron, and vitamin B12 as these may be low in people with maldigestion/malabsorption. Other supplements that may be given to assist with recovery from Celiac disease include digestive enzymes and probiotics. Pancreatic insufficiency (and associated maldigestion) has been found in 8-30% of celiac patients. Probiotics assist with improving the immune system in the gastrointestinal tract and can assist with reducing immunological reactions to gluten and other food intolerances.
Treatment for gluten intolerance follows the same principles as for celiac disease and requires a gluten free diet, nutritional supplementation as required and support for digestion/gut immunity with digestive enzymes and probiotics if needed.
Increased intestinal permeability seems to be lower in severity than in individuals with celiac disease as is inflammation in the intestinal mucosa which may account for less severe effects on nutritional balance/digestion and association with other illnesses compared to celiac disease.
Full assessment of individuals with suspected gluten intolerance and celiac disease include comprehensive blood tests, stool testing (functional and microbiological), and genetic typing.
Consultation with an Integrative Medicine practitioner or a Naturopath is recommended to assess, diagnose and treat these conditions.
Glossary of terms
Antigen– a molecule capable of inducing an immune response on the part of the host organism.
Hyperplasia– the enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells.
Crypt– mucosal glands of the intestine
Mucosa-A mucous membrane or mucosa is a membrane that lines various cavities in the body and surrounds internal organs.
Peptides– small proteins
Malabsorption– impaired absorption of food material/nutrients by the small intestine.
Autoimmunity and Autoimmune disease– the system of immune responses of an organism against its own healthy cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease.
Innate immune responses– refers to nonspecific defense mechanisms that come into play immediately or within hours of an antigen’s appearance in the body. These mechanisms include physical barriers such as skin, chemicals in the blood, and immune system cells that attack foreign cells in the body.
Adaptive immunity– There are two types of adaptive immune responses: humoral immunity, mediated by antibodies produced by B lymphocytes, and cell-mediated immunity, mediated by T lymphocytes.
Dermatitis herpetiformis– chronic, blistering skin condition
Hashimoto’s thyroiditis– autoimmune disease of the thyroid leading to inflammation and altered thyroid function
Sclerosing cholangitis is a disease of the bile ducts that causes inflammation and obliterative fibrosis of bile ducts inside and/or outside of the liver.
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