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Coeliac disease

Coeliac disease (also known as sprue) is a chronic inflammatory autoimmune condition of the intestine. In genetically predisposed individuals, the consumption of gluten-containing food triggers inflammatory reactions in the intestine. These inflammations lead to characteristic lesions of the small intestinal mucosa, which can progress to complete villous atrophy (tissue wasting). According to the Marsh classification for the histological assessment of intestinal biopsy samples, at least a type II mucosal alteration must be present to confirm the diagnosis. Coeliac disease can occur at any age, although the incidence is significantly higher in children than in adults. It is also more than twice as common in women as in men.

Problem Case: Wheat – What makes us ill?

Wheat, along with maize and rice, is one of the most important cultivated crops of our time. To meet demands such as continual yield increases, reduced use of pesticides, or adaptation to climate and environmental conditions, wheat breeding has been continuously advanced. Modern breeding and cultivation practices, along with industrial processing, have altered the protein composition of wheat and increased the proportion of immunoreactive components.

In genetically predisposed individuals, symptoms are triggered by the ingestion of gluten, a protein complex found in many grains. Grains with particularly high gluten content include:

  • Wheat
  • Barley
  • Rye
  • Spelt
  • Kamut
  • Einkorn
  • Emmer

Unlike grain allergies, coeliac disease is a chronic inflammatory autoimmune condition of the intestine caused by a misguided immune response to the grain component gluten.

Symptoms of Coeliac Disease

The symptoms are primarily due to impaired nutrient absorption and manifest as deficiency-related signs such as:

  • Weight loss
  • Anaemia
  • Protein deficiency oedema
  • Fatty stools (steatorrhoea)

The range and severity of clinical symptoms can vary significantly. In young children, the full expression of the disease typically includes:

  • Distended abdomen
  • Diarrhoea
  • Muscle wasting (hypotrophy)
  • Loss of appetite (anorexia)
  • Behavioural changes (e.g. increased crying or irritability)
  • Iron deficiency
  • Growth retardation

In paediatrics, coeliac disease should always be considered when there are unexplained developmental or growth disturbances.

Micronutrient Deficiencies in Coeliac Disease: Causes of Secondary Conditions and Complications

As described above, the disease is characterized by chronic inflammation of the small intestine, which typically leads to atrophy of the intestinal mucosa. This mucosal damage is associated with impaired absorption and uptake of micronutrients. Common deficiencies in coeliac patients often include:

  • Zinc
  • Iron
  • Vitamin A
  • Vitamin B12
  • Folic acid
  • Calcium
  • Vitamin D
  • Vitamin B3

Such deficiencies may result in further secondary conditions and complications, including:

  • Iron deficiency anaemia
  • Fertility issues
  • Migraine
  • Osteoporosis

Coeliac Disease and Autoimmune Disorders

It is notable that many affected individuals also suffer from additional autoimmune disorders. One of the most frequent comorbid conditions is Type 1 diabetes mellitus, which affects around 5 to 10% of individuals with coeliac disease. Conversely, many patients with Type 1 diabetes may have undiagnosed coeliac disease. Another autoimmune disorder frequently associated with coeliac disease is Hashimoto’s thyroiditis (chronic autoimmune thyroid disease).

Diagnosis of Coeliac Disease

There is no single definitive test for diagnosing coeliac disease. The diagnostic approach includes both laboratory-based (serology, molecular genetics) and clinical (histology) investigations. A confirmed diagnosis typically relies on the following findings:

  • Clinical examination and compilation of a medical history (including family history)
  • Serological detection of specific antibodies
  • Molecular genetic identification of risk HLA alleles (HLA-DQ2 / HLA-DQ8)
  • Small intestine biopsy (histological evidence of a specific enteropathy)

Comprehensive Diagnostic Scheme for Suspected Coeliac Disease

Non-coeliac Wheat Sensitivity

Non-coeliac wheat sensitivity is present when symptoms similar to the ones of coeliac disease or wheat allergy occur, but have been definitively shown not to be caused by an autoimmune or allergic reaction.

Symptoms

The clinical picture of non-coeliac wheat sensitivity is not clearly defined. Affected individuals report gastrointestinal symptoms (e.g. diarrhoea, abdominal pain, bloating) after consuming foods containing gluten or other wheat proteins. Extra-intestinal symptoms may also occur. These include:

  • Headaches
  • Fatigue
  • Dizziness
  • Joint and muscle pain
  • Skin changes
  • Anaemia
  • Depression

In children, gastrointestinal symptoms and tiredness are typically more pronounced. Symptoms usually subside once wheat-containing foods are eliminated from the diet.

Possible Causes of Non-coeliac Wheat Sensitivity

Potential triggers—distinct from gluten—include other wheat components such as:

  • Amylase-trypsin inhibitors (ATIs)
  • Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs)
  • Wheat germ agglutinins

Amylase-trypsin Inhibitors (ATIs)

ATIs are proteins produced by plants to protect against pests. They activate innate immune cells in the intestine. The resulting intestinal inflammation can spread throughout the body and trigger a coeliac-like clinical picture. Existing inflammatory diseases (e.g. multiple sclerosis) may also be exacerbated.

FODMAPs

FODMAPs (fermentable oligo-, di-, monosaccharides and polyols) are a group of carbohydrates which are poorly absorbed in the small intestine. Instead, they pass into the large intestine, where they are fermented by intestinal bacteria. Gases are produced as by-products of this process. They can cause symptoms such as:

  • Diarrhoea
  • Constipation
  • Bloating
  • Stomach pain
  • Nausea

Foods high in FODMAPs include:

  • Gluten-containing grains (wheat, barley, rye, spelt)
  • Fruits such as apples, apricots, cherries, mangoes, peaches
  • Vegetables and legumes like cauliflower, beans, chicory, garlic, onions
  • Dairy and milk alternatives (e.g. soya milk) containing lactose
  • Beverages such as strong brewed tea, fruit juices, lemonade, wine
  • Processed foods with additives like glucose-fructose syrup

A low-FODMAP diet is recommended if non-coeliac wheat sensitivity is suspected.

Wheat Germ Agglutinins (WGAs)

Non-coeliac wheat sensitivity can also be triggered by plant lectins. These are protective proteins found in many plants. The lectin found in the germ of cereal grains is called wheat germ agglutinin (WGA). Recent studies suggest that WGAs may be involved in gastrointestinal disorders by damaging the intestinal epithelium and thus increasing intestinal permeability. This effect may be worsened in individuals with pre-existing mucosal damage (e.g. “leaky gut” syndrome).

Therapeutically, the avoidance of wheat products is advised for individuals that are sensitive to WGA. Despite its name, WGA is not exclusive to wheat – other grains (including whole and sprouted varieties), peanuts, legumes, and nightshade vegetables (e.g. tomatoes, peppers) are also high in lectins. Overall lectin consumption should therefore be reduced.

Diagnostics

Due to the varied symptoms and possible triggers, diagnosis of non-coeliac wheat sensitivity begins with diagnosis by exclusion:
Coeliac disease and wheat allergy must first be ruled out. The diagnosis can then be supported by a controlled elimination followed by a reintroduction (provocation) of gluten/wheat products.

Further laboratory analyses help narrow down possible causes. However, a positive result does not confirm non-coeliac wheat sensitivity on its own.

Overview of Possible Laboratory Analyses

Amylase-trypsin Inhibitors

FODMAPs

Wheat Germ Agglutinins

FABP-2

H2 breath test

Wheat germ agglutinin antibodies (anti-WGA-IgG)

sCD14

Microbiota

 

Zonulin