Gluten: Allergy, intolerance or sensitivity?

What is gluten?

Gluten is a general name for the proteins (gliadins or prolamins and glutenins) naturally present in the seeds of many cereal grains (wheat, spelt, durum, barley, kamut, rye, oats).  

It is a sticky substance (etymologically speaking, "gluten" comes from the Latin "glu", meaning "glue, gum") that is formed during the hydration of flours (derived from milling grains) and plays a role in the making of doughs, particularly for its visco-elastic properties. Before becoming a controversial substance, gluten is an essential element in the art of baking. Indeed, gluten is indispensable in bread, an important staple in many cuisines. It can be attributed with the remarkable properties of making bread dough voluminous, elastic and resistant.

And it should be mentioned that this has not escaped the notice of the food industry: from its role as a thickener in dishes prepared in sauces, to its status as an ingredient in syrups and various drinks, gluten is an integral part of our diet. It even has the role of excipient (component of a drug other than the therapeutic molecule) in the pharmaceutical industry, where it is called "wheat starch". But don't panic, the FDA has released guidance on the amounts of gluten in drug products and its labeling, meaning that it is subject to increased surveillance because of its highly allergenic nature.

When should we use the term "gluten intolerance" versus "celiac disease"?

Using the term "food intolerance" when talking about celiac disease is a bit of a misuse of language. It is important to know that celiac disease is a chronic autoimmune disease induced by the ingestion of gluten. Whereas a food intolerance, strictly speaking, only causes digestive symptoms but does not involve the immune system.

Indeed, in certain people (who are genetically predisposed), the introduction of gluten to the intestinal mucous membrane causes such an inflammatory reaction that it leads to the shortening of the villi lining the small intestine. Consequently, this villous atrophy is often responsible for malabsorption, meaning that the body has difficulty absorbing nutrients, vitamins and minerals, which can lead to mild to severe deficiencies and certain complications depending on the extent of the disease.

Examples include anemia caused by an iron deficiency or by a folate (vitamin B9) or vitamin B12 deficiency. Vitamin D deficiency can also occur, which lead can lead to osteoporosis (bone demineralization).

In order to understand the inflammatory reaction at the origin of celiac disease, we must first understand the mechanism of the disease. When consumed, the body recognizes gluten as a "foreign" substance, i.e. one that must be eliminated. This explains the inappropriate reaction of the immune system (which is the very principle of an autoimmune disease), which produces antibodies (also called immunoglobulins or Ig) capable of recognizing, memorizing and neutralizing the element identified as "foreign": gluten. In celiac disease, it is the IgG and IgA antibodies that are involved.

What is the difference between a gluten allergy and a wheat allergy? 

What is known as gluten allergy actually refers to wheat allergy, which includes two types of reactions: reactive asthma caused by inhaling flour, known as baker's asthma, and the commonly accepted hypersensitivity reaction, known as food allergy.

The hypersensitivity reaction will be discussed in more detail later in this article. It is important to note, however, that wheat flour is one of the more common causes of occupational asthma in the US, following chemical dusts and vapors like isocyanate, a chemical used in car manufacture and repair, and animal substances such as dander, hair, and mites. Baker's asthma is considered a work-related allergy and asthma, and approximately 17% of all adult-onset cases are related to occupational exposures.

How are gluten allergy, gluten intolerance and celiac disease different?

Allergy (or hypersensitivity) to gluten is more rare and should not be confused with gluten intolerance. Indeed, the mechanism of gluten allergy is not quite the same. Allergy, like celiac disease, is based on the ability of the immune system to recognize gluten (identified as a "foreign" substance to the body) and to use antibodies (Ig) to neutralise it in a targeted manner. Gluten intolerance involves a long-term response with IgG and IgA, whereas allergy is a rapid response (within minutes to hours) mediated by IgE (immunoglobulins specific to the allergic response). Allergy is known as IgE-dependent.

To clarify the immunological mechanism of allergy, we should bear in mind that there are two phases:

• Sensitization: This constitutes the first contact with the allergen. The first time a patient allergic to gluten eats a piece of bread, the allergy has not yet developed. It is during this phase that the cells of the immune system (called mast cells) identify the "gluten" element as "foreign". These mast cells will activate on contact with the allergen and will become capable of producing the IgE antibodies called plasma cells. These IgE's are specific for the "gluten" allergen (they only recognize gluten) and will activate other immune cells so that they in turn become allergen-specific.
• Re-exposure to the allergen: This refers to the subsequent contact with gluten manifests itself through symptoms. In this phase, the immune cells (continuously circulating throughout the body) have been sensitized to the allergen, which they will identify in a rapid and targeted manner. Contact with the allergen causes the immune cells to release compounds, including histamine, which is responsible for all kinds of allergic symptoms.

These allergic symptoms are immediate and can range from skin reactions (hives, itching, dermatitis, swelling of the extremities, angioedema, etc.), digestive (abdominal pain, vomiting), respiratory (rhinitis) and cardiovascular (hypotension) reactions, to anaphylactic shock (the most serious terminal stage of anaphylaxis). Unlike the inflammatory reaction of celiac disease, allergic reaction does not induce villi atrophy.

What is gluten sensitivity? (Also called non-celiac gluten sensitivity (NCGS))

The NCGS is a clinical entity first described in scientific literature in the 1980s. It encompasses several clinical forms, notably those presenting clinical digestive (abdominal pain, bloating) and extra-digestive (fatigue, headaches, eczema) symptoms secondary to gluten consumption but without the anti-transglutaminase antibodies specific to celiac disease.

In contrast to celiac disease and gluten allergy, there is no recommended or established test or histological criteria for diagnosis. Rather, it is an exclusionary diagnosis, i.e. the diagnosis is made once allergy and gluten intolerance have been ruled out.

Because of this, it is for this population that recommendations and indications for a gluten-free diet are less straightforward. In the literature, there are many cases in favor of the benefits of a gluten-free diet, but the question arises as to whether these clinical improvements are not as much related to the avoidance of other non-gluten wheat compounds. Indeed, other substances are suspected to be involved in the occurrence of a NCGS. Thus, the causes and origins of the disease are poorly known and there is little literature available on the subject. We know that this condition explains the presence of digestive and extra-digestive symptoms in patients not diagnosed as celiac or allergic to gluten, but it merits further investigation.

To learn more:

The gluten-free diet has also appeared in the sporting world as an "enhancer" of physical performance. Faced with this popular belief, the French INRAE (National Research Institute for Agriculture, Food and the Environment) has set up a study in Clermont-Ferrand to determine the real impact of the gluten-free diet on top-level sportsmen and women. The project, called “GlutHealth”, aims to demystify the gluten-free diet and to provide scientific evidence that could benefit the sporting community, which is not spared from gluten-related illnesses.

The media coverage of the gluten-free diet has, on the one hand, made it possible to diagnose celiac disease patients more often, but on the other hand, has fueled the demonization of gluten.

The current recommendations therefore attempt to establish the scientific basis for the gluten-free diet, which must be implemented in a safe manner.

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