Gluten Intolerance: What It Is, Symptoms, and How to Diagnose

Gluten is composed of various prolamins (storage proteins) primarily found in wheat, but it can also be found in barley, rye, and oats. The term gluten intolerance can refer to three types of conditions: 

1. Autoimmune celiac disease; 
2. Non-celiac gluten intolerance; 
3. Wheat allergy. 

Below, we delve deeper into each of the mentioned conditions. 

What is autoimmune celiac disease?

Celiac disease is an autoimmune condition, meaning the body’s own immune cells attack the body’s cells, resulting in an inflammatory process that can occur in both children and adults (1). 

This inflammation occurs in the small intestine, specifically in its inner lining, which leads to the atrophy of the villi of the small intestine, causing malabsorption of nutrients. 

This condition is induced by gluten-containing foods in individuals carrying the HLA-DQ2 haplotype (90% of cases) or DQ8 (6% of cases). This element, typically found in cereals such as wheat, barley, and rye, interacts with HLA markers, causing an abnormal immune response of the mucosa and consequent tissue damage. 

Next, understand more about the diagnosis, symptoms, and characteristics of celiac disease. 

How is celiac disease diagnosed? 

The diagnosis of celiac disease initially involves serological tests to assess antibodies (2): 

• Tissue transglutaminase antibody; 
• Endomysial antibody; 
• Gliadin antibody; 
• Immunoglobulin A. 

If the serology is positive, it is necessary to perform a duodenal biopsy to confirm the diagnosis. 

When to suspect celiac disease? See the most frequent symptoms 

In children, the most frequent symptoms of celiac disease are (3): 

• Abdominal pain and bloating; 
• Chronic diarrhea; 
• Vomiting; 
• Constipation; 
• Pale, foul-smelling, or fatty stools; 
• Iron deficiency anemia; 
• Weight loss; 
• Fatigue; 
• Irritability and behavioral problems; 
• Permanent dental enamel defects; 
• Delayed growth and puberty; 
• Short stature; 
• Growth deficiency; 
• Attention Deficit Hyperactivity Disorder (ADHD). 

In adults, the most common symptoms are: 

• Unexplained iron deficiency anemia; 
• Fatigue; 
• Bone or joint pains; 
• Arthritis, osteoporosis, or osteopenia; 
• Liver and bile duct disorders (transaminase elevation, hepatic steatosis, primary sclerosing cholangitis, among others); 
• Depression or anxiety; 
• Peripheral neuropathy (tingling, numbness, or pain in the hands and feet); 
• Seizures; 
• Migraines; 
• Menstrual period changes. 
• Infertility or recurrent miscarriages; 
• Aphthous ulcers and dermatitis herpetiformis (itchy skin rash). 

What is non-celiac gluten intolerance? 

Non-celiac gluten intolerance is diagnosed more frequently in adults than in children (4). The first cases of non-celiac gluten sensitivity (NCGS) were described as inconclusive pathology with symptoms of abdominal pain, discomfort, bloating, altered intestinal permeability, and fatigue, with the hypothesis of celiac disease being excluded. 

In this case, approximately 50% of individuals present with the HLA-DQ2 and/or HLA-DQ8 haplotypes (5). However, they do not have identified anti-transglutaminase antibodies. Thus, gluten only triggers an immune response, leading to increased expression of interleukins such as IL-6, IL-21, IL-17, and IFN-γ (6). 

It is speculated that the microbiota may also participate in the pathogenesis of non-celiac gluten intolerance. It is suggested that the composition of the intestinal microbiota and metabolic profiles may influence the reduction of gluten tolerance in genetically susceptible individuals (7). 

Patients with non-celiac gluten intolerance also present with nutritional deficiencies, other autoimmune diseases, and decreased bone mineral density compared to the general population. 

What are the main symptoms of non-celiac gluten intolerance?

The symptoms of non-celiac gluten intolerance are very similar to those of autoimmune celiac disease. Individuals suffering from this condition often experience (8): 

• Abdominal pain; 
• Bloating; 
• Altered intestinal permeability; 
• Diarrhea or constipation. 

Cases of gluten intolerance have been recognized as irritable bowel syndrome (IBS). In addition to intestinal symptoms, it is suggested that gluten-related peptides enter the systemic circulation, which can cause: 

• Neurological conditions such as ataxia; 
• Neuropathy; 
• Encephalopathy; 
• Depression; 
• Anxiety; 
• Autism; 
• Schizophrenia; 
• Psychosis.  

What is wheat allergy?  

Wheat allergy is an IgE-mediated food allergy and is one of the eight major food allergies. 

When an allergen binds to IgE antibodies, it induces the activation of mast cells and basophils. In the case of wheat, it is assumed that the allergy occurs due to an alteration in oral tolerance, and as a consequence of Th2 immune dysregulation, it induces sensitization and the production of allergen-specific IgE antibodies by B cells (9). 

Depending on the route of allergen exposure, wheat allergy can be classified as: 

• Occupational asthma (baker’s asthma) and rhinitis; 
• Food allergy, involving the skin, gastrointestinal tract, or respiratory system; 
• Exercise-induced wheat-dependent anaphylaxis; 
• Contact urticaria. 

It has a higher prevalence in children, including symptoms such as moderate to severe atopic dermatitis. Wheat ingestion can cause urticaria, angioedema, bronchial obstruction, nausea, abdominal pain, or in severe cases, systemic anaphylaxis (10). 

In adults, gastrointestinal symptoms caused by ingestion can be mild and difficult to recognize, with the most common symptoms being diarrhea and abdominal distension. 

In this scenario, SYNLAB not only provides serological measurements of anti-tissue transglutaminase, anti-endomysial, anti-gliadin antibodies, and immunoglobulin A, but also offers different innovative tests for the analysis of gluten intolerance or wheat allergy. 

What are the stools like for someone with gluten intolerance?

Stools of patients with gluten intolerance are often (3): 

• Pale; 
• Watery; 
• Bulky; 
• Foul-smelling — due to poor fat absorption. 

However, in some less frequent cases, the patient may experience constipation (11). 

What are the treatments for gluten intolerance?

The treatments and practices that can help manage this condition and improve quality of life include: 

Gluten-free diet 

The primary and most effective treatment for gluten intolerance is adopting a strictly gluten-free diet. This means eliminating all foods containing gluten, including bread, pasta, cakes, and many processed foods. Transitioning to a gluten-free diet can be challenging, but it is essential to avoid the damage that gluten can cause to the small intestine in people with celiac disease. 

In addition to avoiding gluten, it is important to ensure that the diet is nutritionally balanced and rich in vitamins and minerals. Many naturally gluten-free foods, such as fruits, vegetables, meats, fish, and dairy products, can provide the necessary nutrients. 

Furthermore, there is a growing variety of gluten-free products available on the market that are enriched with vitamins and fibers, helping to maintain a varied and nutritious diet. 

Medical and nutritional monitoring

Although a gluten-free diet is the central treatment for gluten intolerance, medical and nutritional monitoring is crucial. A gastroenterologist can perform tests to monitor intestinal health and adherence to the gluten-free diet. 

A nutritionist, on the other hand, is the professional who can provide guidance on the best food choices and ensure that the diet meets all the individual’s nutritional needs. 

It is also important to be aware of cross-contamination, which can occur when gluten-free foods come into contact with foods that contain gluten. This can happen in the home kitchen or in restaurants, so it is essential to take measures to avoid this contamination, such as using separate utensils and specific preparation areas for gluten-free foods. 

How to know which test to choose to find out if I have gluten intolerance?  

There isn’t a single test to diagnose gluten intolerance. A combination of clinical assessment and laboratory tests is necessary. Blood tests to detect antibodies such as anti-endomysial, anti-tissue transglutaminase, and anti-gliadin are common. 

To determine which test should be performed for the diagnosis of gluten intolerance, it is necessary to consider that the term can refer to two types of conditions: 

1. Autoimmune celiac disease; 
2. Non-celiac gluten intolerance. 

Therefore, only a specialist doctor can indicate which test should be done, considering the symptoms presented and the patient’s medical history. 

The SYNLAB Group, a leader in the provision of medical diagnostic services in Europe, performs a complete range of laboratory clinical analyses for patients, healthcare professionals, clinics, and the pharmaceutical industry. Below, see which tests the institution offers for identifying gluten intolerance. 

Gluten Intolerance Tests – see which ones SYNLAB offers for each condition related to the element

The tests that SYNLAB offers for analyzing gluten intolerance are: 

Gluten Intolerance Test: Celia Test

The Celia Test analyzes the following haplotypes: 

• HLA-DQ2, which is commonly associated with 90% of cases; 
• HLA-DQ8, typically related to 6% of patients with intolerance. 

The test is indicated for: 

• Individuals with clinical suspicion and negative serological study before performing duodenal biopsy; 
• Investigating genetic susceptibility in relatives of a celiac patient; 
• People with positive serological studies; 
• For those who follow a gluten-free diet without presenting a correct diagnosis; 
• Cases in which there is reintroduction of gluten after exclusion diet.  

Gluten and Lactose Intolerance Test: Intolerance 2 

The Intolerance 2 test allows you to know in a single analysis, through a simple blood collection, if there is a genetic predisposition to celiac disease by analyzing the HLA-DQ2 and HLA-DQ8 haplotypes, and also primary lactose intolerance by analyzing the -13910C>T variant in the MCM6 gene, responsible for the production of the lactase enzyme, associated with 90% of cases of lactose intolerance. 

The test is indicated for patients with: 

• Clinical suspicion of celiac disease and negative serological study before performing duodenal biopsy; 
• Positive serology for celiac disease that reject duodenal biopsy; 
• Symptoms compatible with celiac disease; 
• Symptoms compatible with lactose intolerance. 

Wellness Check

Through a simple blood collection, the Wellness Check test provides information about the genetic predisposition to metabolic regulation and processes related to the patient’s nutrition. This allows for planning an adequate and personalized diet. 

In addition to analyzing gluten intolerance by evaluating the HLA-DQ2 and HLA-DQ8 haplotypes, it determines genetic variants in 24 genes related to: 

• Cholesterol; 
• Caffeine metabolism; 
• Lipid profile; 
• Osteoporosis risk; 
• Liver detoxification; 
• Lactose intolerance; 
• Salt sensitivity; 
• Alcohol metabolism; 
• Oxidative stress; 
• Homocysteine metabolism; 
• Inflammatory response. 

The test is recommended for people who: 

• Wish to maintain and improve their current state of health, preventing, as much as possible, chronic diseases common in adulthood; 
• Have a family history of diseases common in adulthood; 
• Have disorders in neurological development or chronic diseases, in order to improve their quality of life through nutrition.  

Learn more about SYNLAB’s test at: Wellness Check – The genetics of metabolism, nutrition, and well-being. 

A200 test 

The A200 test evaluates the reactivity of IgG (hypersensitivity reaction) to gluten proteins and 216 other foods from the Mediterranean diet. With a simple blood collection, it is possible to know which foods may be potentially harmful to your health. 

The test is recommended for patients with gastrointestinal and musculoskeletal disorders, respiratory and dermatological diseases, neurological and psychological pathologies, among others. Some examples include: 

• Abdominal pain; 
• Constipation; 
• Diarrhea; 
• Bloating; 
• Gastritis; 
• Asthma; 
• Persistent cough; 
• Bronchitis; 
• Acne; 
• Eczema; 
• Urticaria; 
• Migraine; 
• Dizziness; 
• Anxiety; 
• Depression; 
• Hyperactivity; 
• Arthritis; 
• Fibromyalgia; 
• Fluid retention; 
• Obesity.  

What is the wheat allergy test?

 The test offered by SYNLAB for wheat allergy analysis is ISAC. 

The ISAC test involves the simultaneous determination of specific IgE antibodies to 112 allergenic proteins, present in over 50 different allergens, including wheat, from a single blood sample (plasma or serum). The analysis allows for obtaining an individual sensitization profile, and the results are classified into four categories: 

1. Undetectable reaction; 
2. Low; 
3. Moderate-high; 
4. Very high. 

The test is indicated for: 

• Individuals where no correlation is observed between the positivity of conventional allergy tests and symptoms; 
• Complex cases with an unsatisfactory response to treatment; 
• Evaluation of patients with idiopathic anaphylaxis; 
• Detection of suspected and unsuspected sensitizations.  

Become a partner of SYNLAB and expand your healthcare institution’s testing capabilities! 

The provision of accurate and up-to-date tests is essential for making more accurate diagnoses and for better treatment direction. SYNLAB is here to assist you. 

We offer diagnostic solutions with rigorous quality control to the companies, patients, and doctors we serve. With over 10 years in Brazil, operating in 36 countries across three continents, we are a leader in service provision in Europe. 

Get in touch with the SYNLAB team and discover the available tests. 

References 

1. AZIZ, I.; LEWIS, N. R.; HADJIVASSILIOU, M.; WINFIELD, S. N.; RUGG, N.; KELSALL, A.; NEWRICK, L.; SANDERS, D. S. A UK study assessing the population prevalence of self-reported gluten sensitivity and referral characteristics to secondary care. European journal of gastroenterology & hepatology, [S. l.], v. 26, n. 1, 2014. DOI: 10.1097/01.meg.0000435546.87251.f7.
2. CATASSI, C.; GATTI, S.; LIONETTI, E. World perspective and celiac disease epidemiology. Digestive diseases , [S. l.], v. 33, n. 2, 2015. DOI: 10.1159/000369518.
3. CHEHADE, M.; MAYER, L. Oral tolerance and its relation to food hypersensitivities. The Journal of allergy and clinical immunology, [S. l.], v. 115, n. 1, 2005. DOI: 10.1016/j.jaci.2004.11.008.
4. MAKHARIA, Archita; CATASSI, Carlo; MAKHARIA, Govind K. The Overlap between Irritable Bowel Syndrome and Non-Celiac Gluten Sensitivity: A Clinical Dilemma. Nutrients, [S. l.], v. 7, n. 12, p. 10417, 2015.
5. Disponível em: https://www.scielo.br/j/ramb/a/Gh38SVTy6nzPzNxzsPHzwFv/?format=pdf&lang=pt. Acesso em: 15 fev. 2023.
6. RAMESH, S. Food allergy overview in children. Clinical reviews in allergy & immunology, [S. l.], v. 34, n. 2, 2008. DOI: 10.1007/s12016-007-8034-1.
7. SANDERS, D. S.; AZIZ, I. Non-celiac wheat sensitivity: separating the wheat from the chat! The American journal of gastroenterology, [S. l.], v. 107, n. 12, 2012. DOI: 10.1038/ajg.2012.344.
8. SAPONE, A. et al. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC medicine, [S. l.], v. 9, 2011. DOI: 10.1186/1741-7015-9-23.
9. Symptoms of Celiac Disease. [s.d.]. Disponível em: https://celiac.org/about-celiac-disease/symptoms-of-celiac-disease/. Acesso em: 15 fev. 2023.
10. VOLTA, Umberto; BARDELLA, Maria Teresa; CALABRÒ, Antonino; TRONCONE, Riccardo; CORAZZA, Gino Roberto. An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity. BMC medicine, [S. l.], v. 12, n. 1, p. 1–8, 2014.
11. BOÉ, Cristiane; LOZINSKY, Adriana Chebar; PATRÍCIO, Francy Reis; ANDRADE, Jacy Alves B. De; FAGUNDES-NETO, Ulysses. Doença celíaca e constipação: uma manifestação clínica atípica e pouco frequente. Revista Paulista de Pediatria, [S. l.], v. 30, n. 2, p. 283–287, 2012.