Celiac disease or leaky gut is a chronic digestive and immune disorder that damages the small intestine. The disease is triggered by gluten present in food. It is one of the most underdiagnosed hereditary autoimmune disorders.
Autoimmune disorder or autoimmunity is when the immune system fails to display self-tolerance and attacks the person’s own tissues. It is any pathological condition resulting from an individual’s immune response to its cells or tissues. Due to unknown environmental triggers and certain genes that increases susceptibility, the immune system of an autoimmune patient gets activated and starts producing self-reactive clones of T-cells and B-cells.
For those with celiac disease, the immune system treats gluten as a foreign body and inflames the villi of the small intestine to protect the body. The villi enables the body to digest and absorb food, but due to the reaction of gluten, it gets inflamed and eventually flattens.
In the case of celiac disease, the body damages or destroys the villi which is the most important component of the small intestine. The loss of villi reduces the surface area available for absorption and destroys the enzymes in the microvilli responsible for digesting and transporting nutrients.
Role of gluten protein
The main trigger of celiac disease is gluten, a group of proteins found primarily in wheat, rye, and barley. The composition of gluten is glutenin and gliadin. Normally when we digest protein, it is broken down in the stomach and small intestine into dipeptides or monopeptides that are readily absorbed by the small intestine. But the gluten molecule is resistant to enzymes that break down proteins (peptidases).
As a result, we are left with a long peptide chain, which is the toxic fraction of gliadin. This toxic fragment enter the intestine, especially underneath the epithelial cells lining the villi. People allergic to gliadin start developing an immunological reaction to this gliadin fraction which leads to inflammation and destruction of the villi.
The only definitive means of accurately diagnosing celiac disease is an intestinal biopsy, which is the gold standard. However, a specific blood test is an important indication of whether people have celiac disease.
- Blood tests- the blood test for diagnosing celiac disease is very specific and sensitive. This test serve as a first-line indicator of celiac disease. It includes detecting IgA (Immunoglobulin A) and tissue transglutaminase antibodies (tTG) in the blood sample. IgA endomysial antibodies (EMA) are highly specific markers for celiac disease. Based on the presence of IgA antibodies, the person can be classified as IgA deficient or not. IgA and IgG deaminated gliadin peptides in a blood sample may reveal whether a person has celiac disease.
- Endoscopy and Biopsy – the doctors will conduct a biopsy if the blood test is positive to confirm celiac disease. Endoscopy is a procedure in which a flexible tube (scope) is passed down the throat, through the stomach, and into the small intestine so that doctor can both visualize and perform biopsy of the areas. The patient has to fast for eight hours so that the stomach is empty. An IV is put in for sedation. A local anesthetic spray is used to reduce the gag reflex. The procedure takes 10-20 minutes and is conducted under conscious sedation.
Drugs used in the treatment and how they target the disease
- Genetically modified wheat- currently, experiments are going on to alter the grain by removing the toxic fragment. Thus, enabling people with celiac disease to eat wheat. Three variety of wheat was taken for the study; Triticum durum (UAS-428), Triticum dicoccum (DDK-1025), and Triticum aestivum (HD-285 NIAW-917). This modified wheat flour was used to make pasta. The gluten content in this modified wheat was found to be 48 ppm which is 99.95% lesser than normal wheat.
- Permeability Blockers- Larazotide is an eight amino acids containing peptide that prevents opening tight junctions induced by multiple stimuli, including cytokines, bacterial antigens, and gluten fragments. It serves as an inhibitor of intestinal permeability. This drug works on a ‘tight junction’ holding the cells together.
- Oral peptidases- researchers are investigating enzymes (oral peptidases or glutenases) that digest the toxic fraction of gliadin. If the enzymes supplied as medication could digest all these toxic fragments in the stomach, gluten will be safe to eat. Researchers have obtained different enzymes from diverse sources, including commercially available probiotics, fungi, and various bacteria and grains that can digest gluten.
- Cytokine Blockers– cytokines are protein messengers found in the body. In the presence of gluten, they are set off and continue the inflammatory reaction in the small intestine. Cytokines released from inflammatory cells damage the small intestine membrane, resulting in villous atrophy. Several cytokines are at work in the intestine such as Interleukin-15 (IL-15). Blocking IL-15 has the great potential for use in people with refractory celiac disease. Cytokine blockers have one disadvantage. Using them may increase our chances of getting a severe infection because they protect our body against disease.
The current scenario of celiac disease is that people are becoming more allergic to gluten, not able to digest gluten and thus face a serious problem. Going on a gluten-free diet can reduce the symptoms of celiac disease, but the introduction of genetically modified wheat and enzyme therapy can prove itself to be a permanent cure for the disease. These can be important tools for disease treatment and researchers must focus on these areas, as these tools can be effective.