Celiac Disease: Treatments Beyond the Gluten-Free Diet

Celiac disease is an inflammatory autoimmune condition triggered by the ingestion of gluten, a protein found in cereals such as wheat, rye, and barley. This disease causes underlying damage to the mucosal lining of the small intestine, leading to flattening of the villi, the small hairlike projections of the intestine that facilitate nutrient uptake. In the long term, this damage can lead to malabsorption of nutrients. A person with this condition also experiences symptoms like diarrhea, bloating, abdominal discomfort, and fatigue. 

Histopathology of villous atrophy in celiac disease, GeneFood. Wikimedia, 2022. Creative Commons License.

As of now, the only effective treatment for celiac disease is a strict gluten-free diet. This diet often comes with challenges like the risk of gluten contaminating otherwise safe food, increased expense of purchasing gluten-free products, isolation during social events involving food, and stigmatization. 

Imagine having to be cautious at every meal to avoid even small traces of gluten, which can cause debilitating symptoms and intestinal damage. This is the reality for people with celiac disease. Researchers are working to develop novel ways of managing the disease, with the hope of removing the need for this burdensome diet. Popular treatment approaches include enzymatic degradation of gluten, gluten sequestration, and strategies to induce gluten tolerance. 

Enzymatic degradation approaches use enzymes to break gluten into smaller pieces, which ideally would be unrecognizable to the immune system. Enzymes that function in the stomach’s acidic environment, efficiently bind to and break down gluten, and resist degradation by other digestive enzymes, are good for this approach. 

Scientists have tested bacterial, plant, and fungi-derived enzymes meeting these criteria. For example, the fungi-derived AN-PEP (Aspergillus niger prolyl endopeptidase) is currently available as a dietary supplement. While clinical trials showed this enzyme has a marked impact on gluten digestion, later studies found no significant difference in relevant biomarkers between patients who supplemented with this enzyme versus a placebo. A clinical study reported that patients who took AN-PEP described less severe symptoms when compared to the placebo group. As of now, AN-PEP is not intended to replace a gluten-free diet, but rather to reduce symptoms associated with consuming trace amounts of gluten. 

Gluten sequestration uses molecules with a high binding affinity for either gluten or gliadin, a protein that makes up gluten. When these molecules bind to their target protein, they render the protein unable to interact with the immune system. One such treatment uses Avian Immunoglobulin Y (AGY) derived from egg yolks. A study in mice showed that when given gliadin and AGY, less than 1% of the gliadin reached the animal’s gastrointestinal tract. This result, along with the low cost of AGY production and general safety of the substance, makes this treatment promising, although later-stage trial results have not been published. 

Tolerance strategies are especially appealing because they deal with the root problem, the pathological reaction to gluten. These treatments seek to either dampen the inflammatory reaction to gluten or redirect immune pathways away from their typical response toward one with less impact, while not broadly reducing immunity. This treatment would need to be administered intravenously, which may limit patient acceptance and make it less practical for long-term use. So far, multiple promising tolerization therapies are being tested, such as TAK-101 and KAN-101, which are still being studied for safety and efficacy in phase 2 trials. 

Despite scientists' best efforts, among the various treatments, none have proven to be effective long-term substitutes for a gluten-free diet. Although this might be disheartening news for people with celiac disease, for the scientific community, this means that there is more work to do to come up with creative solutions to the problem. 

Open Submission By Ava Carroll