SCIENTISTS AT THE UNIVERSITY OF BARCELONA have engineered a molecule capable of breaking down gluten in the stomach before it triggers the autoimmune response that drives coeliac disease — a breakthrough that could transform how the condition is managed in patients who currently have no treatment options beyond a strict, lifelong gluten-free diet.
The Science
The Enzyme Discovery
What It Means for Patients
The research, published May 14, 2026 in EMBO Molecular Medicine, was led by teams at the Institute for Research in Nutrition and Food Safety (INSA) and the Faculty of Pharmacy and Food Sciences at the University of Barcelona, in partnership with the Molecular Biology Institute of Barcelona (IBMB) of the CSIC research council. The work was conducted in collaboration with teams from the Institute of Food Science Research in Madrid, the University of Salzburg, and the Technical University of Munich.
**The Problem with Gluten**
Coeliac disease affects roughly one in 100 people worldwide. The condition is triggered by prolamins — proteins found in wheat, barley, and rye — which, when digested in the stomach, break down into fragments called gluten immunogenic peptides (GIPs). Among the most dangerous of these is the 33-mer, a fragment of α-gliadin in wheat gluten that is highly immunogenic. The 33-mer survives the stomach’s gastric acids intact and travels to the small intestine, where it binds to a human leukocyte antigen (HLA) receptor, sparking the inflammatory autoimmune response that causes coeliac symptoms.
Current management relies entirely on eliminating gluten from the diet — a difficult undertaking in Western societies where wheat products are deeply embedded in daily food supplies.
**A Molecule Built from a Plant**
Four years ago, the Proteolysis Group at IBMB-CSIC, led by Research Professor F. Xavier Gomis-Rüth, described in Nature Communications that nephrosin — a molecule naturally present in the digestive juices of the carnivorous plant Nepenthes ventrata — was capable of cleaving gluten immunogenic peptides. The new study builds on that foundation.
In collaboration with the Autoimmunity, Immunonutrition and Tolerance Group at the University of Barcelona, led by Professor Francisco José Pérez-Cano, the team designed and tested an optimized molecule derived from nephrosin, naming it celiacase.
“What sets celiacase apart from other gluten-degrading molecules — some of which are marketed as nutritional supplements — is that it works at pH 2, the actual acidity of the stomach,” said Professor Gomis-Rüth. “Most other glutenases are only fully active at pH 7, the pH of the duodenum, long after the gluten fragments have already left the stomach. That is why previous attempts have required doses so high they become therapeutically unviable.”
**Efficacy at Low Doses**
The team tested celiacase in vivo using a mouse model developed by the University of Chicago — currently regarded as the most accurate experimental model of coeliac disease. Results showed the molecule was effective at very low doses, reducing intestinal atrophy, inflammation, antibody responses, and dysbiosis — the harmful alteration of gut microbiota — even at high gluten intake levels. Immunoregulatory markers and microbial metabolic pathways were restored to normal levels.
A further advantage of celiacase is its self-limiting behaviour: it becomes inactive once it reaches the duodenum, having completed its work in the stomach. This means it does not interfere with other proteins in the body after its therapeutic function is complete.
**From Bench to Bedside**
The molecule and its potential applications have been patented, and the research team is taking the first steps to establish a spin-off company to bring the development to more advanced stages. However, the scientists caution that human trials have not yet begun.
“This could become an adjunctive therapeutic candidate to support a gluten-free diet, not a replacement for it,” said Professor Pérez-Cano. “But for patients who face accidental exposure, or for whom strict dietary adherence remains nearly impossible, this represents a genuine new approach where none previously existed.”
The study was published ahead of the International Day of Coeliac Disease on May 16, 2026.
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