Tag: coeliac disease

Categories : GastrointestinalTags :

Promising Molecule for Coeliac Targets Gluten in the Stomach

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Photo by Mariana Kurnyk

A research project led by the Institute for Research in Nutrition and Food Safety (INSA) and the Faculty of Pharmacy and Food Sciences at the University of Barcelona, together with the Molecular Biology Institute of Barcelona (IBMB) of the CSIC (which stands for Consejo Superior de Investigaciones Científicas), has successfully designed and tested a gluten-degrading molecule that is a promising ally in the management of coeliac disease, an autoimmune disease whose symptoms are triggered by the consumption of gluten and other prolamins found in cereals. At present, there is a complete lack of treatment options beyond a diet free from gluten, which is difficult to maintain in Western societies where diets rely heavily on wheat products.

The major breakthrough is that the molecule is effective at very low concentrations and at a pH of 2 (the pH of the stomach) a condition that none of the molecules currently available or under development had previously achieved with efficiency. Although some of them are marketed as nutritional supplements, they are not an effective alternative to gluten-free diets.

The study has been published in the journal EMBO Molecular Medicine ahead of the International Day of Coeliac Disease on 16 May and is led by researchers Francisco J. Pérez-Cano (INSA-UB), and F. Xavier Gomis-Rüth (IBMB-CSIC). The co-first authors are Marina Girbal-González and Arturo Rodríguez-Banqueri (INSA-UB and IBMB-CSIC, respectively). Teams from the Institute for Food Science Research (CSIC-UAM), the University of Salzburg (Austria) and the Technical University of Munich (Germany) have also participated.

Counteracting the ‘trigger’ of coeliac disease

The trigger for coeliac disease are the prolamins, proteins found in most common cereals in our diet, such as wheat gluten. When these are digested in the stomach, they break down into smaller fragments (peptides). Some of these can be toxic, such as the gluten immunogenic peptides (GIPs), which can withstand the stomach’s gastric acids and reach the small intestine. Among these, one of the most immunogenic is the the ‘33-mer’, a fragment of the α-gliadin in wheat gluten that is highly immunogenic.

This poses a problem for people with coeliac disease, because once in the small intestine, the 33-mer and other GIPs bind particularly easily to a receptor of the immune system (the human leukocyte antigen, or HLA), triggering the inflammatory autoimmune response that causes the characteristic symptoms of the disease.

The results demonstrate that celiacase, a molecule stable in the stomach environment, could be an adjunctive therapeutic candidate to support a gluten-free diet.

Four years ago, the Proteolysis Group at IBMB-CSIC, led by F. Xavier Gomis-Rüth, described in an article in Nature Communications that nephrosin – a molecule found naturally in the digestive juices of the carnivorous plant Nepenthes ventrata – was capable of cleaving GIPs, building on results from the group of David Schriemer from the University of Alberta in Canada. In collaboration with the Autoimmunity, Immunonutrition and Tolerance Group at the UB’s Faculty of Pharmacy and Food Sciences, led by Professor Francisco José Pérez-Cano, they demonstrated that nephrosin can degrade the 33-mer peptide and other GIPs before they reach the intestine, thereby potentially preventing this autoimmune inflammatory response.

Designed using molecular engineering

In this study, the team has designed and tested a molecule based on nephrosin. Named celiacase, this new molecule exhibits its maximum activity at the gastric pH of the stomach, where, in synergy with the pepsin in our digestive system, it breaks down the GIPs in cereals and the gliadin in wheat before they pass into the duodenum.

“There are other proteases, generically termed glutenases, which break down gluten, but they are not fully active at pH 2 – the pH of the stomach – but rather at pH 7 – the pH of the duodenum – when the bolus has already left the stomach,” explains Gomis-Rüth. “Therefore, it is necessary to increase the doses to levels that make them unviable for therapeutic use.”

The team has tested the molecule in vivo using a mouse model developed by the University of Chicago, which is currently the model that most accurately replicates coeliac disease. The results show that celiacase is effective at very low doses, being able to mitigate the symptoms of the disease in gluten-fed mice, even at high gluten intake levels. “Intestinal atrophy, inflammation, the antibody response and dysbiosis – that is, the alteration in the composition of the microbiota – were reduced,” says Pérez-Cano. “Furthermore, immunoregulatory markers were restored to normal levels, as were microbial metabolic pathways.”

Another advantage of celiacase is that it is no longer active once it reaches the duodenum. “Once it has accomplished its function, there is no need for it to remain active, so that it does not interfere with other proteins in the body,” adds Gomis-Rüth.

The molecule and its potential applications have been patented, and the team is taking the first steps towards setting up a spin-off company and taking the development to more advanced stages.

This study has been partially funded by programmes run by the Ministry of Science and Innovation, the Government of Catalonia’s Agency for Management of University and Grants (AGAUR) AGAUR, the Catalan Coeliac Association, and the CSIC’s Conexión Trigo network.

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Source: University of Barcelona

Categories : GastrointestinalTags :

New Research May Help Doctors Identify Coeliac Disease Earlier in Kids with T1D

On By ModernMedia
Photo by cottonbro studio

Children diagnosed with type 1 diabetes (T1D) face more than just managing their blood sugar. They are also at a higher lifelong risk of developing coeliac disease. Because of this, regular screening is recommended to catch coeliac disease early in kids with T1D.

A new article published in Clinical Chemistry takes a closer look at how blood tests for coeliac disease can be used more effectively in this group of patients. In celiac disease, elevated TTG-IgA antibodies are often the first step in the diagnostic process. If blood levels of TTG-IgA are elevated, patients are typically sent for a biopsy to confirm coeliac disease. In kids with T1D, this can be a bit more complicated. In children with T1D, TTG-IgA antibody levels can fluctuate, and there hasn’t been a clear cutoff for when a biopsy is truly necessary.

Researchers studied nearly 600 children with T1D and found that using a cutoff of six times the normal limit gave the best balance of accuracy, which performed better than the older cutoff of 11 times the normal limit. The study also showed that kids who developed celiac disease soon after being diagnosed with T1D often had higher antibody levels right away, while those who developed celiac disease later had lower levels in the beginning. This highlights the importance of testing at the time of T1D diagnosis and continuing to monitor regularly, even if early test results aren’t extremely high.

“Our article looked at recent work investigating serologic assays’ efficacies in pediatric patients with type 1 diabetes. We found that recent data such as those seen in Muller et al.’s study (2025) suggest that lower transglutaminase elevations can portend coeliac disease in this population than previously thought, and the disease remains considerably prevalent among patients with T1d. As such it is crucial to actively evaluate for CeD in T1d patients, and the serologies provide an excellent tool for doing so,” said study author Dr Andrew M. Ford.

For families, the key takeaway is that regular screening matters, and doctors are working to fine-tune how these tests are used so children with both T1D and coeliac disease can be diagnosed as early and accurately as possible.

Source: Celiac Disease Foundation

Categories : Allergies Lab Tests and ImagingTags :

Gluten Free Diet Reduces Coeliac Symptoms – and ‘Good’ Gut Bacteria

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Photo by Mariana Kurnyk: https://www.pexels.com/photo/two-baked-breads-1756062/

A research team led by the University of Nottingham has used magnetic resonance imaging (MRI) to better understand the impact a gluten free diet has on people with coeliac disease, which could be the first step towards finding new ways of treating the condition.

The MARCO study – MAgnetic Resonance Imaging in COliac disease is published in Clinical Gastroenterology and Hepatology (CGH) (link connects to BioRxiv copy).

Coeliac disease is a chronic condition affecting around one person in every 100 in the general population. When people with coeliac disease eat gluten, which is found in pasta and bread, their immune system produces an abnormal reaction that inflames and damages the gut tissue and causes symptoms such as abdominal pain and bloating.

The only treatment is a life- long commitment to a gluten free diet, which helps recovery of the gut tissue but still leaves many patients with gastrointestinal symptoms.

Luca Marciani, Professor of Gastrointestinal Imaging at the University, led the study. He said: “Despite being a common chronic condition, we still don’t precisely know how coeliac disease affects the basic physiological functioning of the gut and how the gluten free diet treatment may further change this.

“We launched the MARCO study to try and address this issue, by using MRI along with gut microbiome analysis to give us new insights into how a gluten-free diet affects people with coeliac disease.”

The team recruited 36 people who had just been diagnosed with coeliac disease and 36 healthy volunteers to participate in the study. Images were taken of their guts with MRI, along with blood and stool samples. The patients then followed a gluten free diet for one year and came back to repeat the study. The healthy participants came back one year later too and repeated the study, but they did not follow any diet treatment.

The study found that the newly diagnosed patients with coeliac disease had more gut symptoms, more fluid in the small bowel and that the transit of food in the bowel was slower than in the healthy controls.

The microbiota (the ‘bugs’ living in the colon) of the patients showed higher levels of ‘bad bugs’ such as E.coli. After one year of a gluten free diet, gut symptoms, bowel water and gut transit improved in the patients, but without returning to normal values. But the gluten free diet also reduced some of the ‘good bugs’ in the microbiota, such as Bifidobacteria associated with reduced intake of starch and wheat nutrients, due to the different diet.

The patient study was conducted by Radiographer Dr Carolyn Costigan, from Nottingham University Hospitals, as part of her PhD studies at the University of Nottingham.

It was particularly interesting to see how the imaging results on gut function correlated with changes in the ‘bugs’ in the colon microbiota. The findings increase our understanding of gut function and physiology in coeliac disease and open the possibility of developing prebiotic treatments to reverse the negative impact of the gluten free diet on the microbiome.”

Luca Marciani, Professor of Gastrointestinal Imaging

Dr Frederick Warren from the Quadram Institute, which contributed to the research, said: “This study is the result of an exciting and innovative research collaboration bringing together medical imaging technology and gut microbiome analysis. We provide important insights which pave the way for future studies which may identify novel approaches to alleviate long-term symptoms in coeliac patients.”

Source: University of Nottingham