Scientists have discovered how the gut lining affects coeliac disease
Gluten intolerance is the cause of debilitating pain and gut problems for hundreds of thousands of people, but the only solution to stop these symptoms is to completely cut gluten out of their diet.
But now, scientists hope that new therapies to treat celiac disease can be developed after a new study identified the exact role played by the gut lining in the body’s reaction to gluten.
The study, carried out by an international team that was led by researchers from McMaster University in Canada, used transgenic mice to identify the role played by the cells in the gut’s lining.
The discovery could help the one in 100 people in the UK who have coeliac disease, which is caused by an immune reaction to eating the protein called gluten.
Gluten can be found in foods containing wheat, barley or rye. When a person with coeliac disease or gluten intolerance consumes gluten, they may experience symptoms like diarrhoea, nausea and vomiting, bloating, abdominal pain, and fatigue.
Following a strict gluten-free diet is currently the only way to treat coeliac disease. However, Elena Verdu, a gastroenterologist at McMasters, told Science Alert: "This is difficult to do and experts agree that a gluten-free diet is insufficient."
How does coeliac disease develop?
Scientists already know that 90% of people diagnosed with coeliac disease carry a pair of genes that encode for a protein called HLA-DQ2.5, while most of the remaining 10% have a similar protein called HLA-DQ8.
These proteins are responsible for warning defensive tissues in the body about pieces of gluten peptide that are resistant to digestion, prompting white blood cells called T-cells - which are part of the immune system and help protect the body from infection - to find the errant gluten peptides.
However, people with these genes are at higher risk of developing autoimmune conditions like coeliac disease because the proteins are not accurate at distinguishing between real threats and similar-looking things in body.
In order for a person with these genes to develop coeliac disease, the pieces of gluten have to be carried across the gut wall by a transporting enzyme. This enzyme, which is released by cells in the intestinal wall, binds with the gluten peptide and makes it more recognisable.
The researchers wanted to figure out what role the cells in the intestinal wall play in the early stages of coeliac disease, and how this reaction functions within it.
What did the study entail?
The team examined the cells in the gut lining of people with treated and untreated coeliac disease, and in mice with the human genes for HLA-DQ2.5.
They then created an ‘organoid’, which is a functional living model of the gut. Using the intestinal cells from the mice, they then subjected the organoid to inflammatory triggers as well as predigested and whole forms of gluten.
This allowed them to observe that the cells in the gut lining are “key agents” in the body’s reaction to gluten, rather than simply being doomed to sustain damage caused by the immune system in its war against gluten.
The cells in the gut lining had a role in presenting the gluten antigens, which resulted in the activation of the immune system to get rid of gluten.
In the study, published in the journal Gastroenterology, the scientists wrote: "Therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in coeliac disease patients."
What have other studies found?
Another recent study by researchers at Stanford Medicine identified a previously unknown molecular link between gluten exposure and intestinal damage.
They found that a molecule called IL-7, which has been implicated in other autoimmune diseases, has elevated levels in tissue from people with active coeliac disease. The study also revealed that blocking the activity of IL-7 eliminated the immune reaction to gluten that damages the intestinal lining.
Calvin Kuo, professor of medicine and senior author of the study, said: "These results show that IL-7 is a previously unrecognised modulator of celiac disease.
"Although more research needs to be done, we believe that the organoids faithfully reflect what is happening in people with celiac disease and that there may be therapeutic opportunities for blocking IL-7 activity."
Nielsen Fernandez-Becker, professor of medicine and director of the Coeliac Disease Program at Stanford Health Care, added: "Celiac disease is kind of a chameleon. There are many things we don’t know. In particular, while we are pretty good at diagnosing the disease, we don’t have a great way of monitoring people.
"Biopsies are invasive, and not always helpful. And often people come to us already on a gluten-free diet, which makes diagnosis difficult and may mean we have to ask them to eat gluten to figure out if they really have celiac disease."
Read more about gut health:
Why beans are so good for your gut health (Yahoo Life UK, 9-min read)
What your breath says about your gut health (Yahoo Life UK, 5-min read)
How to choose the right yoghurt to support gut health (Yahoo Life UK, 4-min read)
