Researchers in Oxford have found structures of immune cells in the gut that may be driving the response to gluten in people with coeliac disease and could provide a target for future therapies.
The team from the University of Oxford, supported by the NIHR Oxford Biomedical Research Centre (BRC), also found that many of these changes in the gut persisted despite treatment with a gluten-free diet, suggesting there may be an immune ‘scar’ in the gut, which could explain why some patients experience ongoing symptoms.
Coeliac disease is a common condition affecting around one in 100 people. Symptoms are triggered by exposure to gluten in the diet. Gluten is found in foods containing wheat, barley and rye.
However, we do not know why some people develop the disease and others do not, nor how the changes seen in the gut take place. Although symptoms improve on a gluten-free diet, this does not represent a cure.
In this study, published in Nature Immunology, the researchers from the University’s Translational Gastroenterology and Liver Unit (TGLU), MRC Weatherall Institute of Molecular Medicine (MRC-WIMM) and Centre for Human Genetics used gene sequencing methods called single cell and spatial transcriptomics to study how different cell types in the gut lining changed in adults and children with coeliac disease.
These methods examine which genes are being expressed in every single cell in gut samples, and where in the gut lining these cells and genes are found.
This research showed that in coeliac disease, groups of different immune cells come together into organised structures in the gut lining. These structures may contain the key immune cells that recognise gluten and may act as the ‘control centre’ driving all the changes that we see in coeliac disease and as local ‘factories’ for the immune response.
These changes include many impacts on the epithelial cells that line the gut, which are responsible for absorbing nutrients, vitamins and minerals. The gut also accumulates ‘killer’ T cells, which are responsible for much of the damage seen.
Dr Michael FitzPatrick, consultant gastroenterologist and immunology researcher at the Nuffield Department of Medicine’s Experimental Medicine Division, co-led the study. He said: “While the gluten-free diet is the mainstay of treatment in coeliac disease, it is not effective or possible in everyone.
“Our study, which could not have happened without the generous participation of our patients and study participants, both adults and children, sheds light on how different types of immune cells communicate and interact in coeliac disease, and how they may drive the problems with absorption and symptoms patients face. New treatments could target the signalling pathways between these immune cells to short-circuit the inflammation in the gut.”
A surprising finding the researchers found was that many of these gut changes persisted despite treatment with a gluten-free diet. This may represent an immune ‘scar’ in the gut, which could be the cause of ongoing symptoms in some patients, and why symptoms can come back so quickly with inadvertent gluten exposure.
Agne Antanaviciute, an MRC-WIMM Computational Biologist who co-led the study, added: “Many people living with coeliac disease have problems with ongoing symptoms despite their best efforts at the gluten-free diet. This immune ‘scar’ in the gut lining that we have described could be contributing to their ongoing symptoms, and we hope that our study findings could lead to new treatments for our patients.
“These findings show in detail how the different components of the gut respond together in coeliac disease – and offers new targets for therapy, as well as potentially a cure.
As well as the NIHR Oxford BRC, this research received funding from Coeliac UK, Beyond Celiac, Wellcome and Breakthrough T1D.