Dr Michael FitzPatrick, Consultant Gastroenterologist and Immunologist (pictured on the right)
“Whilst the gluten free diet is currently the only treatment for coeliac disease, it’s not effective for everyone. Many people living with coeliac disease have problems with ongoing symptoms despite following a strict gluten free diet. Our study sheds light on how different types of immune cells communicate and interact with one another in coeliac disease, and how they may drive gut damage and cause symptoms for patients. This immune ‘scar’ that we have described in the lining of the gut could be contributing to ongoing symptoms, and we hope that our study findings could lead to new treatments for patients with coeliac disease. New treatments could look to target the signalling pathways between immune cells which could stop inflammation in the gut, reducing symptoms.” said Dr Michael FitzPatrick who has been working on the project.
In people with coeliac disease, we know that gluten triggers an immune response. However, there is much we do not know, including why some people develop the disease and not others, and how the changes that can be seen in the gut actually take place. Although symptoms improve for most people who follow a strict gluten free diet, the diet is not a perfect solution and does not represent a “cure”. The gluten free diet is restrictive, and gluten free options are typically more expensive and less widely available than gluten containing equivalents. In addition to this, many people experience ongoing symptoms despite following a strict gluten free diet.
In this study, Dr Michael FitzPatrick and Dr Agne Antanaviciute at the University of Oxford used gene sequencing methods called single cell transcriptomics and spatial transcriptomics to study how different cell types in the lining of the gut change in both adults and children with coeliac disease. These special methods allowed them to examine the genes that are being expressed in every single cell in samples from the gut. The special methods also allowed them to look at where in the gut lining these cells and genes are found. In more simple terms, the methods they used allowed them to look at what instructions each individual cell is reading, how these instructions impact that individual cell and also how these instructions impact other cells (in the context of coeliac disease).
Dr Agne Antanaviciute, Computational Biologist (pictured above)
“This fantastic research could not be done without the generous and selfless participation of our patients and study participants here Oxford, and also the support of Coeliac UK”, said Dr FitzPatrick.
The research showed that in coeliac disease, different immune cells come together in groups to form organised structures in the lining of the gut. These structures may contain the key immune cells that recognise gluten and wrongly identify gluten as a threat to the body. The structures may act as “control centres” driving the immune response and the changes that are commonly seen in patients with coeliac disease. This includes an increase in special immune cells called T “killer” cells which are known to cause inflammation and gut damage, harming epithelial cells which line the gut and are responsible for absorbing nutrients, vitamins and minerals.
The researchers were surprised to find that many of these gut changes persisted despite patients following a strict a gluten free diet. This may represent an immune ‘scar’ in the gut, which could be the cause of ongoing symptoms in some people with coeliac disease and may also explain why symptoms come back so quickly when a person with coeliac disease accidentally consumes gluten.
The full paper is published in Nature Immunology, 6 May 2025:
“Immune–epithelial–stromal networks define the cellular ecosystem of the small intestine in celiac disease”, DOI: 10.1038/s41590-025-02146-2.
For more information on coeliac disease, and ongoing symptoms please visit here.
The work was carried out by Dr Michael FitzPatrick, Consultant Gastroenterologist and Researcher in Immunology, Dr Agne Antanaviciute, Computational Biologist and Professor Paul Klenerman, Professor of Gastroenterology.