Project Title:  Improving the diagnosis and management of gluten ataxia

Professor Marios Hadjivassiliou is an NHS Consultant Neurologist whose primary research focus is on the neurological manifestations of gluten related diseases. Part of his research resulted in defining gluten ataxia and eventually led to developing a diagnostic test for the condition. He is also the Director of the Sheffield Ataxia Centre, where he cares for over 3000 patients with forms of ataxia.

Ataxia is a term for a group of conditions that affect balance, speech, and coordination. Over the last 25 years, research at the Sheffield Teaching Hospitals NHS Trust has identified a cohort of patients whose unexplained ataxia is due to gluten sensitivity (gluten ataxia).

Professor Hadjivassiliou explains “Gluten ataxia is a serious autoimmune condition where gluten ingestion causes damage to the cerebellum; the part of the brain which coordinates balance and speech. It can occur with coeliac disease or independently, and the only treatment is a strict gluten free diet for life. Early diagnosis is crucial to prevent permanent, long term damage and functional issues with speech, balance and coordination.”

Ongoing research at the Sheffield Institute of Gluten Related Disorders has led to the development of a new diagnostic blood test using a previously defined marker of gluten ataxia, transglutaminase 6 (TG6) antibodies. This is used over and above antigliadin antibodies that are also of diagnostic use in gluten ataxia. This blood test has been made readily available under the NHS in Sheffield, but is not yet available at other laboratories in the UK. Routine blood tests for coeliac disease are typically offered, but these lack sensitivity for gluten ataxia, meaning the majority of cases may go unrecognised. This project aimed to provide evidence for the wider use of the diagnostic test by demonstrating its value in identifying patients with gluten ataxia.

Jointly funded by Coeliac UK, Ataxia UK and Sheffield Hospitals Charity, the project was a collaborative study supported by consultant neurologists from other ataxia centres across the UK (London, Oxford and Manchester). Patients with unexplained forms of idiopathic sporadic ataxia (ISA), were recruited to investigate whether a proportion of these cases could be gluten ataxia. Previous research has shown that around 40% of ataxias where no other cause is found could actually be gluten ataxia.

A total of 103 patients from across the UK were referred to Professor Hajivassiliou’s team at the Sheffield Ataxia Centre for testing as part of this project. These were patients without a diagnosis of the cause of their ataxia.

Preliminary results have shown that out of 103 patients, 57 were confirmed to have no cause of their ataxia after full investigation. Among these cases, a positive TG6 and/or antigliadin antibody was found in 79% of patients. After diagnosis, patients were offered brain imaging, followed by referral to dietetic services for advice regarding the gluten free diet. It has already been shown that patients with gluten ataxia improve on a gluten free diet. By demonstrating the value of this diagnostic approach there will be a push for wider adoption of these tests, enabling more people to receive an accurate diagnosis and access treatment through a strict gluten free diet.

The study also provided insights into how gluten ataxia affects the brain. The team examined brain tissue and compared it to healthy and ataxia control tissue. There were distinct differences between these groups with gluten ataxia tissue showing evidence of inflammation and altered cellular processes responsible for breaking down proteins and producing energy. By improving our understanding of the biological changes that occur in gluten ataxia, this research could help identify new targets for treatment and support the development of more effective therapies in the future.

Professor Hadjivassiliou and his team are now focused on publishing these findings and working towards making the diagnostic test more widely available across immunology laboratories in the UK. A collaborative approach involving Coeliac UK and Ataxia UK has been proposed to support implementation and raise awareness of the value of diagnosing gluten ataxia. The research team is also continuing to investigate the role of TG6 to further understand the mechanisms of this disease.

Project Title: Psychological support for children and young people with coeliac disease

Dr Rose-Marie Satherley is a lecturer in clinical psychology at the University of Surrey. She has previously designed psychoeducation,screening tools and integrated healthcare interventions aimed at young people to support their health and manage disordered eating behaviours.

Following a rigorous peer and lay review process, we awarded funding to Dr Satherley and her team to develop psychological tools to support families of children and young people with coeliac disease. Although awareness of coeliac disease is increasing, many children and young people still struggle with the psychological and social impact of coeliac disease. The National Institute for Health and Care Excellence (NICE) guidelines ensure that families are given information about the gluten free diet but there are currently no tools or resources available to support their psychological wellbeing and adjustment to the diet.

Dr Satherley explains: “Life is full of ups and downs, especially when a gluten free diet is involved. Children experience coeliac disease in different ways, no two children are the same, but every child can find useful tools to help them follow a gluten free diet and live well with coeliac disease. These “tools” include the child’s experiences, their medical team, friends, family, and a range of psychological tools. This research will work with children and their families to find the best psychological tools that can support gluten free diet management and wellbeing at the same time.”

For the first stage of the project, the research team adapted psychological resources that had previously been developed to support children with other gut disorders like IBS and children with food allergies. They developed a self help eBook for families to use as a tool to manage coeliac disease together. The resource itself consisted of detailed but accessible information about the condition and emphasised the importance of following a strict gluten free diet. It focused on 4 key areas:

• Family attitudes towards the gluten free diet
• Addressing biased social standards or ‘norms’
• Understanding behaviour control
• Coping skills

Within these areas the resource provided strategies for positive social interactions related to gluten free foods and also provided families with knowledge to anticipate and manage challenges, including when eating outside the home. Finally, the resource provided families with quizzes, videos, worksheets and family activities to foster the development and maintenance of effective skills to manage day to day life and emotions, recognising the link between feelings and behaviours.

The intervention was evaluated through a pilot and feasibility randomised controlled trial. Families who volunteered to take part in the trial were randomly assigned to one of two groups. Some families were invited to use and provide feedback on the resource and some families were simply asked to report on how they felt they were coping with coeliac disease without any support and no access to the self help eBook. Members of Coeliac UK were able to express interest in taking part and the recruitment target was surpassed in under 24 hours which meant the research team could involve double the number of families than they had originally anticipated. This indicated a strong interest for a supportive resource to help families manage coeliac disease. Analysis of the feedback from families identified that the eBook was valued by families and integrated into everyday family life. It was able to support the management of the gluten free diet and dietary adherence. The research team identified areas for improvement such as increasing the time families spent actually engaging with the eBook to allow families to gain as much benefit as possible and peer support.

In 2024 the findings from the study were presented at the International Coeliac Disease Symposium in Sheffield, the British Society of Paediatric Gastroenterology and Hepatology meeting in Bristol and in 2025 in two publications. All families involved in the study were provided with a physical copy of the eBook to keep.

Building on the success of the project, the research team are planning to carry out a large scale study where the resource will be adapted to incorporate feedback and then offered to a much larger number of families across the UK. The new intervention will involve an online support group for families and has initiated collaborations within the NHS which will help to further develop the work. It’s hoped that in the future, a suitable resource will be available to all families managing coeliac disease.

Every Autumn we invite postgraduate students based in the UK to apply for up to £5000 worth of funding and our support to carry out a 12 month research project related to coeliac disease as part of their studies or professional development.

We are delighted to share the outcomes of the projects we awarded in December 2023.

The development and application of an online group cognitive behavioural therapy (CBT) based psychological intervention to support adults with CD

Imogen Hughes, University of Surrey

The primary issue that this research wanted to address was the lack of tailored mental health interventions available for people with coeliac disease. Existing evidence suggests that cognitive behavioural therapy (CBT) is successful in improving the mental wellbeing of people with lifelong conditions like irritable bowel syndrome (IBS) or arthritis, however there is limited evidence around whether it can also improve the mental wellbeing of people with coeliac disease. Therefore, this project aimed to develop an online CBT mental health intervention for adults with coeliac disease. It then evaluated the intervention via feedback from participants to see if it was able to improve mental wellbeing and quality of life.

The intervention was aimed at adults who had been diagnosed with coeliac disease within the last 2 years as during this period, individuals are making big lifestyle adjustments to promote gut healing.The project was extremely successful in recruiting adults with coeliac disease to take part in the CBT intervention, suggesting a high level of need for the type of support being offered.

Quantitative data showed statistically significant improvements in all areas by the time participants had completed involvement with the intervention. The study tracked measures relating to anxiety, depression and quality of life. Qualitative data feedback showed that participants felt validated and supported by the intervention and felt it was empowering as it provided practical strategies to manage coeliac disease and talk to others about their needs.

Following on from feedback the initial intervention is going to be further improved before being tested with a larger group. Participants felt that more sessions would be useful and also recommended that it be made available for people who had been diagnosed longer than 2 years ago. It’s hoped that by gathering further evidence the intervention will be able to be recommended as a tool for people with coeliac disease.

Exploring the views of primary and secondary care physicians on the no-biopsy diagnosis of coeliac disease in adults: a qualitative interview study

Mohamed Shiha, University of Sheffield

The purpose of this work was to collect and share how healthcare professionals feel about a no biopsy approach to diagnosing coeliac disease to identify barriers and challenges. By identifying these, recommendations could be made to ensure that the no biopsy approach to diagnosis is offered to eligible patients.

The current gold standard method for diagnosing coeliac disease involves a blood test and biopsy. During the pandemic, interim guidance from the National Institute of Care Excellence (NICE) meant that some people could have a diagnosis of coeliac disease without the need for a biopsy and many areas of the UK continue to operate under this guidance. This project consisted of interviews with gastroenterologists and general practitioners (GP) in the UK with varying levels of experience, to collect their thoughts on diagnosing people with coeliac disease without an endoscopy and biopsy.

From the interviews, it was found that both groups were supportive of a no biopsy approach to diagnosis. This was due to advantages such as improved patient satisfaction, shorter waiting times before patients can begin treatment and reduced pressures on NHS services. However, it was also suggested that clear guidelines are really important. The healthcare professionals mentioned concerns such as false positive results and issues relating to the management of those with ongoing symptoms who hadn’t been diagnosed with a biopsy. There were also concerns relating to other conditions that might be identified or ruled out by biopsy.

The findings of this study have been published in an open access, peer reviewed journal and were also presented at the United European Gastroenterology Conference in Vienna in October 2024 which was attended by over 11,500 people.

Project Title: An artificial intelligence solution for diagnosis and assessment of small intestinal biopsies in suspected or known coeliac disease

Professor Elizabeth Soilleux, is an academic clinical pathologist at the University of Cambridge and honorary consultant at Addenbrooke’s hospital and this project brought together a multidisciplinary team of pathologists and mathematicians from the University of Cambridge and the University of Edinburgh.

This study aimed to use biopsy images of confirmed coeliac disease and biopsy images of ‘normal’ small intestines to develop an artificial intelligence algorithm that could accurately distinguish biopsy images from a person with coeliac disease from biopsy images from people without coeliac disease.

Currently, if a person is suspected to have coeliac disease, a doctor will request a blood test to look for the antibodies associated with the condition.If the blood test is positive, the diagnosis may be confirmed either by a second blood test or by an endoscopy and biopsy. This is where a small tube with a camera on the end is passed through the mouth into the small intestine and pieces of tissue lining the gut are removed for further analysis. A trained pathologist looks at these tissue samples under a microscope to look for signs of damage associated with coeliac disease. Unfortunately, due to a shortage of specialist pathologists in the UK NHS, this process can sometimes take too long. Not only this, but it’s though that there could be a difference of opinions of up to 25%between trained expert pathologists.

In 2019, along with Innovate UK, we awarded £175k of funding to a project aiming to develop an artificial intelligence software system that could look at these small intestine biopsies and identify if the person it came from has coeliac disease.

Artificial intelligence can be described as a computer system that uses information to learn and to recognise patterns independently, without human interference. Artificial intelligence means the reproduction of human intelligence in computer automated machines. Through complex programming, the machine learns how to process information and make decisions based on the information received, similar to the way humans do.

The project was a success, and the funding facilitated the development of a software system that is able to identify coeliac disease biopsies with an accuracy of 95%, which is a greater accuracy than that of trained pathologists (85%). The National Institute for Health and Care Research (NIHR) has awarded the team a further £620k worth of funding to continue this groundbreaking research. That means that the return on investment is about £3.60 for every £1 originally awarded by Coeliac UK and Innovate UK. The research team intend to use the follow on funding to improve the intelligence of the system so that it’s able to identify coeliac disease biopsies amongst a variety of other gastrointestinal conditions. They also plan to refine the software to hopefully improve accuracy further. They will then seek to validate the system in the hope that one day, it might be ready for clinical use, to allow the majority of people to be diagnosed with coeliac disease much quicker than if they had to wait for a pathologist to be available. Uncertain cases would still need to be looked at by an expert pathologist.

The original project was jointly funded by a grant from Coeliac UK and Innovate UK. Innovate UK is an organisation within the UK government’s national research and funding agency that invests in science and research.

Project Title: Development and validation of a minimally invasive comprehensive diagnostic coeliac disease test

Professor Elizabeth Soilleux, is an academic clinical pathologist at the University of Cambridge and honorary consultant at Addenbrooke’s hospital in Cambridge. Here, her team attempted to develop a laboratory based method of diagnosing coeliac disease without the need for the patient to consume gluten or to have an endoscopy and biopsy.

In coeliac disease, lymphocytes (a type of white blood cell) attack tissues in the gut.The lymphocytes involved in coeliac disease have previously been shown to have a unique section of DNA specific to coeliac disease. This project aimed to develop a diagnostic test based on reading this section of DNA in patients.It was hypothesised that reading these sequences could identify people with coeliac disease.

Professor Soilleux’s team looked at DNA in both blood samples and tissue from the gut (duodenal biopsies) obtained from the Cambridge University Hospitals Human Tissue Research Biobank. They compared samples from people diagnosed with coeliac disease and people who did not have a diagnosis of coeliac disease.

The project successfully created a cheaper and simpler method of finding lymphocyte DNA sequences, but unfortunately, this method did not find enough lymphocyte DNA sequences in each sample to be a suitable method of providing an accurate diagnosis.

The research has created a greater understanding of what needs to be obtained from a patient sample for an accurate diagnosis of coeliac disease using this method. Progress was made on the methods for analysing lymphocyte DNA sequences. When a more suitable laboratory method for obtaining these DNA sequences from patient samples is identified, a new diagnostic test could be developed that does not require gluten consumption.

The initial funding has also primed further funding and the researchers of this project have been awarded a £5 million grant as this new method of analysing lymphocyte DNA shows significant promise in exploring lymphocytes in cancer research.

This grant was jointly funded by Coeliac UK and Innovate UK. Innovate UK is an organisation within the UK government’s national research and funding agency that invests in science and research.

Project Title: Protein ingredients from UK crops as a source of gluten like functionality 

Dr Lydia Campbell, the founder of Nandi Proteins Ltd (a protein technology organisation) and Associate Professor in the school of Engineering and Physical Science at Heriot-Watt University collaborated with Agrii a major UK agronomy company and AB Mauri a distributor of bakery ingredients in an attempt to develop a novel ingredient that could be used in gluten free baking to improve the quality of the end product.

This work was important as new ingredients that can be used in the development of gluten free products, to improve overall quality, sensory properties, nutritional content or reduce the cost to the consumer, are welcomed by the gluten free community.

In this project, different protein concentrates were developed from sustainable crops and tested as ingredients in gluten free bread and muffin formulations. Trial batches were produced and compared to the gluten free formulations currently being used.Only one option showed potential; a protein concentrate from faba beans. It showed promise as a cost-effective ingredient to replace egg whites in gluten free baking and appeared to improve the quality of gluten free bread. The taste, texture, volume and appearance of the bread were assessed.

The bread on the left was made using a standard gluten free mix and the bread on the right was made using a gluten free mix where faba bean concentrate replaced egg white. As you can see, the breads had similar crumb textures, similar sizes and similar volumes. Initial feedback suggested that the bread using the faba bean protein tasted better than the standard gluten free bread mix.

The muffin on the left was made using a standard gluten free muffin mix and the muffin on the right was made using faba bean concentrate in place of egg white. As you can see, the muffins had similar crumb textures but the muffin containing the faba bean protein had more volume, indicating better performance. As with the bread, initial feedback suggested that the taste of the muffin was better when made with faba bean concentrate, compared to a standard gluten free muffin mix.

This research suggests that the quality and variety of gluten free products can be further improved to create better options for those who are unable to eat gluten containing foods. Research is ongoing to determine how the faba bean protein concentrate can be produced on a commercial scale to provide a sustainable source to the food industry, as an ingredient for consideration in new product development.

It is unlikely research would have gone ahead without the grant from Coeliac UK and Innovate UK (an organisation within the UK government’s national research and funding agency that invests in science and research). Not only has a new ingredient been developed for use in gluten free products but the research brought together a team who may not have otherwise collaborated on such a project e.g. crop grower, protein scientists, academics, ingredient specialists and a gluten free manufacturer. The funding has significantly facilitated and accelerated developments.

Project Title: Using software to improve the long-term management of people affected by coeliac disease 

Chris Kennelly, founder and CEO of Cievert Ltd., a digital health organisation which was established in 2011 to develop clinical administration software specifically for the UK, designing web-based, patient, referral, management and engagement systems across a number of disciplines. Cievert’s specialist oncology tertiary referral software has been adopted across the UK, and it was the first company to develop and launch vaccine booking software during the pandemic by adapting its flu vaccine booking system. For this project, Chris Kennelly partnered with the Sheffield gastroenterology department.

The National Institute for Health and Care Excellence (NICE) guidelines recommend that patients with coeliac disease are offered an annual review.In this project, researchers adapted Cievert’s existing cancer patient management software to support people diagnosed with coeliac disease.

They then invited adults to test and evaluate the system.Adults with a diagnosis of coeliac disease were prompted via email to answer an online questionnaire on three separate occasions during a 12 month period. The questions were based on guidelines from the British Society of Gastroenterology (BSG)and NICE. If a patient response indicated an issue or that they may require support, the answer was flagged to specialist clinicians in Sheffield for further inspection. If necessary, the clinician would then contact the patient.

Unfortunately, the COVID-19 pandemic impacted the way this work was carried out and there were fewer participants than the study had originally planned to recruit. Despite the challenges, the software was successfully adapted to be suitable for use with patients with coeliac disease and feedback from participants suggest that the software could be used to safely and remotely support patients with coeliac disease successfully assessing dietary adherence and monitoring ongoing symptoms.The software has the potential to ensure patients who require medical care are given the correct support in a timely manner.

For this software to be rolled out more widely, and made accessible to NHS patients, the evaluation study would need to be replicated with a larger number of patients and in different areas around the UK. There are also many individual and organisation barriers that must be overcome.

The development and testing of the application for coeliac disease would not have been possible without the funding, provided jointly by Coeliac UK and Innovate UK. Innovate UK is an organisation within the UK government’s national research and funding agency that invests in science and research.

Project Title: Contemporary epidemiology of coeliac disease, dermatitis herpetiformis, Crohn’s disease and ulcerative colitis in the United Kingdom 

Previously funded epidemiology research has shown that only 30% of the 1 in 100 who have coeliac disease have been diagnosed which means there are currently nearly half a million people who have the condition but don’t yet know. The aim of this research project was to provide the most up to date information on the diagnosis of coeliac disease, dermatitis herpetiformis, Crohn’s disease and ulcerative colitis in the UK.

Using the Clinical Practice Research Datalink (CPRD), which collects anonymised general practice healthcare records, the researchers determined how many people are living with each condition and how many are newly diagnosed each year. The number of people diagnosed was described by age, gender, ethnicity, socioeconomic status and geographical region.

The researchers looked at how many people were previously diagnosed or treated for irritable bowel syndrome (IBS) before being diagnosed with coeliac disease or inflammatory bowel disease.

Epidemiology studies are important for understanding the possible causes of the diseases and why they are more common in some people or geographical areas than others. This can be used to help identify people or areas that need targeting for diagnostic investigation or increased awareness of symptoms.

Project title: Understand why some patients with coeliac disease don’t feel better despite being on a gluten free diet 

Professor Ramesh Arasaradnam is a Consultant Gastroenterologist at University Hospitals Coventry & Warwickshire and clinical academic at the universities of Coventry, Leicester and Warwickshire. His research interests focus on inflammatory conditions within the gastrointestinal tract and the application of non invasive technology for early disease diagnosis.

What was the main issue your research was seeking to address?

We aimed to study the ‘chemical signature’ of cells and gut bacteria in people newly diagnosed with coeliac disease and observe any subsequent changes in these six months after people have been established on a gluten free diet.

Our hypothesis was that changes in the gut bacteria may explain, at least in part, why some patients with coeliac disease do not feel better despite following a gluten free diet.

What were you hoping to find out through this research?

We were hoping to identify ‘chemical signatures’ in people newly diagnosed with coeliac disease, which might then alter/normalise after being established on a gluten free diet. We were specifically hoping to find these changes using non-invasive methods such as a urine test. Secondly, we were hoping to show that this change in chemical signature mirrors the change in gut bacteria pattern before and after commencing a gluten free diet.

How successful was the project in achieving this?

We demonstrated that with a urine sample we can detect differences in the chemical signature pattern before and after starting a gluten free diet within the same individual. This is important as we have a simple test (urine) that can potentially track a patient with coeliac disease throughout the course of their condition.We also identified four key chemicals that were present in people with coeliac disease that were not present in the control group(people without the condition). However, the significance of these chemicals and what it means in terms of cell activity for people with coeliac disease, needs to be studied further.

We also showed that the gut bacteria in those who were established on a gluten free diet altered to become a more ‘normal’ pattern.

How will this project benefit patients?

The learning from better understanding the chemical signatures and gut bacteria in people who respond well on a gluten free diet could potentially be applied to modify gut bacteria in patients that do not achieve full symptom response or experience symptom relapse on a gluten free diet.These findings are novel and set the scene for further detailed studies on understanding what happens to those with coeliac disease, who then commence a gluten free diet and respond at the cellular level, as well as what happens to their gut bacteria.

What are the next stages for this work?

There are several avenues that we can pursue:

• Validate our findings by looking at the changes in the chemical signatures, before and after a diagnosis of coeliac disease, in another group of people with the condition
• Further determine the importance of the four chemicals in urine that we have identified in people with coeliac disease
• Explore the gut bacteria further, especially their metabolic function and if it’s linked to the chemicals identified
• Eventually as a treatment option, to look at gut bacteria supplementation as we gain understanding of what a ‘normal’ or healthy bacterial population should look like

Project Title: Investigating the relationship between the immune system and coeliac disease; a greater understanding towards possible prevention strategies or new target areas for personal treatment 

Professor Frits Koning is an immunologist with a special interest in gastrointestinal diseases.He was the director of the Dutch Coeliac Disease Consortium, from 2004 to 2014. In this consortium immunologists, medical doctors, geneticists and food experts have joined forces to understand the complex interactions leading to coeliac disease.

What was the main issue you wanted to address?

Put simply, the research aimed to understand how the two arms of the immune system are involved in coeliac disease. To explain in more detail, the immune system is complex and can make both adaptive and innate responses. Adaptive responses lead to immunological memory, which means that once a response has been made by a person’s immune system, they are then immune and respond stronger the next time they are exposed to the same pathogen (which can be bacteria or a virus that can cause illness). Of course, in people with coeliac disease the immune system mistakenly treats gluten as a pathogen, so the only treatment is a lifelong gluten free diet, to avoid reactivation of the memory response outlined above. The innate immune system is a first line of defence, and it is still unclear if and how this is involved in coeliac disease. Improving our understanding of the immune system and gluten could potentially help people with coeliac disease in several ways: from finding targets for alternative treatments to even preventing the onset of the condition in the first place.

What are the key things you learned from this project?

Thanks to a new technique we were able to study the immune system in an entirely different way. We were hoping that this would reveal which components of the immune system derail when coeliac disease develops. The result is that we have obtained strong evidence that multiple components of the immune system are involved, from both the adaptive and innate parts.

The most important coeliac disease-associated changes in the immune system are found in intestinal biopsies (where some tissue from the small intestine is examined). These changes are found in both the adaptive and innate parts of the immune system. We also noticed changes to the immune system within patients’ blood samples and have gained new insight into the cell type involved in the development of refractory coeliac disease.

How will this project benefit people with coeliac disease?

The fact that we have found coeliac disease associated changes in blood samples could lead to the improvement of diagnosis procedures. And in the long run, a better understanding of how the immune system responds, can help us find out why coeliac disease patients respond to gluten in the way they do. This may even lead to finding out how to prevent this reaction in the future.

Project Title: Can a blood test identify people who cannot tolerate oats? 

Dr Jason Tye-Din is a medical graduate of the University of Melbourne, Australia and completed gastroenterology training at the Royal Melbourne Hospital. He has practiced medicine since 1996, and for the last 15 years has combined coeliac disease research with patient care. His PhD examined immune responses to gluten in coeliac disease which led to the development of an immunotherapy now in clinical trials.

What was the main issue your research was seeking to address?

Oats contain avenin, a protein similar to gluten which is found in wheat, barley and rye. A small number of people with coeliac disease may also be intolerant to oats however, it is difficult to identify those people in advance. In a previous study we have shown 1 in 12 (8%) of people with coeliac disease had an immune response after they consumed oats, producing oat specific T cells (a type of immune cell) detectable in their bloodstream. The aim of this research project was to validate the role of a blood test to identify patients “at risk” of oat toxicity.

How successful was the project in achieving this?

The study has not yet completed the primary aim, because in order to verify the role of a blood test, a significant number of people who have a “positive” immune result is needed to correlate with clinical data (biopsy samples). However,a significant number of people with a “positive” immune response have not been found so the project has been revised to allow us to study the differences between avenin proteins in different varieties of oats. We reasoned that a higher dose of oats is more likely to stimulate an immune response. To achieve this goal, we developed a method to extract pure avenin from oats.

What are the key things that were learnt as a result of this project?

Immune responses to oats do occur in some people with coeliac disease but are relatively uncommon even when 100g of oats is consumed. Gut damage is seen in a subset of people with coeliac disease after they consume gluten free oats for three months. However, it is difficult to determine whether the changes are definitely caused by oats or other things such as accidental gluten exposure. The amount of avenin protein present in different varieties of oats is variable. We developed a method to extract pure avenin protein from oats suitable for human consumption. This will allow us to undertake more studies to assess oat toxicity and validate the immune blood test.

How will this project benefit patients?

Once successfully completed, the project will establish the role for a simple blood test to identify those at risk of oat toxicity.

How has the funding from Coeliac UK made a difference?

The funding from Coeliac UK has been instrumental in allowing us to carry out the immune studies to assess responses after oats ingestion and support some of the protein chemistry work that helped define the avenin proteins in oats.

Project Title: Patients’ and healthcare professionals’ perspectives on the reasons for long term follow up of coeliac disease and the manner it should take 

Dr Manpreet Bains is an Assistant Professor in qualitative and mixed methods health research in the division of epidemiology and public health, University of Nottingham. Manpreet is a researcher who has forged a respected research career, particularly in qualitative methods spanning a broad variety of topics in public health and health services research.

What was the main issue your research was seeking to address?

The National Institute for Health and Care Excellence (NICE) guidelines recommend that people with coeliac disease should be followed up annually by a relevant physician or dietitian in secondary or primary care. However, not only is the evidence that has guided these recommendations limited but the views and experiences of the patients, and healthcare professionals involved in its management have not been considered.

What were you hoping to find out through this research?

First, we wanted to understand the patients’ and healthcare professionals’ understanding and importance of follow up and current practice.Finally,we wanted both groups’ views on the best way to manage long term follow up.

How successful was the project in achieving this?

We interviewed a broad range of individuals with coeliac disease (n = 50), including those who attend follow up and those who do not. We also interviewed healthcare professionals (n = 43) from general practice, dietetics and gastroenterology.

The key findings from patients included:

• Patients reported initial management was difficult due to confusion and lack of support with this having both physical and psychological implications.
• Some individuals reported feeling supported by family and friends, whilst others felt isolated and found it difficult to socialise.
• Most agreed that an annual review with a consistent healthcare professional with the appropriate knowledge would be sufficient form of follow up, along with additional services to deal with any immediate issues.

Key findings from healthcare professional interviews:

• Some healthcare professionals felt there was a lack of evidence to suggest continued follow up, whilst others thought it was essential for ensuring compliance to the gluten free diet and prevention for further complications.
• Many felt there was little benefit in chasing those who did not wish to attend, stressing that an element of patient responsibility and engagement was an important factor in the successful management of coeliac disease.
• Current follow up practice indicated a raft of variations in treatment across the HCPs ranging from ongoing regular appointments and clinics to being discharged relatively soon after diagnosis.

Both groups agreed that the importance and purpose of a long term follow up should be stressed more clearly, and how to implement this.

How will this project benefit patients?

We have been able to identify both patients’ and healthcare professionals’ views on follow up. We have shown that practice is varied and therefore patients are receiving differing levels of treatments. Both groups share similar views on certain topics but some differences were found, suggesting that there would be some benefit in outlining clearly what is expected from both groups in terms of the follow up process.

How has the funding from Coeliac UK made a difference?

The funding has been pivotal in helping to delve into the area of long term follow up. Our research is the first that has explored both patient and HCP views on long term follow up; particularly views on current practice and the most optimal way of moving this aspect of care forward.

What are the next stages for this work?

Our work has identified various models for how follow up could be delivered; but we need to be able to obtain views on these in a larger sample of patients and healthcare professionals to take the work forward. We will use our findings to inform the development of these scenarios. For instance, participants will be asked to choose from who they would prefer to see gastroenterologist/GP, setting (hospital located 30 mins away/surgery a short walk) etc. By running this choice experiment in a larger group of people we will be able to come up with a list of potential follow up models that could be tested in a larger trial.

Project Title: A study to compare group versus individual dietetic intervention in patients with newly diagnosed coeliac disease

Nick Trott is a Gastroenterology Dietitian at the Royal Hallamshire Hospital, Sheffield covering the coeliac clinic. His clinical interests include coeliac disease, gluten ataxia, non coeliac wheat sensitivity, and the low FODMAP approach for disorders of the gut brain interaction. Nick was awarded the ‘Coeliac Professional of the Year’ by Complete Nutrition in 2017. Nick was a key member of this research project’s team, alongside Professor David Sanders, comparing individual vs group dietetic appointments. Nick has presented on this topic at Coeliac UK’s Research Conference.

National guidelines recommend that patients newly diagnosed with coeliac disease should receive information and support on the gluten free diet from a healthcare professional with specialist knowledge of coeliac disease. A dietitian with expertise in coeliac disease is best placed to provide this support, but we know that people can face long waiting times for their first appointment with a dietitian.

Why did we fund this research?

The use of group clinics in coeliac disease has the potential to improve access to dietetic services and reduce waiting times – it is a model that is already working in other health conditions. Group clinics for coeliac disease are already running in some parts of the UK but there has been limited published data to compare outcomes from group clinics with individual appointments.To fill the gap in the evidence, Coeliac UK funded researchers at the Royal Hallamshire Hospital, Sheffield to explore if group clinics are as effective as traditional individual appointments. The research has now been published in Clinical and Translation Gastroenterology.

How was the research conducted?

People newly diagnosed with coeliac disease were allocated to either a group clinic or an individual appointment. Some people needed a one-to-one appointment to receive more tailored advice, such as those with multiple conditions (e.g.having both diabetes and coeliac disease) and people with communication barriers. These individuals were excluded from the analysis.

Several outcomes were compared between the two groups. The researchers looked at nutritional status, antibody levels in blood and also asked participants to complete validated questionnaires to assess adherence to the gluten free diet, quality of life and anxiety and depression. These measures were taken before the first dietetic session and at follow up three months after the first appointment.

What did the researchers find?

The researchers found no significant differences between the groups for nutritional status, adherence to the gluten free diet or antibody levels in blood. On average, those attending the individual appointments had lower scores for anxiety than those in the group sessions, however both groups had scores below the threshold for probable anxiety or depression.

There are two other potential benefits of group clinics. Firstly, they allow people newly diagnosed with coeliac disease to meet other people who are in the same position providing another support network. Secondly, the research also found that group clinics were also associated with cost savings, achieving a 54% reduction in dietetic resources when compared with one-to-one appointments.

What are the next steps?

To share this research among dietitians and as a model of good practice that may be considered by other dietetic departments who are providing services to people with coeliac disease.

Project Title: Neurological manifestations in people with coeliac disease 

Professor Marios Hadjivassiliou is a Consultant Neurologist whose primary research focuses on the neurological manifestations of gluten related diseases. As well as being a founding member of the Sheffield Institute of Gluten Related Diseases (SIGReD), he is Director of the Sheffield Ataxia Centre and a member of our Health Advisory Council (HAC).

What was the main issue your research was seeking to address?

This research aimed to investigate cognitive deficits (i.e. concentration, attention, memory, etc.) in patients with newly diagnosed coeliac disease compared to patients who have been diagnosed with coeliac disease for more than five years, to establish if a strict gluten free diet can improve neurological issues.

What were you hoping to find out through this research?

Previous reports have suggested that people with coeliac disease may have cognitive deficits. Based on these and our own experience of patients with neurological symptoms we aimed to first establish if cognitive deficits are present in people with coeliac disease and secondly if sticking to a strict gluten free diet can improve cognitive deficits and influence cognitive functioning in the long term.

What are the key things that were learnt as a result of this project?

The study found that patients with newly diagnosed coeliac disease have some limited cognitive deficits when compared to healthy people without coeliac disease. Such cognitive deficits can become worse when patients who have been diagnosed with coeliac disease for more than five years do not stick to a strict gluten free diet. Patients who have been diagnosed for more than five years and who follow a strict gluten free diet seem to have better cognitive function.

How will this project benefit patients?

Patients with coeliac disease often experience neurological symptoms. By establishing the presence of cognitive deficits and demonstrating that a gluten free diet may be beneficial in improving cognitive function, we believe that the results will motivate people to maintain a strict gluten free diet strictly and also reassure people that any cognitive deficits they are experiencing may be reversible.

What are the next stages for this work?

Firstly, these findings must be shared with a wider network. A further study would look to follow patients newly diagnosed with coeliac disease from diagnosis and over a longer period of time. Additionally, we would also like to cognitively evaluate people who are diagnosed with coeliac disease having been referred first to a neurologist as opposed to a gastroenterologist. We deliberately excluded such patients from this study. It is possible that the scale of the problem is much bigger than what we have found.

There is a need to highlight the symptoms of coeliac disease beyond the gut to both aid early diagnosis and to encourage patients to maintain a strict gluten free diet for life. This is particularly important because neurological recovery may be limited if the diagnosis is made late or the diet is not followed adequately.

Project Title: The humanistic and economic burden of coeliac disease in the UK; a follow up study 

Dr Mara Violato is a senior researcher in health economics and research lecturer at the University of Oxford.

What were the main issues your research was seeking to address?

This project aimed to evaluate whether the time to medical diagnosis, from the appearance of the first symptoms associated with coeliac disease, has shortened over time.It also planned to assess how coeliac disease affects people’s quality of life, before and after diagnosis, and how this varies over time, by geographic area of the UK, and by socioeconomic group.The results would then be compared with a similar survey carried out in 2006. The project also aimed to quantify the costs of coeliac disease to patients and the NHS and the impact that has on patients’ families.

How successful was the project in achieving this?

Very successful, as we managed to conduct a large survey to collect important evidence based information for the aims of the project.

What are the key things that were learnt as a result of this project?

• Despite recent improvements in methods to detect coeliac disease, it still takes on average 13 years, from onset of symptoms, to achieve a diagnosis.
• The average score for quality of life was reported lower before diagnosis and improved by about 30% after diagnosis, to a level very similar to the quality of life reported by the general population of England.
• Regions where the average quality of life before diagnosis was lower than the UK average, were Northern Ireland, Scotland, the North East of England, the West Midlands, and the London area.
• The highest quality of life improvement between pre- and post diagnosis, was registered in the London area.
• The lower the family income, the lower the health score reported by the participants. Differences in health status by income were even more noticeable in the group of participants who relied on gluten free food on prescription and had their prescriptions restricted.
• When asked how restrictions on prescriptions of gluten free food affected the affordability of an adequate gluten free diet, 21% of respondents admitted they could not always afford to purchase the same amount or variety of gluten free food that they were used to having on prescription, and another 21% were only just managing.
• After diagnosis, people with coeliac disease experienced a number of out-of-pocket expenses related to the management of their health condition. These included costs of private medical consultations, over-the-counter medications, gluten free products, nutritional supplements, and books, DVDs or videos on symptoms management.
• Coeliac disease and its management was reported to have a negative impact on the people (family and friends) close to the person with the condition. They felt limited in a number of daily situations (eg restaurants, holidays and family events), and 61% of them reported to be moderately or extremely worried about the person’s health and wellbeing following her/his diagnosis.

How will this project benefit patients?

This research provides up to date evidence to support raising the awareness of the emotional and economic burden that patients and the NHS have to bear and the impacts of all this on patients’ families. The evidence will also be of use to researchers evaluating the cost effectiveness of possible future prevention, treatment or cure.

How has the funding from Coeliac UK made a difference?

We are extremely grateful to Coeliac UK for funding this study and for practical support in conducting the survey, without this support the survey would not have happened.

Project Title: Catering research – providing information for caterers to produce safe gluten free meals. Developing a gluten free risk assessment ‘toolkit’ for the catering sector 

We know that eating out is a top priority for people with coeliac disease. We know that if you could, you would eat out more and that you are willing to travel some distance to be sure to find a gluten free meal. When the law on gluten free was published in 2009, caterers had three years to comply with the law. We wanted to be able to advise caterers on how to cater for people on a gluten free diet and to provide tools to help them cater for you. We commissioned two projects in 2010 and 2012 to provide us with information to inform the catering sector.

We commissioned a research project to investigate the levels of gluten found in meals served for people with coeliac disease. The project also looked at the controls that were in place, the processes used to produce gluten free meals and information on the training provided. The project involved a variety of catering establishments including a school, hospital, workplace canteen, independent restaurants and large restaurant chains.

The results from this project were very encouraging, with 95% of samples testing as gluten free in line with the law. This project enabled us to produce our online training module, face to face training course, flipbook and poster.

Project Title: Evaluation of risks and necessary controls for gluten free production in a commercial kitchen environment that simultaneously uses wheat flour 

This project was designed to establish more precise recommendations on the conditions necessary to provide gluten free food whilst gluten containing flour was in use within the same commercial kitchen.

This work developed an understanding of the impact of the method of cooking, segregation, spatial arrangement within the kitchen and will be used to make specific recommendations for caterers preparing gluten free meals in kitchens where gluten containing flour is also handled.

Associated publications:

Miller K, Mc Gough N, Urwin H. 2016 Catering Gluten-Free When Simultaneously Using Wheat Flour. Journal of Food Protection, Vol. 79, No. 2, 2016, Pages 282–287

Project Title: The genetic basis of coeliac disease 

Knowing the genetic basis for coeliac disease is really important. It means we could potentially find new treatments for the condition and find out what the triggers for coeliac disease are. And if we know why people with the genes get coeliac disease, maybe one day we can stop it altogether.

That’s why we funded this research project with Professor David van Heel, a Professor of Genetics at The London School of Medicine and Dentistry, and consultant gastroenterologist at Barts Health NHS trust. David’s research interests include autoimmune diseases and the immunological consequences of disease predisposing genetic variants on human biology. Here we find out more about his research and what was achieved.

What was the main issue your research was seeking to address?

We know from studies in families and in twins that coeliac disease has a strong genetic tendency, with close family members having a 10% chance of developing the disease themselves. We also know nearly all people with coeliac disease have HLA-DQ2/DQ8 type, but this type is also found in about third of healthy individuals. The HLA-DQ2/DQ8 type is therefore necessary but not sufficient to develop the disease. However, the reason for this is not fully understood.

What were you hoping to find out through this research? How successful were you?

We were hoping to reveal inherited factors which might explain why some people develop coeliac disease. We performed a study testing over 300,000 genetic variants in 778 individuals with coeliac disease and 1,422 without, which in total provided over 600 million measurements. We compared the frequency of each variant in people with and without coeliac disease.

What are the key things that were learnt as a result of this project?

A small number of the 300,000 genetic variants are found to occur more commonly in coeliac disease, enabling us to find some of the genes that appear to be important. Our first finding was the interleukin-2 and interleukin-21 genes, these are important in determining how strong an immune response is made. We have found a further seven gene regions that might predispose to coeliac disease and we have now studied about 7,000 samples from the UK and Europe.

How will this project benefit patients?

Having identified such gene regions that might predispose coeliac disease, we can study exactly how these gene variants cause coeliac disease. Understanding the ways in which genetic variants alter the immune system is important for finding new treatments.