Jason Tye-DIn-Projects

Jason Tye-DIn-Projects


We are seeking volunteers for several studies in coeliac disease and gluten sensitivity. We would love to hear from you!
If you wish to see if you are eligible to participate, visit our clinical studies page
Super Content: 
Clinician and patient in a consulting room

Our researchers are leading clinical studies into coeliac disease. Our studies involve volunteers with coeliac disease and gluten sensitivity, as well as healthy volunteers.

Find out how you can participate.

Dr Jason Tye-Din and Dr Melinda Hardy holding oats in lab

We have discovered how oats incite a harmful immune response in 8 per cent of people with coeliac disease

How does gluten make people with coeliac disease and gluten sensitivity sick?

Our studies in adults and children with coeliac disease have provided detailed knowledge of the key parts of gluten harmful to people with coeliac disease. However, how gluten triggers adverse symptoms such as vomiting, pain or diarrhoea in people with coeliac disease is poorly understood. Understanding this process will help in the development of better treatments to treat or prevent gluten-induced symptoms and also define better ways to measure symptoms, which can be helpful in clinical studies of new treatments.

This study is examining immune responses in the blood and small intestine after people with coeliac disease, gluten sensitivity and healthy volunteers consume a small amount of gluten. Testing will involve a detailed study of the immune cells and the proteins produced by this reaction and which genes are turned on. The results will provide important insight into how symptoms occur to gluten and potentially define targets suitable for treatment to better manage symptoms and biomarkers that are linked to symptoms.

Establishing the safety of oats in coeliac disease

The safety of oats for people with coeliac disease is controversial. Australia and New Zealand exclude oats from the gluten-free diet due to safety concerns, but many other countries do not. Oat is a nutritious grain that is high in fibre and has a range of health benefits, but it is important to determine if they can be safely consumed by people with coeliac disease.

We have shown that a proportion of people with coeliac disease have T cells that are triggered by oats or purified oats protein (avenin) to promote an inflammatory response, potentially putting them at risk of harm. This study aims to definitively determine if oats are safe to consume in coeliac disease, if safety can be determined by an immune blood test or food test, and whether a specific type or dose of oats is necessary for safe consumption.

This study involves the consumption of contamination-free oats or oat protein, immune blood tests and for some, gastroscopy and biopsy of the small bowel.

Why does the gluten-free diet fail?


The gluten-free diet is the main treatment for coeliac disease, yet many patients continue to have intestinal damage or experience symptoms despite following the diet for many years strictly. Ongoing intestinal damage is concerning as it is associated with a higher rate of complications such as osteoporosis, refractory coeliac disease and cancers such as lymphoma.

This project is investigating the reasons why the gluten-free diet fails in some patients despite their best attempts to exclude gluten. While it is assumed that low amounts of inadvertent gluten exposure is responsible for dietary failure, the actual causes for this have not been systematically addressed. This ongoing study is exploring the role of gluten contamination in commercial gluten-free foods and gluten-free products sold in food outlets, examining food handling, labelling and testing practices in industry, and looking at patient factors that contribute to knowledge and compliance to the diet.

The findings will inform targeted strategies to improve gluten-free diet outcomes for people with coeliac disease. 

What is the role of the microbiome in coeliac disease?

Specific susceptibility genes, such as HLA-DQ2 and/or HLA-DQ8, are critical for the development of coeliac disease. However, environmental factors are also important, and they may act as ‘triggers’ of disease. How they might do this is a very important yet unanswered question.

Emerging evidence suggests an important role for the eco-system of microbial organisms in the gastrointestinal tract, termed the ‘microbiome’, in coeliac disease development.  For example, studies undertaken with collaborators Professor Elena Verdu (McMaster University, Canada) and Professor Jamie Rossjohn (Monash University) have implicated Pseudomonas bacteria in coeliac disease development via a number of different mechanisms. This raises the possibility that specific alterations in the microbiome may have an important effect on gluten immunity and could affect the risk for coeliac disease development in genetically susceptible people.

Assessing spleen function and infection risk

The spleen plays a crucial role in antibody generation and defense from infections.

In people with coeliac disease, spleen function can be impaired (‘hyposplenism’), but the size of this issue is unclear and there is no Australian information. Hyposplenism is associated with higher rates of infections, including serious ones such as pneumococcal pneumonia.

This study is assessing spleen function in people with newly diagnosed and treated coeliac disease to determine how hyposplenism affects immune function and the risk of infections. The study will also examine the adequacy of vaccination responses and how to best prevent serious infections.

Assessing non-invasive tools that measure accidental gluten intake


Establishing how well a person is following a gluten-free diet is difficult. Current tools rely on assessing a person’s dietary patterns or using antibody tests or intestinal biopsy, but these only indirectly reflect gluten exposure and they are not very helpful at determining if gluten is still being consumed.

This study is assessing a new technology designed to measure gluten (specifically, fragments of gluten called peptides) in a person’s stool (faeces) or urine. This gluten immunogenic peptide (GIP) assay is highly sensitive for detecting tiny amounts of gluten ingested by a person. They offer the potential to help doctors determine when a person with coeliac disease who is following a gluten-free diet is actually consuming gluten.

Our studies have shown that the GIP test can detect extremely small amounts of gluten present in stool samples and that symptoms and coeliac serology are very poor predictors of gluten intake compared to this sensitive stool test. Many people with treated coeliac disease and normal coeliac serology had evidence of gluten in the stool, indicating unintended gluten exposure. We are now examining why so many people with treated coeliac disease have inadvertent gluten exposure and understand the significance of low level detection.

New treatments for coeliac disease

Current treatment of coeliac disease necessitates a lifelong gluten-free diet. This diet needs to be strict to exclude gluten from causing damage in the body. Unfortunately, many people with coeliac disease do their very best to follow a strict gluten-free diet but continue to experience persistent damage to their small intestine or persistent symptoms. Effective treatments that make the current gluten-free diet more effective, or replace it altogether, are needed. If tolerance to gluten can be restored, it may be possible for people with coeliac disease to safely resume a normal gluten-containing diet.

Our team are currently testing a range of new treatments for coeliac disease. These include approaches that aim to reduce gluten in the body or its ability to reach the immune system and approaches that target the immune system and aim to reduce the abnormal response to gluten.

For most of our studies, participants do not need to consume any experimental medications. Rather, we often use a gluten challenge to help us assess new therapies.

Read more about gluten challenge here to learn how it can help us test new treatments and understand more about coeliac disease.

A simple blood test to diagnose coeliac disease that avoids the need for gastroscopy and gluten challenge

Early diagnosis of coeliac disease is important because it expedites treatment with a gluten-free diet and the journey to recovery and improved health. The current diagnosis of coeliac disease depends on antibody testing (coeliac serology) and a gastroscopy to sample the small intestine. Both of these tests are only accurate if gluten is being consumed. Unfortunately, many people in the community who may have coeliac disease have started a gluten-free diet, rendering current tests unhelpful for diagnosis. A prolonged gluten challenge is necessary but is often tolerated poorly.

We are developing a blood-based diagnostic test for coeliac disease based on the measurement of a chemical (interleukin-2) that is produced in significant amounts in the blood of people with coeliac disease after exposure to gluten but not those without coeliac disease. Interleukin-2 is also detectable in a test tube when the blood from someone with coeliac disease is mixed with gluten if we employ an ultra-sensitive cytokine detection machine (Figure 1).  Our goal is to develop a blood test to diagnose coeliac disease without the need for a person to deliberately consume gluten or have to undergo an invasive gastroscopy.

Diagram of Interleukin-2 diagnostic test
Figure 1. Interleukin-2 diagnostic test
Gluten triggers release of a chemical called interleukin-2 in the blood of people with coeliac disease but not those without. This new diagnostic approach may avoid the need for a gastroscopy or people having to consume gluten to make testing accurate.


Non-responsive and refractory coeliac disease

A small proportion of people with coeliac disease (1-2%), usually those older than 50, can develop a serious complication called refractory coeliac disease. Patients with this complication experience prominent symptoms such as diarrhoea and weight loss, and have significant small intestinal inflammation, despite following a strict gluten-free diet for over a year. Refractory coeliac disease is concerning because it is associated with an increased risk of certain cancers, called lymphomas. Unfortunately, treatment options are limited.

Our goal is to develop better approaches to treat and diagnose this complication. We have several studies examining why refractory coeliac disease occurs and a study evaluating the efficacy of current treatment approaches.

Other studies underway

We have a range of other studies underway. For more information email coeliac@wehi.edu.au (preferred) or call +61 3 9345 2300 and leave a message.

  • Understanding and measuring brain fog in coeliac disease
  • Using genomic risk scores to understand the likelihood of coeliac disease developing
  • We are involved in the ENDIA study to examine genetic and environmental factors involved in the development of type 1 diabetes and coeliac disease

Clinical trials

There are a range of exciting clinical trials commencing in 2022 that will be testing new therapies in coeliac disease. These will be conducted across the Royal Melbourne Hospital and WEHI and more details will be posted soon.