Chief Investigator: Dr Roger Yazbek

Funding Amount: $74,406

Recipient: Flinders University

Overview:

Almost 1% of Australian children suffer with coeliac disease, with a large number still going undiagnosed. Current methods for the detection of coeliac disease are costly and invasive, leading to delays in diagnosis. New tests are needed that are non-invasive, rapid, and more suitable for a paediatric setting. We have developed a new, stable-isotope breath test that may detect the intestines ability to break down gluten. We will conduct a pilot study of this breath test in children with and without coeliac disease to provide proof-of-concept data for future, large scale clinical studies.

Research Outcomes:

Researchers: Dr Roger Yazbek, Dr David Moore, Professor Ross Butler, Associate Professor Cathy Abbott

Research Completed: 2022

Research Findings: Our research team has pioneered a new breath test technique to measure intestinal damage and function. Our data suggests that this breath test can detect small intestinal damage in children with coeliac disease and may reduce the need for future invasive hospital procedures, such as endoscopy, in children.

Key Outcomes:

Summary of Key Outcomes:

1.     Small intestinal DPP4 enzyme activity was reduced in children with active Coeliac disease

2.     Small intestinal DPP4 enzyme activity appeared to be higher in children with Coeliac disease in

        remission

3.     DPP4 breath test could potentially be used to detect and monitor intestinal damage in children with positive blood tests for Coeliac disease, minimising the need for endoscopy.

Summary:

Dr Yazbek has pioneered the development of the ¹³C-DPP4 breath test and spearheaded its application for small intestinal damage and dysfunction. The main aim of this project was to determine whether the ability to break down gluten related peptides by the small intestinal enzyme, DPP4, is impaired in children with celiac disease. Specifically, we aimed to quantify intestinal DPP4 activity in children with Coeliac disease, other intestinal mal-absorptive disorders and healthy controls using a ¹³C-DPP4 breath test.

Unfortunately, the COVID-19 pandemic had a significant impact on our study, resulting in a suspension of all clinical trial activity at the Women’s and Children’s Hospital during multiple South Australian lockdowns. This caused additional delays with endoscopic procedures either delayed or cancelled, impacting recruitment targets.

Despite these barriers, we recruited a total of n=23 study participants. Breath samples were collected from children presenting to the Women’s and Children’s Hospital. We recruited n=7 patients who were positive for active coeliac disease, n=5 Coeliac patients in remission and n=6 non-coeliac patients. Breath samples were analysed at Flinders University in Dr Yazbek’s laboratory.

DPP4 enzyme activity was detected by DPP4 breath test in all study participants, as indicated by an

increasing breath ¹³CO₂ over the 2-hour collection period.

The breath ¹³CO₂ was lower in patients with active disease compared to non-coeliac patients and those in remission. The lower signal corresponded with the small intestinal damage reported in these children.

Interestingly, there was a higher breath ¹³CO₂ signal detected in coeliac patients in remission compared to those with active disease and non-coeliac patients.

These novel findings suggest a possible adaptive response in the small intestine of children recovering from previous intestinal damage associated with coeliac disease (Figure 1).

Our preliminary findings suggest that the DPP4 breath test could be used to detect and monitor small intestinal damage and repair in children with Coeliac disease. Additional studies are ongoing to expand the study cohort and validate our findings.

We would like to acknowledge and thank the Channel 7 CRF for funding our project.

Childhood illnesses to benefit from new CRF funded research

Research Papers: The preliminary findings from this research were presented as a keynote presentation to the Coordinated Research Project study group of the International Atomic Energy Agency in October 2021. This group is investigating the “Application of Stable Isotope Techniques in Environmental Enteric Dysfunction Assessment and Understanding its Impact on Child Growth”.

Related Publications: The preliminary findings are also currently being prepared for publication, and the CRF will be duly acknowledged

Future Outcomes: