Investigating the potential of a metabolomic biomarker for pancreatic exocrine insufficiency

Powell-Brett, Sarah (2024). Investigating the potential of a metabolomic biomarker for pancreatic exocrine insufficiency. University of Birmingham. Ph.D.

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Abstract

Pancreatic exocrine insufficiency (PEI) is a reduction in pancreatic enzymes to a level below that required to maintain normal digestion. It is a consequence of many diseases, leading to malnutrition, impaired of quality of life and poor clinical outcomes. Diagnosis of PEI is challenging. This thesis investigates the potential for a novel diagnostic measure of PEI using metabolomics as a discovery tool.

The use of metabolomics, the study of the small products of metabolism, in developing novel biomarkers is a rapidly expanding field. This body of work is based on the hypothesis that: A fatty test meal will create a dynamic, measurable response in the food metabolome and that response will be different in those with PEI compared to healthy controls. To test this hypothesis, a trial called DETECTION was designed to obtain fed and fasted plasma samples from patients with PEI alongside healthy controls and use untargeted metabolomics to explore differences in their metabolomic response to a test meal. To accurately determine PEI status, the \(^{13}\)Carbon mixed triglyceride breath test (\(^{13}\)C MTGT) has been used alongside other markers of PEI. Much of this work has been directed towards developing and refining the \(^{13}\)C MTGT for use alongside blood metabolite analysis.

In summary, I have created an evidence-based protocol and novel test meal for the \(^{13}\)C MTGT that is compatible with post-prandial metabolite analysis. With the results of the DETECTION trial PEI screen, I have evaluated the prevalence of PEI in various patient groups and explored concordance between existing diagnostic tests for PEI. Finally, I have compared the postprandial metabolome of those with and without PEI and found significant differences that have the potential to be used as a biomarker for PEI, this is novel, ground-breaking and has the potential to greatly improve diagnosis and treatment of PEI.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):