1H NMR metabolic signatures of early paediatric type I diabetes

BSc. Alexandra Mižová

Master's thesis

Abstract:

Abstract Background: T1D is an autoimmune disorder marked by the destruction of insulin-producing β-cells in the pancreas. Faecal metabolites, reflecting factors such as gut microbiota composition and dietary influences, may serve as indicative biomarkers for T1D status and susceptibility. Analysing faecal metabolomic profiles holds potential in diagnosing and identifying increased risk for paediatric T1D, aiming to enhance early detection and management of the disease. Aim/ Hypothesis: This case-control study hypothesises that children at genetic predisposition for developing T1D exhibit distinct faecal 1H NMR metabolic profiles compared to healthy children. We propose that these faecal metabolic differences, potentially influenced by variations in gut microbiota composition or dietary patterns, may precede the clinical onset of T1D. Understanding these variations could offer valuable insights for the clinical diagnosis and early detection of T1D. Methods: This study analysed 87 faecal samples from 24 children (aged 4.8 years ± 1.2 years), genetically predisposed to T1D and their matched controls. The faecal metabolic profiles were evaluated using 1H NMR spectral analysis. The 1H NMR data were processed using NMRProcFlow 1.4 and Chenomx 9.02 software and statistically evaluated using MetaboAnalyst 6.0 to identify potential metabolic differences that could signify increased risk of T1D. Results: The study identified a statistically significant difference (p < 0.05) in the levels of the metabolite 3-(3-hydroxyphenyl)propionic acid, which were higher in the T1D-predisposed group than in the control group. While the specific biochemical function of this metabolite is not yet understood, it is speculated that variations in gut microbiota composition or dietary patterns among the T1D-predisposed children may account for the observed differences in metabolite concentrations. Conclusion: Our study findings suggest that differences in faecal metabolic profiles could aid in the early detection of T1D in paediatric populations. The identification of specific metabolites through 1H NMR spectroscopy underscores its utility as a powerful tool for pinpointing biomarkers associated with T1D risk and progression.

Keywords

metabolomics, faecal metabolic profiling, 1H NMR, biomarkers, T1D

Language used: English

Date on which the thesis was submitted / produced: 21. 4. 2024

Thesis defence

• Date of defence: 23. 5. 2024
• Supervisor: doc. Ing. Jaroslav Havlík, Ph.D.
• Reader: Zuzana Hroncová, Ph.D.

Czech University of Life Sciences Prague

Faculty of Agrobiology, Food and Natural Resources

Master programme:
Food and Nutrition