Metabolomics for monitoring of pathological mechanisms and response to therapeutic interventions

Gonzalez Marques Junior, Jair (2024): Metabolomics for monitoring of pathological mechanisms and response to therapeutic interventions. Dissertation, LMU München: Medizinische Fakultät

Abstract

This dissertation explores the application of mass spectrometry-based metabolomics to investigate pathological mechanisms and monitor therapeutic interventions. The research combines untargeted and targeted metabolomics approaches to analyze metabolic profiles associated with two major clinical conditions: Crohn’s disease in pediatric patients and sarcopenia in elderly patients. In the first two studies, untargeted metabolomics using high-resolution mass spectrometry was employed to examine the metabolic effects of nutritional therapies, specifically exclusive and partial enteral nutrition in children with Crohn’s disease. Significant alterations in the plasma metabolome were observed, including changes in inflammatory markers, xenobiotic metabolites, and bacterial byproducts. These findings highlight the potential of metabolomics for identifying metabolic signatures associated with disease state and treatment response, although causality remains to be established. The third study applied a targeted metabolomics platform to assess plasma levels of amino acids, bile acids, acylcarnitines, and fatty acids in patients with sarcopenia, a condition characterized by loss of muscle mass and function. The results identified metabolites such as citrulline and very long-chain fatty acids that are significantly associated with sarcopenia, suggesting a link to mitochondrial dysfunction. Overall, this work demonstrates that metabolomics is a powerful tool to gain insight into disease mechanisms and therapeutic efficacy, with potential applications in precision medicine and biomarker discovery.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Metabolomics, Crohn’s disease, Sarcopenia
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 10. Oktober 2024
• 1. Bericht­erstatter:in: Koletzko, Berthold