Investigation of metabolic biomarkers: A metabolomics approach

Publisher:
Elsevier
Publication Type:
Journal Article
Citation:
Toxicologie Analytique et Clinique, 2022, 34, (3), pp. s57
Issue Date:
2022-09
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Aim Metabolomics is a powerful emerging approach increasingly used as a characteristic fingerprint in clinical sciences. Metabolites are crucial for cellular functions whereby biological disturbances can cause a series of metabolic changes in the body. Metabolomics entered the toxicology field over a decade ago, showing rapid growth in the comprehensive analysis of plasma, urine and tissue extracts. This study aims to investigate human metabolic signature(s) through an untargeted metabolomics cerebrospinal fluid (CSF) study and a targeted metabolomics urinary pilot study. Method An untargeted CSF metabolomics study investigated a cohort of fourteen patients with acute encephalitis and age-matched non-inflammatory neurological disease controls (n =14). Cerebrospinal fluid metabolites were analysed using liquid chromatography coupled to high resolution mass spectrometry followed by subsequent multivariate and univariate statistical methods. The targeted metabolomics study explored the urinary neurotransmitter levels using a fully validated “dilute-and-shoot” LC-MS/MS method. For this study twenty regular cannabis users were assigned to consume 200mg of medical graded cannabidiol capsules per day (Biosynthesis Pharma Group UK) for a period of ten weeks. Results The untargeted CSF profiling showed metabolic differences between the patient and control groups using supervised orthogonal partial least squares discriminant analysis and further analysis of variance and Fisher's least significant different post hoc analysis presented thirty-five metabolites were significantly involved. The tryptophan-kynurenine, nitric oxide and GABA-glutamate metabolism and neopterin were key pathways contributing to the statistical discrimination. The targeted cannabidiol pilot study showed significant change from baseline to post-treatment: increases were observed for glutamate (P .0001) whilst gamma amino butyric acid (GABA) decreased (P .001). Conclusion The clinical study demonstrated
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