A metabolomics investigation of Fibromyalgia Syndrome
This thesis, entitled: "A metabolomics investigation of Fibromyalgia Syndrome", deals with Fibromyalgia Syndrome (FMS), a chronic widespread pain disorder with an estimated prevalence of 3.2% in the South African general population. Currently, the pathophysiology of FMS is uncertain, and is difficult to diagnose because diagnosis is based, almost completely, on patient feedback. No putative biomarkers have been described for this disorder, as of yet. The quest to identify reliable biomarkers for definitive diagnosis and monitoring of disease progression forms an important aspect of FMS research. I present here an extensive metabolomics investigation using a clinically, well described FMS group in a thesis structured into three sections. Section one contains three chapters that primarily cover my study and the literature. Chapter 1 gives an overview of the thesis and describes the content of each chapter. Chapter 2 is the review on FMS from a clinical aspect. Here I define pain, from a biochemical view, and discuss the different kinds of pain associated with FMS. Chapter 2 also includes the detailed information on the clinical profile of the FMS patients, as well as information on the controls. Against this background I formulated my biological question: "Is there a metabolic perturbation in FMS that may subsequently be used to establish a pain profile for the disorder and to identify a biomarker or biosignature for FMS?". Chapter 3 is a review of the genetic component of FMS and I also introduce the investigative method employed in this study. Chapter 3 also reviews the three, key publications of the only other investigations that, likewise, studied FMS from a metabolomics aspect, during the course of my study. Section two (Chapter 4) I present an untargeted proton magnetic resonance (1H NMR) spectroscopy study on the urine of FMS patients and controls. This holistic 1H-NMR metabolomics approach proved to be useful in that the findings revealed that my FMS cohort was metabolically distinguishable from my controls on the basis of their urinary metabolic profiles. Section three (Chapter 5) focuses on a semi-targeted gas chromatography-mass spectrometry (GC-MS) study of the same FMS patients and control cohort as that in Chapter 4, with urine once more being used as the sample material. This was a follow-up study that was conducted on the basis of the findings from the 1H-NMR study in Chapter 4. Outcomes of this GC-MS study revealed further insights on the disorder, FMS, and we speculated a further mechanism that may underlie the pathophysiology of FMS. In the last section (Chapter 6), I discuss the achievements of this thesis. Here, I address the aims and objectives of this thesis and discuss the new mechanism we hypothesize to play a role in FMS pathophysiology, that may give rise to the phenotype observed in FMS. I conclude this study by speculating that 2-hydroxyisobutyric acid may be a potential putative biomarker for the metabolic perturbation occurring in FMS, as well as other diseases, as discussed in a brief overview.