Metabolomic Differentials in Women With and Without Fibromyalgia

Abstract

A nontargeted plasma metabolomic analysis was conducted to compare differentially expressed metabolites in women with and without fibromyalgia (FM) using data and samples collected from two parent studies in women with FM (n = 20) and comparative data collected from newly recruited age‐matched women (n = 20). Blood plasma samples were analyzed for metabolite content using liquid chromatography mass spectrometry. Consolidation of positive and negative ion mode metabolomics data with fold change (>2 or <0.5) and variable importance of projection scores ≥1 revealed statistically significant metabolites comparing samples from women with and without FM. Metabolite profiles in patients with FM differed from the comparison group in energy, lipid and amino acid metabolites reflecting heightened oxidative stress, inflammation, and tryptophan degradation in patients with FM. Study results may contribute to further identification of unique metabolomic profiles enhancing understanding of the pathophysiology of FM and for the development of effective therapeutic options.

Exploring Associations Between Metabolites and Symptoms of Fatigue, Depression and Pain in Women With Fibromyalgia

“…Recently, both carnitine and butyrobetaine have been linked to accelerated atherosclerosis due to their metabolic conversion by gut bacteria into trimethylamine-N-oxide (Minkler et al, 2015). In the original report of our study findings (Menzies et al, 2020), 5% of the study sample reported comorbid heart disease and 40% reported high blood pressure. It may be that l-carnitine and butyrobetaine play contributing roles in this regard as the positive relationship between these two metabolites and pain severity suggest the possibility of lipid oxidation.…”

“…The parent study participant inclusion criteria were >18 years; female with a current diagnosis of FM based on the 1990 American College of Rheumatology criteria (Wolfe et al, 1990) as confirmed by a letter from the participants’ primary care provider or rheumatologist; able to speak and read standard English; a minimum of a 6th grade education level; and, ability to understand and sign the consent form and complete study instruments. Exclusion criteria were other systemic rheumatologic conditions or immune disorders such as systemic lupus erythematosus, rheumatoid arthritis, HIV/AIDS; systemic use of corticosteroids; history of epilepsy; currently pregnant; or presence of a psychiatric disorder, such as a history of psychosis, schizophrenia, or bipolar disorder (Menzies et al, 2020). Consented and enrolled participants provided baseline information on symptoms of fatigue, depression, and pain, and provided 3 cc of blood for study-related biomarker identification.…”

“…Consented and enrolled participants provided baseline information on symptoms of fatigue, depression, and pain, and provided 3 cc of blood for study-related biomarker identification. Our sample and data quality control protocols have been previously described in detail (Menzies et al, 2020). In brief, blood samples were collected from participants, plasma was isolated via centrifugation, and multiple aliquots frozen at −80 °C in order to avoid multiple freeze thaw cycles prior to metabolomics analysis.…”

“…Banked plasma was selected based on availability of sufficient samples and matched with de-identified baseline symptom data (fatigue, depression, pain). Inclusion and exclusion criteria and protocol methodology, including the procedure for conducting global metabolomic profiling were reported in a previous publication (Menzies et al, 2020). Demographic and symptom data have been previously described in detail and are also summarized in Tables 1 and 2, respectively.…”

“…At present, much of the driving force in the precision health movement has been due to innovations in “omics” research. Among them is metabolomics, a promising approach that has become an important phenotyping technique with the potential to identify upstream biological events and epigenetic changes, to explain pathophysiological mechanisms underlying a disease or syndrome, as well as to propose new therapeutic targets for alternative treatments (Mastrangelo & Barbas, 2017; Menzies et al, 2020) The value of examining metabolic markers in body fluids is that disease-specific molecules that are leaked or secreted into body fluids can be quantified (Nordström & Lewensohn, 2010). Discriminating metabolites can then be identified and relationships between metabolomic profiles and clinical variables such as fatigue, depression, or pain can be examined (Young et al, 2013).…”