A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls

Abstract

BackgroundFibromyalgia syndrome (FMS) is a chronic pain syndrome. A plausible pathogenesis of the disease is uncertain and the pursuit of measurable biomarkers for objective identification of affected individuals is a continuing endeavour in FMS research. Our objective was to perform an explorative metabolomics study (1) to elucidate the global urinary metabolite profile of patients suffering from FMS, and (2) to explore the potential of this metabolite information to augment existing medical practice in diagnosing the disease.MethodsWe selected patients with a medical history of persistent FMS (n = 18), who described their recent state of the disease through the Fibromyalgia Impact Questionnaire (FIQR) and an in-house clinical questionnaire (IHCQ). Three control groups were used: first-generation family members of the patients (n = 11), age-related individuals without any indications of FMS or related conditions (n = 10), and healthy young (18–22 years) individuals (n = 20). All subjects were female and the biofluid under investigation was urine. Correlation analysis of the FIQR showed the FMS patients represented a well-defined disease group for this metabolomics study. Spectral analyses of urine were conducted using a 500 MHz 1H nuclear magnetic resonance (NMR) spectrometer; data processing and analyses were performed using Matlab, R, SPSS and SAS software.Results and discussionUnsupervised and supervised multivariate analyses distinguished all three control groups and the FMS patients, and significant increases in metabolites related to the gut microbiome (hippuric, succinic and lactic acids) were observed. We have developed an algorithm for the diagnosis of FMS consisting of three metabolites — succinic acid, taurine and creatine — that have a good level of diagnostic accuracy (Receiver Operating Characteristic (ROC) analysis — area under the curve 90%) and on the pain and fatigue symptoms for the selected FMS patient group.ConclusionOur data and comparative analyses indicated an altered metabolic profile of patients with FMS, analytically detectable within their urine. Validation studies may substantiate urinary metabolites to supplement information from medical assessment, tender-point measurements and FIQR questionnaires for an improved objective diagnosis of FMS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-017-0863-9) contains supplementary material, which is available to authorized users.

Metabolic fingerprinting for diagnosis of fibromyalgia and other rheumatologic disorders

“…According to the investigators, lysophosphocholine dominated the metabolite profile, suggesting that there may be additional potential biomarkers for FM diagnosis (17). Recently, Malatji et al (18) used NMR metabolomics to identify a diagnostic biomarker profile for FM from urine, identifying metabolites associated with indicators of pain and fatigue symptoms (succinic acid, taurine, and creatine) and perturbations in the gut microbiome (hippuric, 2-hydroxyisobutyric, and lactic acids).…”

Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review

“…1) shows the selection process and number of studies included and excluded at each step to arrive at the final eleven studies, conducted in 7 countries, included in this analysis. There was a high degree of heterogeneity across the studies, which were of variable quality ( (22)(23)(24)(25), and three reported other biomarkers (16,21,26). Four studies (16,(21)(22)(23) examined more than one type of biomarker and so are included in each of the appropriate sections below.…”

Metabolomic Differentials in Women With and Without Fibromyalgia

“…Similarly, we found elevated levels of taurine, a sulfur-containing amino acid whose pathway is understood to be associated with alterations in lipid metabolism in women. 29 Elevated levels of taurine have been previously reported in serum 30,31 and urine 32 in women diagnosed with FM. Similarly, elevated levels of methionine sulfoxide and anthranilate have been reported.…”