Metabolomics approach by 1H NMR spectroscopy of serum reveals progression axes for asymptomatic hyperuricemia and gout

Background: Gout is a metabolic disease and is the most common form of inflammatory arthritis affecting men. However, the pathogenesis of gout is still uncertain, and novel biomarkers are needed for early prediction and diagnosis of gout The aim of this study was to develop a systemic metabolic profile of patients with asymptomatic hyperuricemia (HUA) and gout by using a metabolomics approach, and find potential pathophysiological mechanisms of and markers of predisposition to gout. Methods: Serum samples were collected from 149 subjects, including 50 patients with HUA, 49 patients with gout and 50 healthy controls. H-1 nuclear magnetic resonance (NMR) spectroscopy combined with principal components analysis and orthogonal partial least squares-discriminant analysis were used to distinguish between samples from patients and healthy controls. Clinical measurements and pathway analysis were also performed to contribute to understanding of the metabolic change. Results: By serum metabolic profiling, 21 metabolites including lipids and amino acids were significantly altered in patients with HUA or gout The levels of identified biomarkers together with clinical data showed apparent alteration trends in patients with HUA or gout compared to healthy individuals. According to pathway analysis, three and five metabolic pathways were remarkably perturbed in patients with HUA or gout, respectively. These enriched pathways involve in lipid metabolism, carbohydrate metabolism, amino acids metabolism and energy metabolism. Conclusions: Taken together, we identified the biomarker signature for HUA and gout, which provides biochemical insights into the metabolic alteration, and identified a continuous progressive axis of development from HUA to gout.