Metabolomics analysis of plasma identifies aberrant amino acids and lipids metabolism in the patients with acute anterior uveitis

Abstract

Background Acute anterior uveitis (AAU) is a severe ocular inflammatory disease and the metabolic characteristics are still unclear. To investigate the potential molecular biomarkers and to understand the metabolic response of AAU. Methods Untargeted plasma, which included 181 AAU patients and 99 non-uveitic controls, metabolomics analysis was conducted in this study based on ultra-performance liquid chromatography mass spectrometry (UPLC-MS). Results Eighteen and seven significant changed metabolites were found according to the variable importance in the projection value from orthogonal partial least-squares discriminant analysis (OPLS-DA), p value from univariate analysis and fold change for positive and negative mode, respectively. The AAU metabolomics signature indicated increased 10 amino acids (Glycyltyrosine, Pyroglutamic acid, L-Aspartyl-4-phosphate, Brassica oleracea Alkaloid, L-Glutamic acid, gamma-Glutamyl-S-methylcysteine sulfoxide, Tryptophyl-Glutamine, Diaminopimelic acid, 3-Aminoisobutanoic acid, Glycylproline), 7 lipids (3-Deoxyfructose, Maltitol, PC(20:2(11Z,14Z)/15:0), Cholesterol, PC(22:2(13Z,16Z)/16:1(9Z)), PC(16:1(9Z)/20:0), Cholesterol sulfate), one flavonoids (Quercetin) and two carbohydrates (Sorbitol, N-Acetylneuraminic acid), and decreased 5-Hydroxyindoleacetic acid, L-Histidine, Acetyl-N-formyl-5-methoxykynurenamine, Theophylline and 3-Hydroxybenzoic acid in AAU compare with the control group in both positive and negative modes. Pathway analysis indicated D-Glutamine and D-glutamate metabolism and Histidine metabolism were significantly altered in AAU. Several potential biomarkers for AAU diagnosis were selected by receiver operating characteristic curve (ROC) analysis. Conclusions Our study uncovers a significant difference of plasma metabolic profile for AAU disease. These changes of metabolites in plasma may improve our understanding of the pathophysiology of AAU disease. Further studies are still needed to validate our findings and investigate the function of altered metabolites.