Caution in studying and interpreting the lupus metabolome

Several metabolomics studies have shed substantial light on the pathophysiological pathways underlying multiple diseases including systemic lupus erythematosus (SLE). This review takes stock of our current understanding of this field. We compare, collate, and investigate the metabolites in SLE patients and healthy volunteers, as gleaned from published metabolomics studies on SLE. In the surveyed primary reports, serum or plasma samples from SLE patients and healthy controls were assayed using mass spectrometry or nuclear magnetic resonance spectroscopy, and metabolites differentiating SLE from controls were identified. Collectively, the circulating metabolome in SLE is characterized by reduced energy substrates from glycolysis, Krebs cycle, fatty acid β oxidation, and glucogenic and ketogenic amino acid metabolism; enhanced activity of the urea cycle; decreased long-chain fatty acids; increased medium-chain and free fatty acids; and augmented peroxidation and inflammation. However, these findings should be interpreted with caution because several of the same metabolic pathways are also significantly influenced by the medications commonly used in SLE patients, common co-morbidities, and other factors including smoking and diet. In particular, whereas the metabolic alterations relating to inflammation, oxidative stress, lipid peroxidation, and glutathione generation do not appear to be steroid-dependent, the other metabolic changes may in part be influenced by steroids. To conclude, metabolomics studies of SLE and other rheumatic diseases ought to factor in the potential contributions of confounders such as medications, co-morbidities, smoking, and diet.