Metabolomics in systemic lupus erythematosus: A systematic review and meta-analysis

Systemic lupus erythematosus (SLE) still lacks highly specific biomarkers; high-throughput metabolomics offers a route to elucidate disease-defining metabolic perturbations.

This systematic review aims to identify common metabolite changes related to SLE.

PubMed, Web of Science, Scopus, and the Cochrane Library were searched through November 2024 for human observational studies comparing the metabolomic profiles of adult SLE patients with those of healthy controls. Random-effects meta-analyses used the ratio of means (RoM); heterogeneity was assessed using the I² statistic.

Forty-six studies comprising 2,238 SLE patients and 1,761 healthy controls (total n = 3,999) were included. Ten metabolites, each reported in ≥2 of the five eligible studies, were quantitatively synthesized. Compared with controls, isoleucine (RoM = 0.73, 95 % CI = 0.72-0.74, I² = 0 %), leucine (RoM = 0.81, 95 % CI = 0.80-0.81, I² = 0 %), and tryptophan (RoM = 0.73, 95 % CI = 0.64-0.84, I² = 75 %) were significantly lower in SLE, whereas methionine was significantly higher (RoM = 1.54, 95 % CI = 1.26-1.88, I² = 88 %). Lipid remodeling included elevated oleic acid (RoM = 1.42, 95 % CI = 1.19-1.69, I² = 0 %) and reduced capric acid (RoM = 0.80, 95 % CI = 0.67-0.95, I² = 31 %). Qualitative synthesis revealed consistent reduction of tricarboxylic acid intermediates, accumulation of acylcarnitines, and an oxidized-lipid signature (e.g., 9-hydroxyoctadecadienoic acid, leukotriene B4), implying mitochondrial stress and redox imbalance.

Metabolomic profiling identifies a reproducible SLE signature: relative to controls, branched-chain (isoleucine, leucine) and aromatic (tryptophan) amino acids are lower, methionine is higher, and lipid profiles show higher oleic and lower capric acids, patterns consistent with impaired mitochondrial energetics and altered one-carbon flux.