Application of metabolomics in the classification of traditional Chinese medicine syndromes in rheumatoid arthritis.

Objective: Rheumatoid arthritis (RA) is frequently treated with traditional Chinese medicine (TCM), where patients are classified into distinct syndromes, such as heat-dampness syndrome (HD) and kidney-liver deficiency syndrome (KLD). However, an objective and systematic approach to differentiate these TCM syndromes remains lacking. This study is aimed at analyzing serum metabolomics to identify differential metabolites and pathways associated with HD and GS syndromes in RA patients and at evaluating their potential as diagnostic biomarkers.

Methods: Serum samples from RA patients classified into HD and KLD groups were analyzed using metabolomics. Partial least squares discriminant analysis was employed to identify significant metabolites, while pathway analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes database. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic potential of key metabolites.

Results: Fifteen differential metabolites and two perturbed pathways-sphingolipid and D-amino acid metabolism-were identified between the KLD and HD groups. Notably, several metabolites, including C17-sphinganine and leucyl-alanine, demonstrated high diagnostic efficacy, with area under the curve (AUC) values exceeding 0.90. Correlation analysis revealed significant associations between certain metabolites and clinical indices, further substantiating their role in syndrome differentiation.

Conclusions: This study presents a comprehensive analysis of serum metabolites in RA patients under different TCM syndromes. The identified metabolites hold potential as biomarkers for distinguishing HD and KLD groups, paving the way for more objective and evidence-based diagnostic approaches in TCM. Key Points • Differential metabolites were identified in the serum of RA patients with heat-dampness syndrome and kidney-liver deficiency syndrome, with their metabolic pathways primarily involving sphingolipid metabolism and D-amino acid metabolism. • Serum metabolites demonstrate high efficacy in distinguishing RA patients with different TCM syndromes. • Significant correlations were observed between serum differential metabolites and clinical indicators in RA patients with varying TCM syndromes.