Exploratory Fecal Metabolomics of Rheumatoid Arthritis Reveals Candidate Biomarkers

ABSTRACT

Rheumatoid arthritis (RA) is a chronic autoimmune disease in 1% of the global population, yet 20%–30% of seronegative patients remain undiagnosed. This current study aims to explore the nature of fecal biomarkers and investigate gut–joint axis dysfunction using untargeted metabolomics analysis and multivariate analysis. We conducted a case‐control study, recruiting 16 treatment‐naïve patients with rheumatoid arthritis and 20 age‐matched healthy individuals (HI) from the Vietnamese population. Their fecal extracts were analyzed by high‐resolution mass spectrometry and chemometric processing, and metabolites were putatively annotated using different libraries. The Orthogonal Partial Least Squares Discriminant Analysis model demonstrated significant discrimination ( Q ² = 0.6 and R ² Y = 0.885) between two categories. Seven fecal putatively annotated biomarkers were proposed based on variable importance in projection (VIP) scores, receiver operating characteristic (ROC) curve analysis, and area under the curve (AUC) evaluation, which were significantly depleted in the patient group. Additionally, enrichment analysis and correlations between fecal metabolites and plasma biochemical parameters highlight the potential of these metabolites as candidate biomarkers, including O ‐phosphoethanolamine, stearic acid, 1‐monopalmitin, nicotinic acid, and diallyl trisulfide (DATS). Although this study still needs a longitudinal study with a greater population size to validate the candidate biomarkers, these findings have contributed to the exploration of fecal metabolomes in the discovery of rheumatoid arthritis.