Uncovering Potential Biomarkers and Metabolic Pathways in Systemic Lupus Erythematosus and Lupus Nephritis through Integrated Microbiome and Metabolome Analysis

Objective This study aimed to elucidate the relationship between gut microbiota and metabolomic profiles in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) to identify potential biomarkers and elucidate their roles in disease progression. Methods Fecal samples from 15 healthy controls (HC) and 36 SLE patients (18 SLE-nonLN and 18 SLE-LN) were analyzed using 16S rRNA gene sequencing and untargeted metabolomics. Differential microbial taxa and metabolites were identified using Linear Discriminant Analysis Effect Size (LEfSe) analysis and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Receiver Operating Characteristic (ROC) curve analysis were employed to evaluate the clinical relevance of identified metabolites. Results Beta diversity analysis demonstrated significant clustering among groups ( p  < 0.05). SLE-LN exhibited increased Proteobacteria (28.02% vs. 12.93% in SLE-nonLN) and decreased Firmicutes (39.50% vs. 59.08%). Metabolomic profiling identified 94 differentially abundant metabolites in SLE-LN vs. SLE-nonLN, enriched in primary bile acid biosynthesis (e.g., Glycocholic acid, AUC = 0.951). SLE-nonLN displayed 159 differential metabolites compared to HC, including increased Glycoursodeoxycholic acid (AUC = 0.922) in taurine and hypotaurine metabolism. Microbial-metabolite correlation analysis highlighted Escherichia-Shigella as negatively associated with bile acids ( p  < 0.01). Conclusion This study reveals distinct gut microbiota and metabolomic signatures associated with SLE and LN. The identified microbial taxa and metabolites may serve as potential diagnostic biomarkers and therapeutic targets for disease management.