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

Objective: The primary aim of the research initiative was to clarify the relationship between gut microbiota and metabolomic profiles in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN). To aim for discovery for new biomarkers and clarify their roles in the underlying mechanisms linked to disease development and advancement.Methods: Fecal samples from 15 healthy controls (HC) and 36 SLE patients (18 with LN and 18 without LN) were subjected to 16S rRNA gene sequencing and untargeted metabolomics. Comprehensive analyses of the diversity metrics, differential microbial taxa, and metabolite profiles were conducted. Microbial diversity was explored using Principal Coordinate Analysis (PCoA) and Non-metric Multidimensional Scaling (NMDS), while the key taxa and metabolites were identified through Linear Discriminant Analysis Effect Size (LEfSe) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). KEGG pathway and ROC curve analyses were used to evaluate the clinical relevance of the identified metabolites.Results: Beta diversity analysis exhibited profound statistical variations in microbial composition between the SLE (with and without LN) and HC groups, despite similar alpha diversity. The prevalence of Firmicutes was higher in SLE, whereas that of Proteobacteria increased with disease progression to LN. Metabolomic analysis identified 177, 159, and 94 differential metabolites in the HC vs. LN, HC vs. SLE, and SLE vs. LN comparisons, respectively. Key findings include elevated levels of mead acid and reduced palmitoylcarnitine levels in patients with LN. Significant alterations were observed in metabolic pathways, such as taurine and hypotaurine metabolism and primary bile acid biosynthesis. Glycocholic acid (AUC = 0.951) and glycochenodeoxycholic acid (AUC = 0.827) demonstrated a high diagnostic potential for distinguishing between SLE and LN.Conclusion: This study reveals significant variations in gut microbiota and metabolites associated with SLE