Identification of urinary bacterial genes as biomarkers for non-invasive diagnosis of renal lupus

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BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that often affects the kidneys, causing lupus nephritis. Diagnosis of this affection currently relies on kidney biopsy, an invasive and complex procedure. This study explores the diagnostic value of biomarkers based in the urobiome - the microbial community of the urinary tract - in patients with renal SLE. METHODS: This study enrolled 585 female subjects including Healthy controls, non-renal and renal SLE patients. The taxonomic and functional differences of the urobiome in patients with SLE, as well as in the metabolites of interest, were identified by 16S rRNA profiling with PICRUSt functional inference and nuclear magnetic resonance (NMR). The accuracy of the identified biomarkers was tested by building random forest (RF) classification models. Furthermore, the results were validated in an independent cohort composed by 30 controls, 30 non-renal and 30 renal SLE patients. RESULTS: Bacterial gene-based biomarkers with an AUC value of 0.7 ± 0.07 and 0.67 ± 0.07 to distinguish renal from non-renal SLE cases were identified. These biomarkers were validated in a validation cohort using quantitative PCR (qPCR), demonstrating their robust diagnostic performance. Furthermore, our analysis uncovered significant urobiome dysbiosis and distinct bacterial functional profile in both groups of SLE patients, with notable differences in amino acid metabolism pathways, particularly those involving valine and leucine, which were assessed by NMR-based urinary metabolite quantification. CONCLUSIONS: Some bacterial genes have been identified in the urobiome of SLE patients that allow differentiation between those with renal and non-renal lupus. These findings offer valuable insight into the association between the urobiome and SLE presentation, and lay the foundation for developing novel diagnostic tools that overcome the limitations of current methods, thereby improving patient care.

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