Gut microbiome dysregulation is associated with segmental glomerulosclerosis in IgA nephropathy: insights from Oxford classification-based microbiome profiling

Background: IgA nephropathy (IgAN) is a common immune-complex-mediated glomerulonephritis with segmental glomerulosclerosis (S lesion, S1 in Oxford classification) being an independent predictor of poor renal prognosis, where 20%-40% of IgAN-S1 patients progress to end-stage renal disease, but its pathogenesis is unclear. Methods: This study enrolled 12 IgAN-S0 (without segmental sclerosis) and 19 IgAN-S1 (with segmental sclerosis) patients, performed 16S rRNA gene sequencing on fecal samples, and analyzed gut microbiota composition and functions. Results: S1 had enriched Firmicutes and Patescibacteria while S0 had more Proteobacteria, Campylobacterota, and Desulfobacterota; LEfSe analysis identified Subdoligranulum and unclassified_Erysipelotrichaceae_UCG-003 as S1-specific biomarkers and Phascolarctobacterium, Streptococcus_parasanguinis, and Proteobacteria as S0 biomarkers (P