Gut microbiome dysregulation is associated with segmental glomerulosclerosis in IgA nephropathy: insights from Oxford classification-based microbiome profiling
Abstract
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<0.05). Functional prediction showed S1 was enriched in pro-inflammatory pathways like endoplasmic reticulum stress and secondary bile acid biosynthesis, while S0 had activated protective pathways such as cytochrome P450 drug metabolism and ubiquitin system. Conclusions This study reveals gut microbiota dysregulation is closely associated with IgAN segmental sclerosis, with S1 showing pro-inflammatory microbial profiles and S0 retaining protective functions, providing new insights into gut-kidney axis mechanisms and potential microbiome-targeted therapies for IgAN.
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