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

IgAN-S1 patients had enriched Firmicutes and Patescibacteria at the phylum level compared to IgAN-S0 patients.

• The study enrolled 12 IgAN-S0 (without segmental sclerosis) and 19 IgAN-S1 (with segmental sclerosis) patients.
• 16S rRNA gene sequencing was performed on fecal samples to analyze gut microbiota composition.
• Firmicutes and Patescibacteria were enriched in S1 patients.
• S0 patients had more Proteobacteria, Campylobacterota, and Desulfobacterota at the phylum level.

LEfSe analysis identified distinct bacterial biomarkers differentiating IgAN-S1 from IgAN-S0 patients.

• Subdoligranulum and unclassified_Erysipelotrichaceae_UCG-003 were identified as S1-specific biomarkers (P<0.05).
• Phascolarctobacterium, Streptococcus_parasanguinis, and Proteobacteria were identified as S0-specific biomarkers (P<0.05).
• Analysis was performed using Linear discriminant analysis Effect Size (LEfSe) methodology.
• These biomarkers distinguished the two patient groups based on Oxford classification S lesion status.

Functional prediction revealed that IgAN-S1 gut microbiota was enriched in pro-inflammatory metabolic pathways.

• S1 patients showed enrichment in endoplasmic reticulum stress pathways.
• Secondary bile acid biosynthesis pathways were also enriched in S1 patients.
• These functional profiles were characterized as pro-inflammatory in nature.
• Functional predictions were derived from 16S rRNA gene sequencing data analysis.

IgAN-S0 patients retained activated protective functional pathways in their gut microbiome compared to S1 patients.

• S0 patients had activated cytochrome P450 drug metabolism pathways.
• The ubiquitin system pathway was also activated in S0 patients.
• These pathways were characterized as protective functions absent or reduced in S1 patients.
• The functional differences suggest the gut microbiome may contribute to differential renal outcomes between S0 and S1 patients.

Segmental glomerulosclerosis (S1 lesion in Oxford classification) is an independent predictor of poor renal prognosis in IgAN, with 20%-40% of IgAN-S1 patients progressing to end-stage renal disease.

• IgAN is described as a common immune-complex-mediated glomerulonephritis.
• The S lesion refers to segmental glomerulosclerosis as classified by the Oxford classification system.
• 20%-40% of IgAN-S1 patients progress to end-stage renal disease.
• The pathogenesis of S1 lesion development was noted as unclear prior to this study.