Gut Virome Characteristics and Network Alterations in IgA Nephropathy

Emerging evidence implicates gut microbiota dysbiosis in the pathogenesis of IgA nephropathy (IgAN), yet the contribution of the gut virome remains unexplored. This study aimed to characterize virome signatures and virus-microbiota interactions in IgAN.

We performed a rigorously matched case-control study including 32 patients with biopsy-proven IgAN and 32 healthy controls. Fecal viral-like particles and bacterial communities were profiled using metagenomic sequencing and full-length 16S ribosomal RNA (rRNA) sequencing. Statistical analysis included diversity, differential abundance, network analysis, and correlation with clinical indices.

IgAN subjects displayed significant reductions in gut virome richness (severe IgAN vs. healthy controls, P = 0.03), with a lower relative abundance of Caudoviricetes in severe IgAN (P = 0.045) and enrichment of Tectiliviricetes in mild disease (P = 0.03). We identified 113 differentially abundant bacteriophage contigs (82 up, 31 down; false discovery rate < 0.05); key predicted hosts shifted toward Bacteroides, Clostridium, and Roseburia in IgAN, whereas Faecalibacterium and Alistipes prevailed in controls. Viral and bacterial alpha diversity correlated in healthy controls but not in IgAN (r = 0.38, P = 0.03 vs. r = 0.04, P = 0.81). IgAN virome encoded more glyco-modifying enzymes (P < 0.05), with strong correlations to estimated glomerular filtration rate (eGFR) (r = 0.65, P = 0.001). Viral and bacterial alpha diversity were significantly correlated with proteinuria and gross hematuria (r = 0.18-0.25, - < 0.05).

This study describes potential alterations in gut virome diversity, bacteriophage composition, bacteriome-virome relationships, and predicted functional profiles in IgAN, suggesting potential relevance of the gut virome to intestinal ecological alterations.