Gut microbiota as a predictive tool for outcomes in IgA nephropathy

Immunoglobulin A nephropathy (IgAN) is characterized by the deposition of glycosylation-deficient IgA1 in the glomeruli and has been linked to the gut-kidney axis. This study aimed to determine if baseline differences in gut microbiota could predict therapeutic responses in IgAN patients. We analyzed fecal microbiomes of 55 biopsy-confirmed IgAN patients and followed them for over 6 months. Patients were classified as responders (<i>n</i> = 39) or nonresponders (<i>n</i> = 16) based on remission status. Fecal microbiomes were profiled using 16S rRNA sequencing, revealing significant microbiota differences. Nonresponders had increased <i>Proteobacteria</i> and <i>Firmicutes</i>, with notable enrichment of opportunistic bacteria like <i>Escherichia-Shigella</i> and <i>Pseudomonas</i>. A predictive classifier based on 24 amplicon sequence variants, with <i>Escherichia-Shigella</i> and <i>Pseudomonas</i> as key contributors, showed high accuracy in identifying nonresponders (AUC 0.9103, <i>p</i> &lt; 0.0001). These findings highlight the role of microbial dysbiosis in IgAN progression and treatment response, suggesting that gut microbiota analysis could guide personalized therapy for IgAN. Future studies with larger cohorts are needed to validate these results and explore microbiome-based treatments.