Targeted release of budesonide modulates key gut microbial abnormalities in immunoglobulin A nephropathy.

BACKGROUND: Gut microbiota dysbiosis has been implicated in the pathogenesis of immunoglobulin A nephropathy (IgAN), but whether different therapies are associated with distinct microbial profiles remains unclear. We aimed to investigate gut microbiota changes in IgAN patients receiving targeted-release budesonide (Nefecon), systemic glucocorticoids, or non-immunosuppressive therapy. METHODS: In this comparative study, 24 biopsy-proven IgAN patients were divided into four groups: newly diagnosed untreated patients (n = 8), patients in remission after non-immunosuppressive therapy (n = 6), patients treated with Nefecon for at least 3 months (n = 5), and patients treated with systemic glucocorticoids for at least 3 months (n = 5). Nine healthy volunteers served as controls. Fecal microbiota was profiled by 16S rRNA gene sequencing, and community diversity, taxonomic composition, and associations with clinical/pathological parameters were analyzed. RESULTS: Newly diagnosed IgAN patients exhibited reduced alpha diversity and a distinct beta diversity profile compared with healthy controls. The Nefecon group exhibited a microbial community structure more similar to that of controls than the newly diagnosed or remission groups. Several bacterial genera were significantly altered in newly diagnosed IgAN patients, including taxa enriched relative to both controls and the Nefecon group. Furthermore, microbiota composition correlated with renal pathological features, particularly segmental glomerulosclerosis and sclerosis ratio. CONCLUSION: Although limited by a small sample size, these findings suggest that targeted mucosal immunomodulation with Nefecon may partially restore gut microbial homeostasis in IgAN patients, providing new insight into the gut-kidney axis and the microbiota-related effects of therapy.