Targeted-release budesonide (Nefecon) may partially restore gut microbial homeostasis in IgAN patients, with the Nefecon group exhibiting a microbial community structure more similar to healthy controls than newly diagnosed or remission groups.
Key Findings
Results
Newly diagnosed IgAN patients exhibited reduced alpha diversity and a distinct beta diversity profile compared with healthy controls.
24 biopsy-proven IgAN patients were divided into four groups: newly diagnosed untreated (n=8), remission after non-immunosuppressive therapy (n=6), Nefecon-treated for at least 3 months (n=5), and systemic glucocorticoid-treated for at least 3 months (n=5)
Nine healthy volunteers served as controls
Fecal microbiota was profiled by 16S rRNA gene sequencing
Both community diversity (alpha diversity) and overall community composition (beta diversity) were significantly different in newly diagnosed IgAN patients relative to healthy controls
Results
The Nefecon group exhibited a microbial community structure more similar to healthy controls than the newly diagnosed or remission groups.
Patients treated with Nefecon for at least 3 months were compared against newly diagnosed, remission, systemic glucocorticoid, and healthy control groups
Beta diversity analysis showed the Nefecon group's microbial profile clustered closer to healthy controls
This pattern was not observed in the non-immunosuppressive remission group, suggesting treatment-specific rather than disease-remission-driven microbial shifts
The systemic glucocorticoid group did not show the same degree of similarity to controls as the Nefecon group
Results
Several bacterial genera were significantly altered in newly diagnosed IgAN patients, including taxa enriched relative to both healthy controls and the Nefecon group.
Taxonomic composition analysis identified specific genera differentially abundant in newly diagnosed IgAN patients compared to healthy controls
Some of these enriched taxa in newly diagnosed patients were also reduced in the Nefecon group relative to the newly diagnosed group
16S rRNA gene sequencing was used to identify these taxonomic differences
The direction and identity of specific genera are consistent with previously reported gut dysbiosis patterns in IgAN
Results
Gut microbiota composition correlated with renal pathological features, particularly segmental glomerulosclerosis and sclerosis ratio.
Associations between microbiota composition and clinical/pathological parameters were analyzed
Segmental glomerulosclerosis and sclerosis ratio were the pathological features most notably associated with microbial composition
These correlations suggest a potential link between gut dysbiosis and structural kidney damage in IgAN
The analysis was conducted across all 24 IgAN patients
Discussion
Targeted mucosal immunomodulation with Nefecon may partially restore gut microbial homeostasis in IgAN patients, providing insight into the gut-kidney axis.
The study compared targeted-release budesonide (Nefecon), systemic glucocorticoids, and non-immunosuppressive therapy in terms of associated gut microbial profiles
Nefecon acts via targeted mucosal immunomodulation at the gut level, which may explain its differential effect on microbiota compared to systemic glucocorticoids
Authors note the study is limited by a small sample size (total n=33 including controls)
Findings are described as suggesting rather than confirming a causal relationship between Nefecon and microbial restoration
What This Means
This research suggests that the gut microbiome — the community of bacteria living in the intestines — is disrupted in patients with IgA nephropathy (IgAN), a kidney disease caused by abnormal immune protein deposits. The researchers compared gut bacteria in four groups of IgAN patients (newly diagnosed, in remission with basic therapy, treated with a targeted gut-acting steroid called Nefecon, and treated with standard systemic steroids) as well as healthy volunteers. They found that newly diagnosed IgAN patients had less diverse gut bacterial communities and a distinctly different bacterial composition compared to healthy people, consistent with the idea that gut health may play a role in IgAN.
Importantly, patients treated with Nefecon — a form of the steroid budesonide that is designed to release specifically in the gut rather than throughout the body — had a bacterial community profile that more closely resembled healthy controls than patients who were newly diagnosed or in remission after basic therapy. This was not seen to the same degree in patients taking systemic steroids, suggesting the specific location of drug action in the gut may matter for microbial effects. The researchers also found that certain features of kidney damage visible under the microscope were linked to specific patterns of gut bacteria, further supporting the concept of a gut-kidney connection in this disease.
This research suggests that treating IgAN with a gut-targeted approach like Nefecon may do more than just suppress immune activity — it may also help normalize the gut bacterial environment that is thought to contribute to the disease. However, the study included only 24 IgAN patients and 9 healthy controls, so these findings should be considered preliminary. Larger studies will be needed to confirm whether restoring gut microbial balance is a meaningful part of how Nefecon benefits patients with IgAN.
Mao X, Shang D, Chang S, Yang H, Lai L. (2026). Targeted release of budesonide modulates key gut microbial abnormalities in immunoglobulin A nephropathy.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1856526