Abstract: TH-OR028
The Microbiota Is a Central Determinant in IgA Nephropathy as Its Modulation Prevents Disease Development
Session Information
- Clinical Glomerular Disorders: Trials, Treatment, Case Findings
November 02, 2017 | Location: Room 292, Morial Convention Center
Abstract Time: 05:54 PM - 06:06 PM
Category: Glomerular
- 1001 Glomerular: Basic/Experimental Immunology and Inflammation
Authors
- Chemouny, Jonathan M., AP-HP, Hopital Bichat, Paris, France
- Lepage, Patricia, INRA, Jouy-en-Josas, France
- Gleeson, Patrick J, INSERM U1149 & ELR8252 CNRS, Paris, France
- Abbad, Lilia, INSERM U1149 & ELR8252 CNRS, Paris, France
- Jamin, Agnes, INSERM U1149 & ELR8252 CNRS, Paris, France
- Daugas, Eric, AP-HP, Hopital Bichat, Paris, France
- Vrtovsnik, Francois, AP-HP, Hopital Bichat, Paris, France
- Ben mkaddem, Sanae, INSERM U1149 & ELR8252 CNRS, Paris, France
- Berthelot, Laureline, INSERM U1149 & ELR8252 CNRS, Paris, France
- Leclerc, Marion, INRA, Jouy-en-Josas, France
- Monteiro, Renato C., AP-HP, Hopital Bichat, Paris, France
Background
IgA nephropathy (IgAN) is associated with microbiota dysbiosis when compared to healthy individuals (De Angelis et al. PLoS One 2014). Here, we studied the composition of fecal microbiota of IgAN patients compared with non-IgAN glomerular disease (non IgAN-GD). An IgAN mouse model (α1KI-CD89Tg) was used to study the effect of gut microbiota modulation in disease development.
Methods
We collected feces from patients with IgAN and non-IgAN-GD. Fecal microbiota compositions were studied through 16S rRNA pyrosequencing. For the experimental part of the study, 31 four-week old male α1KI-CD89Tg mice were fed an antibiotic mix (ATB) or vehicle twice a week for 8 weeks. Urine samples were collected before the first administration. At the end of experiments, urine, blood samples and kidneys were collected. Proteinuria and creatininuria were measured.
Results
IgAN and non-IgA-GN patients showed significant differences in proportions of the main phylum Firmicutes (p=0.020) and in Lentispherae (p=0.019). As the data suggest an IgAN-linked dysbiosis, we targeted the gut microbiota in a mouse model of IgAN to modulate disease expression. As expected total bacterial load was significantly lesser in the ATB group (p<0.001). Protein/creatinine ratio (PCR) did not rise over the course of 12 weeks in the ATB group (p=0.436) whereas there was a significant increase (p<0.001) in the PCR in the vehicle control group. Markedly less mesangial IgA1 deposits was seen in the ATB group. While no differences were seen in serum human IgA1 levels in the mice, there were significantly fewer lymphoid follicles in Peyer’s patches (PP) among ATB treated as compared to vehicle group.
Conclusion
Our data suggest the gut dysbiosis in IgAN patients may be independent of the effect of CKD. Moreover, gut commensal bacteria may have a pathogenic role in IgAN as gut microbiota modulation through the administration of antibiotics prevented disease development in mice. Finally, nephrotoxic IgA1 may originates from the gut mucosa, as despite the presence of PP alterations in ATB group, serum IgA1 levels remained unaffected.
Funding
- Government Support - Non-U.S.