Rifaximin as a Potential Treatment for IgA Nephropathy in a Humanized Mice Model.

ABSTRACT: IgA Nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by the mesangial deposition of abnormally glycosylated IgA1 (Gd-IgA). The production of Gd-IgA occurs in mucose-associated lymphoid tissue (MALT). The microbiota plays a role in MALT modulation. Rifaximin (NORMIX^®), a non-absorbable oral antibiotic, induces positive modulation of the gut microbiota, favoring the growth of bacteria beneficial to the host. Here, we evaluate the effect of rifaximin on a humanized mice model of IgAN (α1^KI-CD89^Tg). Methods: The α1^KI-CD89^Tg mice were treated by the vehicle (olive oil) or rifaximin (NORMIX^®). Serum levels of hIgA, hIgA1-sCD89, and mIgG-hIgA1 immune complexes were determined. Glomerular hIgA1 deposit and CD11b+ cells recruitment were revealed using confocal microscopy. Furthermore, the mRNA of the B-Cell Activating Factor (BAFF), polymeric immunoglobulin receptor (pIgR), and Tumor Necrosing Factor-α (TNF-α) in gut samples were detected by qPCR. Results: Rifaximin treatment decreased the urinary protein-to-creatinine ratio, serum levels of hIgA1-sCD89 and mIgG-hIgA1 complexes, hIgA1 glomerular deposition, and CD11b+ cell infiltration. Moreover, rifaximin treatment decreased significantly BAFF, pIgR, and TNF-α mRNA expression. Conclusions: Rifaximin decreased the IgAN symptoms observed in α1^KI-CD89^Tg mice, suggesting a possible role for it in the treatment of the disease.

SUBMITTER: Di Leo V 

PROVIDER: S-EPMC8072762 | biostudies-literature |

REPOSITORIES: biostudies-literature