Inflammation has recently been attributed to dysbiosis of the gut microbiome, which has been linked to proteinuria in chronic kidney disease. Since Adriamycin® (ADR) is widely used to induce proteinuria in mouse models, the aim of this study was to explore the potential effect of gut microbiome on this process. Both ADR resistant (C57BL/6) and susceptible (BALB/C) strains were part of the induced nephropathy with ADR injection. BALB/C mice significantly presented increased urinary albumin/creatinine ratio (UACR) with renal lesions in pathology, but C57BL/6 mice were absent from kidney damage. Species and genus level resolution analysis showed a shift in gut microbial profile between BALB/C and C57BL/6 mice. ADR further altered the stool microbiome in BALB/C mice, particularly with enrichment of Odoribacter and depletion of Turicibacter, Marvinbryantia and Rikenella. Moreover, the level of UACR in BALB/C mice was marked related to the abundance of Marvinbryantia, Odoribacter and Turicibacter in stool. Meanwhile, ADR remarkably increased the serum levels of interleukin (IL)-2 in BALB/C mice, but not in C57BL/6 mice. It is suggested that the favorably altered stools as shown in the microbiome might promote the inflammation and proteinuria in ADR-sensitive mice, which provides a new insight on the pathogenicity of chronic kidney disease.
Keywords: Adriamycin; Chronic kidney disease; Gut microbiome; Proteinuria.