Altered gut microbiome promotes proteinuria in mice induced by Adriamycin

Area of Science:

• Microbiology
• Nephrology
• Immunology

Background:

• Gut dysbiosis is increasingly implicated in inflammation and chronic kidney disease (CKD) pathogenesis.
• Proteinuria is a hallmark of CKD, and Adriamycin (ADR) is a common experimental model inducer.
• The role of the gut microbiome in ADR-induced nephropathy remains to be fully elucidated.

Purpose of the Study:

• To investigate the influence of the gut microbiome on Adriamycin-induced proteinuria and kidney damage.
• To compare the effects of ADR on gut microbial composition in ADR-resistant and ADR-susceptible mouse strains.

Main Methods:

• Utilized C57BL/6 (ADR-resistant) and BALB/C (ADR-susceptible) mouse models.
• Administered Adriamycin (ADR) to induce nephropathy and analyzed urinary albumin/creatinine ratio (UACR).
• Performed species and genus level analysis of stool microbiome composition and measured serum interleukin-2 (IL-2) levels.

Main Results:

• BALB/C mice developed significant proteinuria and renal lesions, unlike C57BL/6 mice.
• ADR administration altered the gut microbiome in BALB/C mice, enriching Odoribacter and depleting Turicibacter, Marvinbryantia, and Rikenella.
• Proteinuria levels (UACR) in BALB/C mice correlated with the abundance of Marvinbryantia, Odoribacter, and Turicibacter.
• ADR increased serum IL-2 levels in BALB/C mice but not in C57BL/6 mice.

Conclusions:

• Gut microbiome dysbiosis, characterized by specific bacterial shifts, contributes to Adriamycin-induced inflammation and proteinuria in susceptible mice.
• These findings offer novel insights into the mechanisms underlying CKD pathogenicity.
• Targeting the gut microbiome may represent a potential therapeutic strategy for managing proteinuric kidney diseases.