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Abstract: SA-PO0868

Phocaeicola dorei-Derived Outer Membrane Vesicles Protect Against Diabetic Kidney Disease by Activating Autophagy

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1500 Health Maintenance, Nutrition, and Metabolism

Authors

  • Li, Huangmin, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
  • Zhao, Zhanzheng, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
  • Dong, Zheng, Augusta University Medical College of Georgia, Augusta, Georgia, United States
Background

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) requiring effective therapeutics. Emerging evidence suggests an important role of the gut-kidney axis in DKD pathogenesis. Phocaeicola dorei has metabolic regulatory, immunomodulatory, and anti-inflammatory potential in the gut, but its role in DKD remains unclear. We hypothesized that P. dorei-derived outer membrane vesicles (OMVs) modulate DKD.

Methods

Fecal metagenomic profiling was performed in patients with biopsy-confirmed DKD (n=10) and patients with diabetes (DM, n=13), followed by correlation analysis with clinical renal function parameters. The effects of live P. dorei and OMVs were validated in STZ-induced DKD mice. OMVs were isolated by ultracentrifugation and characterized by TEM and NTA. DiR-labeled OMVs were tracked by IVIS in vivo and confocal microscopy in vitro. The protective and regulatory roles of OMVs in renal tubular epithelial cells were further examined using molecular and cellular assays.

Results

P. dorei was relatively abundant and exhibited the most significant decrease in DKD. Its abundance was negatively correlated with BUN and SCr and positively correlated with eGFR, suggesting an association with preserved renal function. In STZ-induced DKD mice, oral gavage of live P. dorei ameliorated renal injury, with reduced inflammation, fibrosis, and histological damage. Notably, oral gavage of OMVs showed similar protective effects. In vivo fluorescence imaging showed that DiR-labeled OMVs reached the kidney, and confocal microscopy further demonstrated their internalization by tubular cells. In high glucose-treated RPTC cells, OMVs improved cell viability, reduced p62 accumulation, partially restored LC3B expression, and reversed high glucose-induced alterations in AMPK phosphorylation.

Conclusion

P. dorei-derived OMVs may attenuate renal tubular injury in DKD by modulating the AMPK-autophagy axis, highlighting a potential microbiota-derived therapeutic strategy for DKD.