Antibiotic-induced intestinal microbiota depletion can attenuate the acute kidney injury to chronic kidney disease transition via NADPH oxidase 2 and trimethylamine-N-oxide inhibition

Mar 2, 2024Kidney international

Reducing gut bacteria with antibiotics may slow kidney damage progressing from sudden injury to chronic disease by lowering harmful molecules

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Abstract

Plasma trimethylamine N-oxide (TMAO) is associated with a 4.389-fold increased risk for transitioning from acute kidney injury (AKI) to chronic kidney disease (CKD).

  • AIMD reduced TMAO levels in a murine model of AKI-to-CKD transition, leading to decreased apoptosis, inflammation, and fibrosis.
  • NOX2 activation was linked to TMAO-induced fibrosis and oxidative stress in human proximal tubular epithelial cells.
  • Inhibition of NOX2 resulted in reduced pathological changes and oxidative stress in vivo, irrespective of TMAO levels.
  • TMAO is identified as a crucial metabolite in the AKI-to-CKD transition, with NOX2 acting as a key regulator.

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