In recent years, the clinical impact of intestinal microbiota–kidney interaction has been emerging. Experimental evidence highlighted a bidirectional evolutionary correlation between intestinal microbiota and kidney diseases. Nonetheless, acute kidney injury (AKI) is still a global public health concern associated with high morbidity, mortality, healthcare costs, and limited efficient therapy. Several studies on the intestinal microbiome have improved the knowledge and treatment of AKI. Therefore, the present review outlines the concept of the gut–kidney axis and data about intestinal microbiota dysbiosis in AKI to improve the understanding of the mechanisms of the intestinal microbiome on the modification of kidney function and response to kidney injury. We also introduced the future directions and research areas, emphasizing the intervention approaches and recent research advances of intestinal microbiota dysbiosis during AKI, thereby providing a new perspective for future clinical trials.

Emerging evidence suggests that ferroptosis is highly correlated with the pathogenesis of acute kidney injury (AKI). Ferroptosis, an iron-dependent form of cell death, is manifested by a toxic accumulation of lipid peroxides and ultrastructural changes in mitochondria. We herein investigated the effect of Visomitin (SKQ1), a novel mitochondria-targeting antioxidant, on several AKI models in vivo and in vitro. Our results revealed that SKQ1 treatment greatly reversed renal outcomes in cisplatin, ischemia-reperfusion injury (IRI), or folic acid-induced AKI models. These effects were reflected in attenuated levels of renal injury biomarkers, histologic indices of tubular injury, and inflammatory infiltration in the SKQ1-treated groups. Transcriptomics analysis depicted ferroptosis signaling as the most pronounced pathway downregulated after SKQ1 treatment. Consequently, administration of SKQ1 significantly ameliorated lipid peroxide accumulation and inhibited ferroptosis in the kidneys of mice with AKI. In cultured human proximal tubule epithelial cells (HK2), SKQ1 treatment markedly mitigated cisplatin-induced mitochondrial reactive oxygen species (ROS) production, resulting in lower levels of lipid peroxidation and ferroptosis. In conclusion, SKQ1 treatment protected against ischemic- or nephrotoxic-induced AKI by inhibiting ferroptosis in vivo and in vitro. These results could facilitate a broader understanding of the interaction between mitochondrial antioxidants and ferroptotic defense mechanisms, providing a possible therapeutic strategy in AKI.

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