Calcitriol Alleviates AKI Via Inhibiting Intestinal Inflammation and Restoring Intestinal Microbiota

Abstract

Abstract Background：The intestinal microbiota affects the inflammatory status of the host and the prognosis of diseases. AKI can lead to microinflammation of intestinal tract and changes of intestinal flora. Calcitriol (Cal) has a protective effect on the intestine. Methods and Results：In the AKI rat model, intestinal infiltration of inflammatory cells and the deterioration of renal function were significantly alleviated by Cal pretreatment. By increasing the levels of Zonula Occludens-1(ZO-1 and Occludin), Cal significantly prevented the destruction of the intestinal barrier in AKI. In AKI rats, Cal decreased the concentration of Proteobacteria and enhanced the linear discriminant (LDA) score of beneficial bacteria (such as Lactobacillus). Cal increased the expression of butyric acid among intestinal metabolites. Cal supplementation decreased serum LPS levels and downstream HMGB1-MYD88-NF-κB-p65 signaling. Conclusions：High-dose Cal may play a protective role in AKI by regulating HMGB1-MYD88-NF-κB-p65 signaling pathways and the intestinal microbiota in rats. This study demonstrates the renal effects of Cal. The experiment revealed a close interaction between the kidney and the intestine. It provides new insights for the treatment of AKI.