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. Acute kidney injury (AKI) can lead to microinflammation of intestinal tract and changes of intestinal microbiota. 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 Lipopolysaccharide (LPS) levels and downstream LPS-induced activation of the NF-κB signaling pathways. Conclusions High-dose CAL may partly play a protective role in AKI by maintaining intestinal integrity. This mechanism is achieved by inhibiting intestinal LPS-activated TLR4/MyD88/NF‐κB signaling pathway and restoring intestinal microbiota in AKI rats. The experiment revealed a close interaction between the intestine and the kidney. It provides new insights to the role of the intestine in the development of AKI.