Background
The intestinal microbiota affects the inflammatory status of the host and the prognosis of chronic diseases. However, it is not clear whether acute kidney injury (AKI) affects the gut microbiota. Calcitriol (Cal) is the most active form of vitamin D and has anti-inflammatory and antioxidant effects.
Methods and Results
In this study, we determined the close interaction between AKI and the intestinal microbiota and the efficacy and mechanism of high-dose Cal as an intestinal protective agent in AKI rats with renal ischemia–reperfusion injury. 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-1and Occludin), Cal significantly prevented the destruction of the intestinal barrier in AKI. In addition, Cal pretreatment reduced the levels of intestinal IL-1β, IL-6 and TNF-α, downregulated the transcription of a series of inflammatory signaling molecules, and as well as the expression of KIM-1 and IL-6 in the kidney. 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 TLR4-NF-κB signaling.
Conclusions
High-dose Cal may play a protective role in AKI by regulating TLR4-related signaling pathways and the intestinal microbiota. This study demonstrates the renal effects of Cal and its potential therapeutic mechanism and provides new insights for the treatment of AKI.