Quantitative increase in short-chain fatty acids, especially butyrate protects kidney from ischemia/reperfusion injury

Short-chain fatty acids (SCFAs), the end products of fermentation carried out by the intestinal microbiota, were demonstrated to produce anti-oxidant and anti-inflammatory effects. Butyrate, part of the SCFAs, also shows the same effect. Renal ischemia/reperfusion (I/R) injury commonly occurs in renal transplantation and is often accompanied by oxidative stresses and inflammatory responses. In this study, we explore butyrate effect on renal I/R injury and SCFAs changes in renal transplant. Male Sprague-Dawley rats were pretreated with butyrate as research, and underwent the surgery of renal ischemia for 45 min followed by reperfusion. 90 rats were randomly divided into 3 groups (n=30 each group): (1) sham-operated group; (2) butyrate-treated group; (3) control group. The samples of blood and renal were collected immediately for further studies. Thirty-two patients were enrolled to investigate the levels of SCFAs after the renal transplantation. Rats model showed that butyrate treatments significantly enhanced the function and structure of kidney, as evidenced by the lower serum creatinine levels and less pathological damages of renal tissue. With the recovery of renal function after renal transplantation, SCFAs increased, which were negatively correlated with creatinine. Butyrate expressed like SCFAs. In this study, we demonstrated that butyrate increased with the recovery of renal function after renal transplantation. Most importantly, butyrate treatments alleviated the renal damages caused by I/R via the upregulation of intracellular oxidant stress and inflammations.