Clostridium butyricum Inhibits the Inflammation in Children with Primary Nephrotic Syndrome by Regulating Th17 / Tregs Balance via Gut-Kidney Axis

Abstract

Background Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C.butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C.butyricum on PNS inflammation through the gut-kidney axis. Methods BALB/c mice were randomly divided into 4 groups: normal control group (CON), C.butyricum control group (CON + C.butyricum), PNS model group (PNS) and PNS with C.butyricum group (PNS + C.butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C.butyricum or normal saline for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated. Results Since the successfully modelling of the PNS, the 24h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN),urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C.butyricum treatment. The crucial Th17-Tregs axis in PNS inflammation also was proved to be effectively regulated by C.butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C.butyricum could regulate the composition of intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C.butyricum treatment increased contents of acetic acid, propionic acid, butyric acid in feces and acetic acid, valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota and associated metabolic SCFAs in gut-kidney axis. Conclusion C.butyricum regulates Th17 / Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a novel, inexpensive, and safe therapeutic reagent for the control of the disease.