Intestinal flora imbalance affects the prognosis of Parkinson's disease by regulating the expression of fecal microRNA-146a and GDNF: A Preliminary Study

Abstract

IntroductionThere is mounting evidence showing the association between the gut microbiome and Parkinson’s disease (PD). In this study, we aimed to explore the role of intestinal flora imbalance in the progression of PD and the underlying molecular mechanism involving the regulatory relationship between miR-146a and glial cell line–derived neurotrophic factor (GDNF).Material and methodsA total of 42 PD patients were recruited in this study and grouped according to their prognosis. Real-time PCR, computational analysis and luciferase assay were carried out to explore the role of miR-146a and GDNF in PD patients as well as the regulatory relationship between the expression of miR-146a and GDNF. A rat model was used to study the effect of intestinal flora imbalance by treating the rats with Lactobacillus rhamnosus NCDC17.ResultsA lower count of total lactobaccilus and B. fragilis may predict the progression of PD. GDNF was identified as a virtual target gene of miR-146a, whose expression in fecal, plasma and cerebral tissue samples was significantly reduced in PD patients. In addition, the presence of miR-146a precursors and GDNF siRNA significantly reduced the mRNA and protein levels of GDNF in SH-SY5Y and U251 cells, and the inhibitory effect of miR-146a precursors on GDNF expression was similar to that of GDNF siRNA.ConclusionsTaken together, the findings of this study demonstrated that GDNF is a key factor involved in the prognosis of PD. we suggested that the administration of Lactobacillus rhamnosus NCDC17 promoted the pathogenesis of PD by regulating the expression of miR-146a and GDNF in the brain.