Gut microbial dysbiosis aggravated Parkinson-like pathology induced by MPTP/probenecid

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder, characterized by resting tremor, bradykinesia, rigidity and postural instability. Recent studies have proved that gut microbiota (GM) dysbiosis exists in PD patients. However, the causal relationship between gut microbial dysbiosis and pathogenesis of PD remains unexplored. Here, using MPTP/probenecid-induced PD mouse model and an antibiotic cocktail (ABX)-induced pseudo-germ-free status, we observed that GM diversity and abundance significantly decreased in feces of ABX-treated PD mice by 16S rRNA sequencing. Remarkably, gut microbial dysbiosis induced by ABX aggravated GI dysfunction and motor deficits in PD mice. Moreover, ABX treatment caused more severe inflammation, and dopaminergic (DAergic) neuronal loss in both the gut and brain. Further study showed that fecal microbiota transplantation (FMT) corrected gut microbial dysbiosis, along with increased short-chain fatty acids (SCFAs). Additionally, GI and motor dysfunctions were improved, peripheral and central inflammation were also attenuated when PD mice were treated with FMT. These findings revealed that gut microbial dysbiosis could aggravate PD pathological damages, and highlighted that gut microbial dysbiosis might be an important factor that impacts PD pathogenesis through the microbiota-gut-brain axis.