Figure 1.

The etiological mechanism of Parkinson’s disease. Gut microbiota dysbiosis leads to increased intestinal permeability and systemic exposure of bacterial endotoxins, thereby initiating excess α-syn expression and supporting its misfolding to form LBs. The intestinal LBs from ENS will reach the CNS through the vagal nerve and eventually move to and damage the substantia nigra, which will lead to the appearance of the clinical symptoms of PD. The α-syn protein is generally expressed in the CNS with a function of modifying the supply and release of dopamine to regulate neurotransmission in the brain, while, in PD patients’ brains, α-syn protein is overexpressed and forms the LBs will cause dopamine release decreased. Moreover, LBs are the most toxic species in the brain. Mitochondrial dysfunction can be found under pathological conditions. Apoptotic signals are transmitted to the mitochondria, causing the release of Cyto C, which located in the intermembrane of mitochondria. Cyto C activates caspase9, causing protein hydrolysis and eventually leading to neuronal apoptosis. Under normal physiological conditions, neuronal cells have a highly resistant ability to apoptosis. However, when the conditions are pathological, their auto-apoptosis can occur abnormally and cause DA neurons degeneration. Bacteria, including Enterobacteriaceae, Ralstonia, Proteobacteria, etc. are increased in PD stool samples, which will raise the serum lipopolysaccharide (LPS) and other endotoxins concentration. And bacteria like Bacillus spp., Lactobacillus spp., Streptococcus spp. that can produce neurotransmitters such as gamma-aminobutyric acid (GABA), serotonin, and dopamine separately are decreased in PD stool samples. LB, Lewy’s body; CNS, central nervous system; ENS, Enteric nervous system; PD, Parkinson’s disease; Cyto C, Cytochrome C; DA, dopamine.