Increased Gut Permeability to Lipopolysaccharides (LPS) in Parkinson's Disease

• Total urine sugar per 24 hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  Subjects consume a mixture of sugars (lactulose, sucrose), then collect urine for 24 hours. Sugar concentrations in the urine are assayed by gas chromatography.
  
  
• LH-PCR fingerprint analysis [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  Total genomic DNA will be extracted from colonic mucosa biopsy specimens and lumenal samples, and will be amplified by PCR using bacterial primers. PCR products will be separated and analyzed for amplicon length heterogeneity.
  
  
• Blood endotoxin and cytokine levels [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  Blood endotoxin and cytokine levels
  
  
• Histopathology and immunohistochemistry of colonic mucosa [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  A portion of the colonic tissue will be studied with histopathology and immunohistochemistry techniques for alpha-synuclein pathology, cytokines and inflammatory markers.
  
  

Clinical and pathological data suggest Parkinson's disease (PD) may result from an inflammatory process beginning in the intestinal wall that initiates alpha-synuclein aggregation, which then spreads from neuron to neuron, reaching the central nervous system. Bacteria living within the intestinal tract produce lipopolysaccharide endotoxin, a toxin known to induce parkinsonism in animal models. We hypothesize that exposure to LPS, either from excessive production or excessive absorption may be the cause of this inflammation. This study aims to: (1) describe differences in the population of gut bacteria in PD compared to control subjects; (2) assess leakiness of the gut wall by differential absorption of non-absorbable sugars; (3) measure plasma levels of endotoxin and inflammation; and (4) study characteristic PD pathology and evidence of inflammation in biopsy samples of the colon obtained by sigmoidoscopy.