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

Study Overview
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Brief Summary
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The gut may be a portal of entry for agents that cause or contribute to the causes of Parkinson's disease (PD). The investigators are studying changes in the normal population of gut flora and in intestinal permeability and their associations with early PD.

Detailed Description
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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.

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

Conditions
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Parkinson's Disease, Multiple System Atrophy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria--Parkinson's disease: Clinically diagnosed Parkinson's disease Hoehn & Yahr stage 1-2.5 No symptomatic treatment of Parkinson's disease symptoms Inclusion Criteria--Multiple System Atrophy Clinically diagnosed Multiple System Atrophy. Inclusion Criteria--Control subjects: No diagnosis of Parkinson's disease and no signs of Parkinson's disease on screening neurological examination Exclusion Criteria: Secondary or atypical parkinsonism other than Multiple System Atrophy Occupation or medical treatment known to influence intestinal flora Organic gastrointestinal disease other than hiatal hernia or hemorrhoids; history of gastrointestinal surgery other than remote appendectomy or cholecystectomy. Acute or chronic medical illness that would confound study results. Coagulopathy or use of anticoagulant medications (including aspirin). Chronic use of diuretics

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Subjects with Parkinson's disease<br>Male and female subjects with clinically diagnosed Parkinson's disease, Stage I-IV. | |
| Control subjects<br>Age- and gender-matched subjects who do not have Parkinson's disease | |
| Multiple system atrophy.<br>Men and women with clinically diagnosed multiple system atrophy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total urine sugar per 24 hours | Subjects consume a mixture of sugars (lactulose, sucrose), then collect urine for 24 hours. Sugar concentrations in the urine are assayed by gas chromatography. | 24 hours | 
| LH-PCR fingerprint analysis | 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. | 24 hours | 
| Blood endotoxin and cytokine levels | Blood endotoxin and cytokine levels | 24 hours | 
| Histopathology and immunohistochemistry of colonic mucosa | A portion of the colonic tissue will be studied with histopathology and immunohistochemistry techniques for alpha-synuclein pathology, cytokines and inflammatory markers. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lipopolysaccharides, etiology, inflammation, colonic bacteria, intestinal permeability