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Intestinal Microbiota, Permeability and Alpha-synclein Aggregation in Parkinson's Disease

Changes in the intestinal system may occur early in the development of Parkinson’s disease. The intestinal system is important to (1) maintain normal “healthy” bacteria; and (2) protect against absorption of toxins. This study will (1) identify changes in the types of bacteria living in the intestines, (2) study “leakiness” of the intestine, and (3) look for characteristic degenerative changes in the nerve cells of the intestinal wall in Parkinson’s disease.

Project Description:
We will recruit 50 subjects: 30 with Parkinson’s disease, 10 with multiple system atrophy, and 10 healthy controls. We will take small samples of intestinal tissue (biopsy) using a flexible scope inserted about 8 inches into the rectum. The procedure does not require a “prep.” These samples will be used to identify intestinal bacteria and to study characteristic microscopic changes in nerve cells in the intestinal wall. “Leakiness” will be studied by having the subjects swallow a mixture of sugars (liquid and capsules), then collect their urine for 24 hours. We will measure how much of the sugar is excreted into the urine.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If abnormalities in the intestinal bacteria or leakiness of the intestines are found to be important in Parkinson’s disease, it may lead to new treatments focused on changing bacterial populations or reducing intestinal leakiness. A better understanding of the changes in the nerve cells in the intestinal wall may lead to more accurate diagnostic tests for Parkinson’s disease.

Anticipated Outcome:
We hope to find that subjects with Parkinson’s disease have abnormal bacteria living in their intestines, and to identify which bacteria are important in the disease. We hope to find “leakier” intestines in Parkinson’s disease subjects, that may promote absorption of toxins. Alpha-synuclein protein accumulation in brain cells is the characteristic feature of Parkinson’s disease, and we hope to find this protein in nerve cells of the intestinal wall.

Final Outcome

The purpose of this study was to explore the intestinal environment in Parkinson’s disease (PD). We studied patients with PD, Multiple system atrophy (MSA) and health controls. We found that we could detect alpha-synuclein, the marker protein that accumulates in the brain cells in PD, in nerve cells in the lower intestine in most PD subjects (64%).  Subjects with MSA rarely showed this protein in their intestinal nerve cells (17%).  Healthy controls who were not relatives or spouses of PD subjects showed intestinal alpha-synuclein only 10% of the time.  However, 50% of siblings and spouses of PD subjects showed alpha-synuclein in the intestine. 

PD subjects had increased intestinal permeability (“gut leakiness”) compared to healthy subjects.  Subjects with MSA also had increased intestinal permeability.  Spouses and siblings of PD subjects also had increased intestinal permeability.

Studies of the types and diversity of bacteria living within the lower intestine showed that subjects with PD may carry a different population of bacteria in their intestines.  We believe that these finding illustrate that abnormalities in intestinal permeability (“leakiness”) and differences in the types and diversity of intestinal bacteria are common in PD.  Alpha-synuclein, the marker protein in PD can be detected in tissue samples taken from the lower intestine.  Additional studies are needed to determine whether these abnormalities are important in the cause or progression of PD and whether targeting these abnormalities might influence the course of the illness.


  • Kathleen M. Shannon, MD, FAAN, FANA

    Madison, WI United States

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