Study Rationale: Studies show that the intestinal environment can affect the activity of the nervous system, and inflammation in the gut could contribute to the brain changes associated with Parkinson’s disease (PD). The cellular structures that separate the interior of the intestine from the rest of the body may be “leaky” in PD, contributing to abnormalities in gut-brain communication. Changes in the composition of the bacteria that inhabit the colon — the microbiome — may further disrupt the gut barrier and lead to intestinal inflammation. This project will explore intestinal inflammation, gut-barrier integrity, and the microbiome in PD.
Hypothesis: We hypothesize that we will find increased intestinal inflammation, accompanied by a loss of gut-barrier function, in people with PD. Further, we hypothesize that these changes will be more severe in individuals with more advanced PD.
Study Design: In this project, we will use colon biopsy samples from 80 individuals, with and without PD, collected as part of the Systemic Synuclein Sampling study (S4). Samples of colon tissue will be examined for markers of immune cells and proteins that are part of the gut barrier. Analysis of these markers will determine whether intestinal inflammation and a loss of barrier integrity are associated with PD—and whether these changes are more pronounced in individuals with advanced PD. We will also test different methods for characterizing the microbiome of colon samples obtained from autopsies.
Impact on Diagnosis/Treatment of Parkinson’s disease: This work will further our understanding of inflammation, gut barrier integrity, and the microbiome in PD. Our findings could translate into treatments that reduce PD risk or severity by targeting inflammation and microbial imbalances.
Next Steps for Development: In future work, we will relate measures of colon inflammation, gut barrier integrity, and microbiome profile to measures of inflammation in the blood and cerebrospinal fluid (using samples also collected in the S4).