Irritable Bowel Syndrome, Parkinson Disease
Conditions
Keywords
Alpha-synuclein, Intestinal permeability, Gut-brain axis, Mucosal ultrastructure, Brain function, Microbiota, Metabolomics
Brief summary
Bowel symptoms like constipation and abdominal pain are characteristic symptoms of irritable bowel syndrome (IBS). The pathogenesis and pathophysiology are not fully understood but subject to intense research, with emphasis on aberrations in the gut-brain axis, low-grade inflammation and gut barrier dysfunction that results in increased permeability and microbial translocation. Many patients with Parkinson's disease (PD) have reported bowel symptoms similar to that in IBS patients decades prior to the diagnosis of PD. Epidemiological studies show a significantly elevated risk of developing PD in IBS patients, though there is no knowledge on a pathogenic connection between these disorders. Recent studies show increased gut permeability and intestinal presence of pathological alpha-synuclein aggregates, the neuropathological hallmark in PD, indicating the involvement of the gut-brain axis. We aim to compare the presence of colonic alpha-synuclein between IBS, PD patients and healthy controls to relate these findings to intestinal permeability, ultrastructural mucosal changes, immune cell interactions, microbiota composition and brain function. This project could identify IBS groups at risk of developing PD and birth the development of early clinical diagnostic methods.
Detailed description
All study participants will give 3 study visits and questionnaires and faecal collection kits will be sent to them before the first visit. Visit 1: Study participants will undergo a sigmoidoscopy during which the researchers will collect 16 biopies. Twelve of the biopsies goes to ussing chamber studies of permeability while the remaining biopsies will be alliqoted for ultrastructural characterisation, alpha-synuclein aggregation assay and immunoflourescence. Blood samples will be drawn from the participants at this visits for metabolomic studies and platelet aggregation potential. In addition, study participants will also bring filled out questionnaires and faecal samples (microbiota analysis). Visit 2: Study participants will undergo a functional magnetic resonance imaging session for analysis of brain function. This visit will last for approximately 1 hour (preparations included). Visit 3: Participants will come in for a final sigmoidoscopy where the biopsies will be collected exclusively for performing the immuno-neurophenotyping of lamina propria lymphocytes.
Interventions
None listed
Sponsors
VHIR
Aston University
Region Örebro County
Örebro University, Sweden
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Patients with Parkinson's disease Inclusion Criteria: 1. Confirmed diagnosis by neurologist 2. Males or females aged 45-85 years 3. Signed informed consent
Exclusion criteria
1. Other confirmed GI diseases (such as inflammatory bowel diseases) 2. Concurrent or recent treatment with antibiotics (\< 12 weeks) 3. Concurrent or recent (\< 4 weeks) use of nutritional supplements or herb products affecting intestinal function or mood (e.g. aloe vera, St. John´s Wort and probiotics/prebiotics). 4. Diagnosis of major psychiatric or somatic disease other than PD. 5. Abuse of alcohol or drugs according to Alcohol Use Disorders Identification Test (AUDIT), and/or clinical judgment. 6. Epilepsy. 7. Cerebral bleeding or history of cerebral bleeding. 8. Pregnancy or breastfeeding (will be asked). 9. Claustrophobia. 10. Smoking or using tobacco including snuff. 11. Dominant left-hand. 12. Inoperated apparatus (e.g., pacemaker). 13. Aneurysm clips in the head. 14. Shunts in the head. 15. Grenade-splinter or metal-splinter in the body (e.g.,eyes). 16. Metal or electrodes in the body (e.g., temp-catheter, aortastent, cochleaimplant). 17. Comprehensive tooth-implants or prothesis. 18. Operated in the head. 19. Operated in the heart. 20. Swallowed a video-capsule. 21. Any other reason the investigator feels the subject is not suitable for participation in the study. Patients with IBS Inclusion Criteria: 1. Fulfilling ROME IV criteria upon recruitment 2. Minimum 5 year of IBS symptoms 3. Males or females aged 18-85 years 4. Signed informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence of alpha-synuclein | Stored samples collected from a one day visit will be continously analysed during the 5 year project | Alpha-synuclein is the hallmark protein of Parkinson's disease and the presence of this protein will be detected with immunoflourescence in colonic tissues |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mucosal ultrastructure: cell activation | Stored samples collected from a one day visit will be continously analysed during the 5 year project | Morphologic quantification of cell size and granule density using Electron microscopy |
| Mucosal ultrastructure: cell-to-cell interaction | Stored samples collected from a one day visit will be continously analysed during the 5 year project | Quantitative measurement of distance between cells to interpolate cell-to-cell interaction using Electron microscopy |
| Microbiota composition | Stored samples collected from a one day visit will be continously analysed during the 5 year project | Analysis of faecal microbiota composition and function (metagenomics) |
| Metabolomics | Stored samples collected from a one day visit will be continously analysed during the 5 year project | Metabolomic analysis of inflammatory markers, sex hormones and enviromental pollutants in blood and faeces |
| Brain function | 1day | Structural and functional alterations in the brain and brainstem using functional magnetic resonance imaging |
| Aggregation potential of alpha-synuclein | Stored samples collected from a one day visit will be continously analysed during the 5 year project | Measure the potential of alpha-synuclein to form aggregates in colonic biopsies |
| Platelet aggregation | 1 day | Platelets will be isolated from blood samples and run on an aggregometer to elcuidate platelet aggregation potential |
| Immunophenotyping | 1 day | Lamina propria lymphocytes will be characterised for their immune-neurophenotype using flow cytometry |
| Intestinal permeability | 1 day | Colonic permeability measured by biopsies mounted in Ussing chambers |
| Irritable bowel syndrome- symptom severity scale (IBS-SSS) | 1 day | This scale evaluates five aspects of IBS during a 10-day period: abdominal pain, distension, stool frequency and consistency and interference with daily life. Each item is scored on a visual analogue scale from 0 to 100 and the sum is the total score. The scale is responsive to treatment and has good validity. |
| Food Frequency Questionnaire (FFQ) | 1 day | The dietary pattern will be assessed through a food frequency questionnaire that has been validated in a Swedish population. The questionnaire includes 174 foods and drinks and estimates the dietary pattern during one year. This is a common way to evaluate eating habits and in this way, evaluation of the microbiota composition in relation to dietary patterns is possible to assess. |
| Hospital Anxiety and Depression Scale (HAD) | 1 day | The Hospital Anxiety and Depression Scale (HADS) was used to evaluate the psychological distress of study participants.This questionnaire consists of 14 items subdivided in two subscales for the assessment of anxiety or depression. The total score is used as a measure of general psychological distress. The minimum score is 0 and the maximum score is 21. A score \> 8 on respective subscales indicates a significant level of anxiety or depression. |
| Perceived Stress Scale (PSS) | 1 day | The perceived stress scale (PSS) consists of 10 items, including a number of direct questions about current levels of experienced stress. The respondent answers how often a certain emotion has been present during the past month. PSS scores are obtained by reversing responses (e.g., 0 = 4, 1 = 3, 2 = 2, 3 = 1 & 4 = 0) to the four positively stated items (items 4, 5, 7, & 8) and then summing across all scale items. Each item is rated on a 5-point scale ranging from never (0) to almost always (4). The questions in this scale ask about the responders feelings and thoughts during the last month. In each case the questionnaire requires the respondent to indicate by circling how often they felt or thought a certain way. |
| MDS Clinical Diagnostic Criteria for Parkinson's Disease | 1 day | The MDS criteria use a two-step process of PD diagnosis. First, parkinsonism is defined (as bradykinesia in combination with either rest tremor, rigidity, or both). Once diagnosed, the criteria then define whether this parkinsonism is attributable to Parkinson's disease. Not scale-based. |
| Hoehn and Yahr scale/stages (Modified scale) | 1 day | The Hoehn and Yahr scale is one of the most commonly and most widely used scale to describe severity in stages 1-5 of Parkinson's disease worldwide. The modified form includes 0.5 increments. |
| Clinical Impression of Severity Index for Parkinson's disease (CISI-PD) | 1 day | The CISI-PD scale provides a clinical judgment on Parkinson's disease (PD) severity based on motor symptoms and complications, cognitive status, and disability. For each component, the score ranges from 0 (normal) to 6 (very severe). A brief definition is attached to each rank, and the sum of these four items yields a global index ranging from 0 to 24 points. |
| Non-Motor Symptoms Questionnaire | 1 day | An instrument to assess wide range of non-motor symptoms based on list of 30 items by answering with: Yes, Don't know, No. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of non-motor symptoms and initiate further investigation. |
| Gastrointestinal Symptoms Rating Scale - Irritable Bowel Syndrome version (GSRS-IBS) | 1 day | The Gastrointestinal Symptoms Rating Scale (GSRS) evaluates gastrointestinal (GI) symptoms based on the 5 domains diarrhoea, constipation, reflux, indigestion and abdominal pain. The symptoms are assessed with 15 items, ranging in scores 1 to 7 depending on their severity. A score of 1 represents no problems and score 7 represents severe problems. The severity of symptoms may be defined as no problems (1 point), mild (1-2 points), moderate (2-4 points), and severe (4-7 points). The scores for each domain was calculated as the mean score of each corresponding item while the mean total GSRS score reflects the general severity of GI symptoms. |
Countries
Sweden
Outcome results
None listed