early signs of parkinsons disease in ibs

Conditions: Parkinson Disease; Irritable Bowel Syndrome

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.

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.

Eligibility 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 exclusion criteria: 1. other confirmed gi diseases (such as inflammatory bowel diseases) or pd 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). 3) diagnosis of major psychiatric or somatic disease. 4) abuse of alcohol or drugs according to alcohol use disorders identification test (audit), and/or clinical judgment. 5) epilepsy. 6) cerebral bleeding or history of cerebral bleeding. 7) pregnancy or breastfeeding (will be asked). 8) claustrophobia. 9) smoking or using tobacco including snuff. 10) dominant left-hand. 13) inoperated apparatus (e.g., pacemaker). 14) aneurysm clips in the head. 15) shunts in the head. 16) grenade-splinter or metal-splinter in the body (e.g.,eyes). 17) metal or electrodes in the body (e.g., temp-catheter, aortastent, cochleaimplant). 18) comprehensive tooth-implants or prothesis. 19) operated in the head. 20) operated in the heart. 21) swallowed a video-capsule. 25) any other reason the investigator feels the subject is not suitable for participation in the study. healthy controls: inclusions criteria: 1. males or females aged 18-85 2. signed informed consent exclusion criteria: 1. concurrent or recent treatment with drugs affecting intestinal microbiota, function or mood, e.g., antidepressants (\< 12 weeks), antibiotics (\< 12 weeks) 2. no on going gi symptoms 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. 5. abuse of alcohol or drugs according to alcohol use disorders identification test (audit), and/or clinical judgment. 6. recent (\< 4 weeks) intake of proton pump inhibitors, ppi (e.g., omeprazol). 7. epilepsy. 8. cerebral bleeding or history of cerebral bleeding. 9. pregnancy or breastfeeding (will be asked). 10. claustrophobia. 11. smoking or using tobacco including snuff. 12. dominant left-hand. 13. inoperated apparatus (e.g., pacemaker). 14. aneurysm clips in the head. 15. shunts in the head. 16. grenade-splinter or metal-splinter in the body (e.g., eyes). 17. metal or electrodes in the body (e.g., temp-catheter, aortastent, cochleaimplant). 18. comprehensive tooth-implants or prothesis. 19. operated in the head. 20. operated in the heart. 21. swallowed a video-capsule. 22. regular intake of anti-inflammatory medication (including nsaids). 23. any other reason the investigator feels the subject is not suitable for participation in the study.

Keywords: alpha-synuclein intestinal permeability gut-brain axis mucosal ultrastructure brain function microbiota metabolomics