Abstract

Introduction: The gut microbiome appears to be predictive of Parkinson’s disease (PD) with constipation. Chronic constipation frequently manifests prior to motor symptoms and impairs quality of life. An osteopathic manipulative medicine (OMM) sequence used physical exam assessment and manual treatment of neuromusculoskeletal dysfunctions pertinent to constipation in PD for this prospective ABA-design study, IRB-NYITBHS1065. The effects of 4 weekly treatments on the gut microbiome among men and women over 40 years old with chronic constipation and PD were investigated. Severity of PD was rated with the Movement Disorders Society-Unified PD rating scale (UPDRS) in six subjects with constipation. Also, the Bristol stool scale and questionnaires validated for constipation were administered for diagnosis, symptom severity, and quality of life during a 4-week control-period (A), 4-weekly OMM-treatments (B), and 2-weeks no-intervention (A). Biweekly stool samples were assessed for normalized microbiota abundance.

Results: The mean Bristol rating improved from type 2 (± 1) Pre-OMM to 3 (± 1; p = .167; d = 0.677) Post-OMM. Mean constipation severity significantly decreased (p = .010; d = 1.508) Post-OMM. Mean quality of life significantly improved (p = .041; d = 1.072) Post-OMM. The Pre-OMM mean number of families within the phylum Firmicutes decreased by 3 (p = .043; d = 1.177) Post-OMM. There were significant changes in the normalized abundance of phyla Actinobacteria (p = .040; d = 0.845) and Verrucomicrobia (p = .024; d = 0.675) as well as in genus Roseburia (p = .033; d = 1.109), Intestinimonas (p = .035; d = 0.627) and Anaerotruncus (p = .004) Post-OMM.

Conclusion: The gut microbiome shifted among individuals with constipation and PD after four weekly treatments with the OMMsequence. Changes in the gut microbiome Post-OMM were associated with UPDRS results and constipation measures. Clinical trials and studies to develop the gut microbiome into a validated biomarker for PD are necessary to understand the impact of OMM in patients with PD and constipation.

Keywords: Parkinson’s Disease; Constipation; Manual Therapy; Microbiota; Gastrointestinal System; Autonomic Nervous System

References

1. Verbaan D Marinus., et al. “Patient-reported autonomic symptoms in Parkinson's Disease”. Neurology 4 (2007): 333-341.
2. Hou JG and Lai E. “Non-Motor Symptoms of Parkinson's Disease”. International Journal of Gerontology 2 (2007): 53-64.
3. Asahina M., et al. “Autonomic dysfunction in parkinsonian disorders: assessment and pathophysiology”. Journal of Neurology, Neurosurgery, and Psychiatry 6 (2013): 674-680.
4. Del Tredici K and Jost WH. “Gastrointestinal dysfunction in idiopathic Parkinson's disease”. Der Nervenarzt 10 (2012): 1282-1291.
5. Nellesen D., et al. “A systematic review of the economic and humanistic burden of illness in irritable bowel syndrome and chronic constipation”. Journal of Managed Care and Specialty Pharmacy 9 (2013): 755-764.
6. Scheperjans F., et al. “Gut microbiota are related to Parkinson’s disease and clinical phenotype”. Movement Disorders 3 (2015): 350-358.
7. Unger MM., et al. “Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls”. Parkinsonism and Related Disorders (2016): 1e7.
8. Zhu L Liu., et al. “Structural changes in the gut microbiome of constipated patients”. Physiological Genomics (2014).
9. DiGiovanna EL., et al. “An Osteopathic Approach to Diagnosis and Treatment”. Philadelphia, PA: Lippincott Williams and Wilkins (2005).
10. Brugman R., et al. “The effect of osteopathic treatment on chronic constipation-A pilot study”. The International Journal of Osteopathic Medicine 1 (2010): 17-23.
11. Tarsuslu T Bol., et al. “The effects of Osteopathic treatment on constipation with cerebral palsy: a pilot study”. Journal of Manipulative and Physiological Therapeutics 8 (2009): 648-653.
12. Pfeiffer RF. “Gastrointestinal dysfunction in Parkinson's disease”. Current Treatment Options in Neurology 54 (2018): 52.
13. Hemarajata P and Versalovic J. “Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation”. Therapeutic Advances in Gastroenterology 1 (2013): 39-51.
14. Mathers SE., et al. “Constipation and paradoxical puborectalis contraction in anismus and Parkinson's disease: A dystonic phenomenon?” Journal of Neurology, Neurosurgery, and Psychiatry 51 (1988): 1503-1507.
15. Kuijpers HC., et al. “The spastic pelvic floor syndrome large bowel outlet obstruction caused by pelvic floor dysfunction: a radiological study”. The International Journal of Colorectal Disease 1 (1986): 44-48.
16. Vrees MD and Weiss EG. “The evaluation of constipation”. Clinics in Colon and Rectal Surgery 2 (2005): 65-75.
17. Krogh K., et al. “Management of chronic constipation in adults”. United European Gastroenterology Journal: SAGE Journals 4 (2017): 465-472.
18. Baille G., et al. “Review: Ventilatory dysfunction in Parkinson’s disease”. The Journal of Parkinson's Disease 6 (2016): 463-471.
19. Baille G., et al. “Early occurrence of inspiratory muscle weakness in Parkinson's disease”. PLoS ONE1 (2018): e0190400.
20. O'Callaghan A and Walker R. “A review of pulmonary function in Parkinson’s disease”. Journal Parkinsonism Restless Legs Syndrome 8 (2018): 13-23.
21. Coggrave M and Norton C. “Management of faecal incontinence and constipation in adults with central neurological disease”. The Cochrane Database of Systematic Reviews Intervention12 (2013): CD002115.
22. Krogh K., et al. “Management of chronic constipation in adults”. United European Gastroenterology Journal: SAGE Journals 4 (2017): 465-472.
23. Krogh K and Christensen P. “Neurogenic colorectal and pelvic floor dysfunction”. Best Practice and Research: Clinical Gastroenterology 4 (2009): 531-543.
24. De Schryyer AM., et al. “Effects of regular physical activity on defecation pattern in middle-aged patients complaining of chronic constipation”. Scandinavian Journal of Gastroenterology 4 (2005): 422-429.
25. Goldfinger MS., et al. “An osteopathic, non pharmacologic approach to Parkinson’s disease, restless leg syndrome and essential tremor”. Osteopathic Family Physician 6 (2017): 30-38.
26. Simrén M. “Physical activity and the gastrointestinal tract”. European Journal of Gastroenterology and Hepatology 10 (2002): 1053-1056.
27. Davies SC., et al. “Ultrasound quantitation of respiratory organ motion in the upper abdomen”. British Institute of Radiology 803 (1994): 1096-1102.
28. Brandner ED., et al. “Physics contribution abdominal organ motion measures using 4D CT”. International Journal of Radiation Oncology, Biology, Physics 2 (2006): 554-560.
29. Bove A., et al. “Consensus statement AIGO/SICCR: Diagnosis and treatment of chronic constipation and obstructed defecation (part I: Diagnosis)”. World Journal of Gastroenterology 14 (2012): 1555-1564.
30. Izumi K. “The measures to evaluate constipation: a review article”. Gastroenterol Nursing2 (2014): 137-146.
31. Marquis P., et al. “Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire”. Scandinavian Journal of Gastroenterology 40 (2005): 540-551.
32. Riegler G and Esposito I. “Bristol Scale Stool Form. A still valid help in medical practice and clinical research”. Techniques in Coloproctology 3 (2001): 163-164.
33. Lewis SJ and Heaton KW. “Stool form scale as a useful guide to intestinal transit time”. Scandinavian Journal of Gastroenterology 32 (1997): 920-924.
34. Hoehn MM and Yahr MD. “Parkinsonism: onset, progression and mortality”. Neurology5 (1967): 427-442.
35. Nicholas A and Nicholas E. “Atlas of Osteopathic Techniques”. 2^nd Lippincott Williams and Wilkins Wolters Kluwer (2012): 86.
36. Degenhardt BF., et al. “Characterizing adverse events reported immediately after osteopathic manipulative treatment”. The Journal of the American Osteopathic Association 3 (2018): 141-149.
37. Akoglu H. “User's guide to correlation coefficients”. Turkish Journal of Emergency Medicine 18 (2018): 91-93.
38. Willis AD. “Rarefaction, alpha diversity, and statistics”. Frontiers in Microbiology 10 (2019): 2407.
39. Sullivan LM. “Statistical primer for cardiovascular research: Repeated measures”. Circulation AHA 117 (2008): 1238-1243.
40. Hulley SB., et al. “Designing Clinical Research 3^rd Edition”. Wolters Kluwer Health Lippincott Williams, and Wilkins Philadelphia, PA (2007).
41. Thomson H., et al. “Applying the ROBINS-I tool to natural experiments: an example from public health”. Systematic Reviews 15 (2018).
42. Tack J., et al. “Effect of prucalopride on symptoms of chronic constipation”. Neurogastroenterology and Motility 26 (2014): 21-27.
43. Chumpitazi BP., et al. “Bristol Stool Form Scale reliability and agreement decreases when determining Rome III stool form designations”. Neurogastroenterology and Motility 3 (2016): 443-448.
44. Frist WH., et al. “Expanding the use of Real-World Evidence in regulatory and value-based payment decision-making for drugs and biologics”. Bipartisan Policy Center (2019).
45. Trull TJ and Ebner-Priemer UW. “Using experience sampling methods/ecological momentary assessment (ESM/EMA) in clinical assessment and clinical research: Introduction to the special section”. Psychological Assessment 4 (2009): 457-462.