NAME OF RESEARCHER
Rosalind Tucker
NAME OF SUPERVISOR
Prof David Taylor, Dr R John Dobbs
PROJECT TITLE
The gut in Parkinson’s. Helicobacter species and constipation as drivers of disease and the link between Parkinson’s Disease & Livestock Farming.
CLINICAL ACADEMIC GROUP
Pharmaceutic Science
START & FINISH DATES
July 2017 to Dec 2020
PROJECT DESCRIPTION:.
A systematic review, to assess the evidence of an association between the gastric pathogen, Helicobacter pylori, and Parkinson’s disease (PD), complements a 2018 meta-analysis, upgrading evidence, according to Oxford Centre of Evidence-Based Medicine criteria, to Level 1 for “Does this intervention (Helicobacter eradication) help?”. H. pylori eradication in PD is disease-modifying (even in anti-parkinsonian treatment-naïve patients), but not preventive.
Relative risk of having a non-H. pylori Helicobacter (NHPH), H. suis, in PD patients compared with gastroenterology patients attending for endoscopy was 10 times greater than that of having H. pylori. Hazard-of-death on follow-up was 12 times greater with H. suis-positivity. Zoonosis may explain increased mortality from PD in livestock compared to arable farmers.
What this research has shown.
To corroborate the linked between NHPH, and PD, reliable, non-invasive detection methods are required. (The urea-breath-test is not species-specific, and insensitive to the low infection load of human NHPH infection.) Work was carried out to develop stool-based real-time PCR assays for NHPH screening, involving whole-genome sequencing, comparative genomics. For assessment of analytical sensitivity/specificity, bacterial culture, isolation and archiving of DNA from target/non-target organisms was carried out. Primer and probe design for PCR assays on stool for gastric NHPHs (usual host pig or companion animals) have been completed, along with those for species infecting colon (see below). Optimisation and validation of assays is planned.
Regarding the lower gut and the history of constipation in PD, a colonic transit time study was carried out using oral radio-opaque markers taken over six days, with abdominal x-ray on day seven. Best model for predicting PD-status from bowel dysfunction included segmental delay in transverse colon and functional constipation (Rome criteria). Not only did constipation in PD have distinct localized pathophysiology, but was also associated with bradyphrenia, a slowing of cognitive processing characteristic of PD. Association of bowel dysfunction with depression, irrespective of PD-status, was confirmed. PD has been described as premature ageing: this appeared to include transverse colon function. This is a foundation to exploring links between colonic pathogens/dysbiosis and the specific colonic dysfunction of PD.
Implications
We are now ready for screening livestock (pig) farmers.
PUBLICATIONS & CONFERENCES ATTENDED:
Augustin AD, Savio A, Nevel A, Ellis RJ, Weller C, Taylor D, Tucker RM, Ibrahim MAA, Bjarnason I, Dobbs SM, Dobbs RJ, Charlett A. Helicobacter suis Is Associated With Mortality in Parkinson's Disease. Front Med (Lausanne). 2019 Aug 28;6:188. doi: 10.3389/fmed.2019.00188. PMID: 31555648; PMCID: PMC6724659.
Tucker RM, Ryan S, Hayee BH, Bjarnason I, Augustin AD, Umamahesan C, Taylor D, Weller C, Dobbs SM, Dobbs RJ, Charlett A. Distinctive Pathophysiology Underlying Constipation in Parkinson's Disease: Implications for Cognitive Inefficiency. J Clin Med. 2020 Jun 19;9(6):1916. doi: 10.3390/jcm9061916. PMID: 32575365; PMCID: PMC7356098.
Tucker RM, Augustin AD, Hayee BH, Bjarnason I, Taylor D, Weller C, Charlett A, Dobbs SM, Dobbs RJ. Role of Helicobacters in Neuropsychiatric Disease: A Systematic Review in Idiopathic Parkinsonism. J Clin Med. 2020 Jul 8;9(7):2159. doi: 10.3390/jcm9072159. PMID: 32650535; PMCID: PMC7408992.