Original Research ARTICLE
Helicobacter suis is associated with Mortality in Parkinson’s disease
- 1King's College Hospital NHS Foundation Trust, United Kingdom
- 2Royal Marsden Hospital, United Kingdom
- 3Royal Veterinary College (RVC), United Kingdom
- 4Animal and Plant Health Agency (United Kingdom), United Kingdom
- 5King's College London, United Kingdom
Helicobacter pylori has been implicated in the pathogenesis of Parkinson’s disease (PD). Its eradication, in a randomised placebo-controlled trial, improved PD hypokinesia. Helicobacter species zoonosis might explain excess mortality from PD and non-Hodgkin lymphoma in livestock, but not arable, farmers. Indeed, Helicobacter is causally-associated with gastric lymphoma. We have previously shown that the relative-frequency, H. suis to H. pylori, was 10-times greater in 60 PD-patients than in 256 controls. We now go on to evaluate the pathological significance of H. suis, detected in gastric-biopsy DNA-extracts by ureA-based species-specific qPCR, validated by amplicon sequencing. The methodology had been cross-validated by a carR-based PCR. The pathological significance is put in context of H. pylori detection [urea-breath-test (UBT) with biopsy-culture, and, if negative, PCR], and potential reservoir in pigs. Here, we explore, in these 60 PD-patients, associations of H. suis status with all-cause-mortality, and with orthostatic cardiovascular and blood profiling. H. suis had been detected in 19 of the 60 PD-patients on one or more occasion, only two (with co-existent H. pylori) being urea breath test (UBT) positive. We found that the hazard-of-death (age-at-diagnosis- and gender-adjusted) was 12 (95% CI 1, 103) times greater (likelihood-ratio test, P=0.005) with H. suis-positivity (6/19) than with negativity (2/40: one lost to follow-up). UBT-values did not influence the hazard. H. suis-positivity was associated with lower standing mean-arterial-pressure (6 (1, 11) mmHg), H. pylori-positivity having no effect. The lower total lymphocyte count with H. pylori-positivity (-8 (-1, -14) %) was not seen with H. suis, where T-cell counts were higher (24 (2, 52) %). Regarding the potential zoonotic reservoir in the UK, Helicobacter-like-organism frequency was determined in freshly-slaughtered pigs, nature ascertained by sequencing. Organisms immunostaining for Helicobacter, with corkscrew morphology typical of non-H. pylori Helicobacter, were seen in 47% of 111 pig-antra. We conclude that H. suis is associated with all-cause-mortality in PD and has a potential zoonotic reservoir.
Keywords: Mortality, Parkinson's disease, Helicobacter suis, Helicobacter pylori, pig
Received: 19 Dec 2018;
Accepted: 05 Aug 2019.
Copyright: © 2019 Augustin, Savio, Nevel, Ellis, Weller, Taylor, Tucker, Ibrahim, Bjarnason, Dobbs, Dobbs and Charlett. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Sylvia Dobbs, King's College London, London, United Kingdom, firstname.lastname@example.org