Abstract
Helicobacter pylori has been implicated in the pathogenesis of Parkinson's disease (PD). Its eradication, in a randomized 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 the 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 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.
Highlights
In the one randomized, double-blind, placebo-controlled trial (RCT) of the effect of biopsy-proven Helicobacter pylori eradication on the facets of Parkinson’s disease (PD), we found sustained, clinically relevant improvement in objectivelymeasured hypokinesia [1, 2], providing 1b level causative evidence [3]
We found the relative-frequency of H. suis to H. pylori, to be 10-times greater in PD, when comparing gastric biopsies from 60 PD-patients with those from 256 routine gastroenterology patients [9] (H. suis frequency was standardized against that of H. pylori to avoid it being construed as true prevalence.) Results of the species-specific ureAB genecluster based RT-PCR employed were confirmed by sequencing the amplicon
It could represent expansion of previously hidden infection into a niche left by H. pylori eradication [9]
Summary
Double-blind, placebo-controlled trial (RCT) of the effect of biopsy-proven Helicobacter pylori eradication on the facets of Parkinson’s disease (PD), we found sustained, clinically relevant improvement in objectivelymeasured hypokinesia [1, 2], providing 1b level causative evidence [3]. A single case of eradicating a corkscrew-shaped nonHelicobacter pylori Helicobacter (NHPH) has been described in a breath-test-positive PD-patient with antral gastritis [7]. Biopsy-proven eradication in this cachectic patient, who had been wheelchair-bound for over a year, resulted in a Uturn in brady/hypokinesia, mastering previously neglected computing skills, and normalization of body mass index. Clinical relapse with return of breath-test positivity had occurred 14 weeks after giving a first-line anti-H. pylori regimen, but the lasting improvement followed exhibition of quadruple therapy containing oxytetracycline and bismuth. Repeat biopsy in the PD-patient, 11 months after the quadruple therapy showed almost complete resolution of gastritis, with no organisms [7]
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