Non- Helicobacter pylori Helicobacters, a Treatable Provocateur of Parkinson's Disease: Hypothesis, Evidence and Species Specificity

Abstract

Epidemiological and eradication trial evidence indicates that Helicobacter pylori, a major causative factor in peptic ulcer and gastric cancer, is a driver of the hypokinesia of Parkinson's disease (PD). Psychological (cognitive impairment, depression and anxiety) and gastrointestinal (peptic ulceration and constipation) PD features can precede the symptomatic onset of motor features by decades. We hypothesise that the non-H. pylori Helicobacters (NHPH), which have farm, companion and wild animals as their main hosts, can have a role in PD aetiopathogenesis. In those occupationally at risk of NHPH infection, we address whether there is increased mortality with PD, or depression or suicide. Our systematic review gave evidence that occupational exposure to animals/their products is associated with excess mortality with PD. Indeed, whilst livestock farming increased the risk, crop farming decreased it. Moreover, excess mortality from non-Hodgkin lymphoma in livestock farmers is compatible with NHPH being causal. Our scoping review showed that farmers, veterinarians and abattoir workers have an increased risk of depression and suicide; whether their depression is associated with being down the pathway to PD and/or the presence of Helicobacter infection needs investigation. Regarding Helicobacter species specificity, the link between the presence of NHPH in gastric biopsy and PD was described using a ureA polymerase chain reaction (PCR) assay, targeting the most-commonly named NHPH, H. suis. We describe its redesign and optimisation as a probe-based PCR, confirming the exclusion of H. pylori but not H. suis specificity (additionally identifying 6 species of a 22-NHPH-species panel). The exploration of the zoonotic hypothesis requires a non-invasive pan-Helicobacter PCR screen, allowing the detection and molecular grouping of Helicobacter species.

Keywords: H. pylori; H. suis; Parkinson’s disease; depression; farmers; mortality; non-H. pylori Helicobacters; systematic review.

Figure 1

Limit of detection experiment for the ureA assay, tested against a tenfold dilution series of H. suis DNA. Cycle threshold (Ct) values are tabulated (above). Amplification plots of a 10-fold dilution series on H. suis DNA samples, containing 2.22 × 10⁷ to 2.22 × 10¹ bacterial genome equivalents per reaction, are shown (below). The baseline threshold (horizontal red line) is set at 337800 to optimise signal-to-noise.

Figure 2

Flow chart based on PRISMA guidelines for (a) systematic review of mortality associated with idiopathic Parkinsonism in occupations with exposure to animals and/or their products, and (b) scoping review of depression and suicide in occupations with exposure to animals and/or their products.

Figure 2

Flow chart based on PRISMA guidelines for (a) systematic review of mortality associated with idiopathic Parkinsonism in occupations with exposure to animals and/or their products, and (b) scoping review of depression and suicide in occupations with exposure to animals and/or their products.

Figure 3

Summary of the major findings. From the literature review: (i) the association of Parkinson’s disease (PD) deaths with livestock farming; (ii) the excess non-Hodgkin lymphoma in livestock farmers compatible with non-Helicobacter pylori Helicobacter (NHPH) causality; and (iii) the link between gastric NHPH and PD described using PCR, targeting porcine Helicobacter. From the current investigation: the redesign into a probe-based PCR confirmed H. pylori exclusion but showed a lack of specificity within NHPH. Further exploration of the zoonotic hypothesis requires a pan-Helicobacter screen.