Abstract
The exact etiology of Parkinson’s disease (PD) remains largely unknown, but more and more research suggests the involvement of the gut microbiota. Interestingly, idiopathic PD patients were shown to have at least a 10 times higher prevalence of Helicobacter suis (H. suis) DNA in gastric biopsies compared to control patients. H. suis is a zoonotic Helicobacter species that naturally colonizes the stomach of pigs and non-human primates but can be transmitted to humans. Here, we investigated the influence of a gastric H. suis infection on PD disease progression through a 6-hydroxydopamine (6-OHDA) mouse model. Therefore, mice with either a short- or long-term H. suis infection were stereotactically injected with 6-OHDA in the left striatum and sampled one week later. Remarkably, a reduced loss of dopaminergic neurons was seen in the H. suis/6-OHDA groups compared to the control/6-OHDA groups. Correspondingly, motor function of the H. suis-infected 6-OHDA mice was superior to that in the non-infected 6-OHDA mice. Interestingly, we also observed higher expression levels of antioxidant genes in brain tissue from H. suis-infected 6-OHDA mice, as a potential explanation for the reduced 6-OHDA-induced cell loss. Our data support an unexpected neuroprotective effect of gastric H. suis on PD pathology, mediated through changes in oxidative stress.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, affecting more than 6 million people worldwide in 2016 and exceeding 12–17 million by 2040 [1,2]
H. pylori infection may affect the bioavailability of levodopa, which is used for PD treatment, resulting in worse motor control in H. pylori-infected PD patients [22]
For the long-term infected mice, we observed a significant increase in gene expression for Gclc, Gclm, glutathione-disulfide reductase (Gsr), heme oxygenase 1 (Hmox1), and Nox2 in parallel to the changes seen in nuclear factor (erythroid-derived 2)-like 2 (Nrf2) when comparing the H. suis/6-OHDA mice with the control/6-OHDA mice (Figure 8D,F,H,J,L)
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, affecting more than 6 million people worldwide in 2016 and exceeding 12–17 million by 2040 [1,2]. A gastric Helicobacter (H.) pylori infection has already been associated to an increased risk of developing PD, and with worse motor function in established PD [15,16,17,18,19,20,21]. H. pylori infection may affect the bioavailability of levodopa, which is used for PD treatment, resulting in worse motor control in H. pylori-infected PD patients [22]. H. pylori eradication has been suggested to result in improvement of PD-related motor symptoms [16,17,19,23,24,25,26], a recent randomized control study could not confirm this hypothesis [27]
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