Helicobacter pylori eradication improves motor fluctuations in advanced Parkinson’s disease patients: A prospective cohort study (HP-PD trial)

Abstract

Background Helicobacter pylori (HP) is a bacterium associated with many gastrointestinal (GI) diseases and has shown a high prevalence in Parkinson’s disease (PD). As HP-associated GI dysfunction could affect L-dopa (levodopa) absorption, HP eradication might improve the clinical response and decrease motor fluctuations. Methods A prospective cohort study was conducted on the clinical symptoms of PD patients with motor fluctuations. The 13C-urea breath test was used to diagnose a current HP infection. All patients with HP infection received a 2-week regimen of triple therapy. The changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score, L-dopa onset time, wearing-off symptoms, mean daily on-off time, GI symptom scores, and quality of life score were measured at baseline and at a 6-week follow-up. Results A total of 163 PD patients were assessed, of whom 40 were enrolled. Fifty-five percent of the enrolled patients (22/40) had a current HP infection, whereas HP eradication was identified in 17 of 22 (77.3%) patients who received eradication therapy. Patients with HP eradication showed a significant decrease in daily ‘off’ time (4.0 vs. 4.7 h, p = 0.040) and an increase in daily ‘on’ time (11.8 vs. 10.9 h, p = 0.009). Total wearing-off score (4.4 vs. 6.0, p = 0.001) and the GI symptom score (8.1 vs. 12.8, p = 0.007) were significantly improved. There was no significant improvement in L-dopa onset time, UPDRS motor score, or quality of life score. Conclusions HP eradication leads to significant clinical improvement in the symptoms of PD. Eradication of HP not only increases the total daily ‘on’ time but also decreases wearing-off symptoms and improves GI symptoms.

Gut–Brain Axis as a Pathological and Therapeutic Target for Neurodegenerative Disorders

“…In parallel, the eradication of H. pylori in PD animals improved the absorption of the levodopa and reduced the motor symptoms [96,97]. In PD patients, worsening of motor severity proceeds with an infection of H. pylori [97]. Taken together, these findings suggest the close interaction of GBA in PD pathology and treatment.…”

“…The incorrect folding of α-synuclein is rampant in the intestinal microbiota of PD animals and accompanies the peripheral damage in dopaminergic neurons [95]. In parallel, the eradication of H. pylori in PD animals improved the absorption of the levodopa and reduced the motor symptoms [96,97]. In PD patients, worsening of motor severity proceeds with an infection of H. pylori [97].…”

Microbial Infections Are a Risk Factor for Neurodegenerative Diseases

“…Several studies have shown that eradicating H. pylori infection improved motor function of PD patients by increasing oral drug absorption ( Pierantozzi et al, 2006 ; Lahner et al, 2009 ). A recent cohort study showed that PD patients with successful H. pylori eradication therapy exhibited improved clinical PD symptoms, including tremors, mood, and gastrointestinal distress, compared with patients with failed H. pylori eradication therapy ( Lolekha et al, 2021 ). Patients with active H. pylori infection had longer mean levodopa onset time, suggesting that H. pylori may interfere with the bioavailability of levodopa, possibly because of increased gastric inflammation, delayed gastric emptying, and/or impaired active transport of levodopa to the site of absorption ( Lolekha et al, 2021 ).…”

“…A recent cohort study showed that PD patients with successful H. pylori eradication therapy exhibited improved clinical PD symptoms, including tremors, mood, and gastrointestinal distress, compared with patients with failed H. pylori eradication therapy ( Lolekha et al, 2021 ). Patients with active H. pylori infection had longer mean levodopa onset time, suggesting that H. pylori may interfere with the bioavailability of levodopa, possibly because of increased gastric inflammation, delayed gastric emptying, and/or impaired active transport of levodopa to the site of absorption ( Lolekha et al, 2021 ). Though much is still unclear of the involvement of H. pylori in the etiopathogenesis of PD, these data indicate that it is prevalent in PD patients and may exacerbate the symptoms of PD by interfering with levodopa bioavailability.…”

Gastric Helicobacter suis Infection Partially Protects against Neurotoxicity in A 6-OHDA Parkinson’s Disease Mouse Model

“…In addition, 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 ], although a recent randomized control study could not confirm this hypothesis [ 27 ].…”