Helicobacter pylori Eradication in Parkinson's Disease: A Randomized Placebo-Controlled Trial.

BACKGROUND: Helicobacter pylori (HP) infection has been associated with worse motor function in Parkinson's disease (PD). OBJECTIVE: We aimed to evaluate the effects of HP eradication on PD symptoms. METHODS: In this parallel-group, double-blind, randomized placebo-controlled, single-center trial, patients with PD with positive HP urea breath test and serology were block randomized (1:1) to receive standard eradication triple therapy or identically appearing placebo capsules for 1 week. Prespecified motor (International Parkinson and Movement Disorder Society Unified PD Rating Scale [MDS-UPDRS], timed tests, and home-based wearable sensor measurements), nonmotor (Leeds Dyspepsia Questionnaire and Montreal Cognitive Assessment), and quality-of-life (Parkinson's Disease Questionnaire-39) outcome measures were assessed at weeks 6, 12, 24, and 52. The primary outcome was the baseline-to-week 12 change in ON medication MDS-UPDRS motor scores. Lactulose-hydrogen breath testing for concomitant small intestinal bacterial overgrowth was performed at baseline and repeated at week 24, together with the urea breath test. RESULTS: A total of 310 patients were screened for eligibility and 80 were randomly assigned, of whom 67 were included in the full-analysis set (32 treatment group patients, 35 placebo patients). HP eradication did not improve MDS-UPDRS motor scores at week 12 (mean difference 2.6 points in favor of placebo, 95% confidence interval: -0.4 to 5.6, P = 0.089). There was no significant improvement in any motor, nonmotor, or quality-of-life outcome at weeks 12 and 52. Both the full-analysis and per-protocol analyses (based on eradication status) supported these conclusions. Small intestinal bacterial overgrowth status did not influence treatment results. CONCLUSIONS: HP eradication does not improve clinical outcomes in PD, suggesting that there is no justification for routine HP screening or eradication with the goal of improving PD symptoms. © 2020 International Parkinson and Movement Disorder Society.

Redundant Innate and Adaptive Sources of IL17 Production Drive Colon Tumorigenesis.

IL17-producing Th17 cells, generated through a STAT3-dependent mechanism, have been shown to promote carcinogenesis in many systems, including microbe-driven colon cancer. Additional sources of IL17, such as γδ T cells, become available under inflammatory conditions, but their contributions to cancer development are unclear. In this study, we modeled Th17-driven colon tumorigenesis by colonizing Min(Ap) (c+/-) mice with the human gut bacterium, enterotoxigenic Bacteroides fragilis (ETBF), to investigate the link between inflammation and colorectal cancer. We found that ablating Th17 cells by knocking out Stat3 in CD4(+) T cells delayed tumorigenesis, but failed to suppress the eventual formation of colonic tumors. However, IL17 blockade significantly attenuated tumor formation, indicating a critical requirement for IL17 in tumorigenesis, but from a source other than Th17 cells. Notably, genetic ablation of γδ T cells in ETBF-colonized Th17-deficient Min mice prevented the late emergence of colonic tumors. Taken together, these findings support a redundant role for adaptive Th17 cell- and innate γδT17 cell-derived IL17 in bacteria-induced colon carcinogenesis, stressing the importance of therapeutically targeting the cytokine itself rather than its cellular sources. Cancer Res; 76(8); 2115-24. ©2016 AACR.

Helicobacter pylori infection is associated with worse severity of Parkinson's disease.

BACKGROUND: Some studies have suggested that chronic Helicobacter pylori (HP) infection can aggravate the neurodegenerative process in Parkinson's disease (PD), and targeted intervention could potentially modify the course of this disabling disease. We aimed to study the impact of HP infection on motor function, gastrointestinal symptoms, and quality of life in a large cohort of PD patients. METHODS: 102 consecutive PD patients underwent (13)C urea breath testing and blinded evaluations consisting of the Unified Parkinson's Disease Rating Scale (UPDRS) including "On"-medication motor examination (Part III), objective and quantitative measures of bradykinesia (Purdue Pegboard and timed gait), Leeds Dyspepsia Questionnaire, and PDQ-39 (a health-related quality of life questionnaire). RESULTS: 32.4% of PD patients were HP-positive. HP-positive patients were older (68.4 ± 7.3 vs. 63.8 ± 8.6 years, P = 0.009) and had worse motor function (UPDRS Part III 34.0 ± 13.0 vs. 27.3 ± 10.0, P = 0.04; Pegboard 6.4 ± 3.3 vs. 8.0 ± 2.7 pins, P = 0.04; and timed gait 25.1 ± 25.4 vs. 15.5 ± 7.6 s, P = 0.08). In the multivariate analysis, HP status demonstrated significant main effects on UPDRS Part III and timed gait. The association between HP status and these motor outcomes varied according to age. Gastrointestinal symptoms and PDQ-39 Summary Index scores did not differ between the two groups. CONCLUSIONS: This is the largest cross-sectional study to demonstrate an association between HP positivity and worse PD motor severity.