RESUMEN

Background: Increasing evidence suggests an association between Helicobacter pylori (HP) infection and Parkinson's disease (PD) and its clinical manifestations, but the causal relationship remain largely unknown. Objective: To investigate the causal relationship between HP infection and PD risk, PD symptoms, and secondary parkinsonism, we conducted two-sample Mendelian randomization (MR). Methods: We obtained summary data from genome-wide association studies for seven different antibodies specific to HP proteins and five PD-related phenotypes. The inverse-variance weighted (IVW), weighted median, weighted mode, and MR-Egger methods were used to assess the causal relationships. Sensitivity analyses were performed to examine the stability of the MR results and reverse MR analysis was conducted to evaluate the presence of reverse causality. Results: Genetically predicted HP antibodies were not causally associated with an increased risk of PD. However, HP cytotoxin-associated gene-A (CagA) and outer membrane protein (OMP) antibody level were causally associated with PD motor subtype (tremor to postural instability/gait difficulty score ratio; ß = -0.16 and 0.46, P = 0.002 and 0.048, respectively). HP vacuolating cytotoxin-A (VacA) antibody level was causally associated with an increased risk of PD dementia [odds ratio (OR) = 1.93, P = 0.040]. Additionally, HP OMP antibody level was identified as a risk factor for drug-induced secondary parkinsonism (OR = 2.08, P = 0.033). These results were stable, showed no evidence of heterogeneity or directional pleiotropy, and no evidence of a reverse causal relationship. Conclusions: Our findings indicate that HP infection does not increase the risk of PD, but contributes to PD motor and cognitive symptoms. Different types of HP antibodies affect different symptoms of PD. Eradication of HP infection may help modulate and improve symptoms in PD patients.

Asunto(s)

Anticuerpos Antibacterianos , Estudio de Asociación del Genoma Completo , Infecciones por Helicobacter , Helicobacter pylori , Análisis de la Aleatorización Mendeliana , Enfermedad de Parkinson , Humanos , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/inmunología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/inmunología , Enfermedad de Parkinson/etiología , Helicobacter pylori/inmunología , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Factores de Riesgo

RESUMEN

The role of microbiological factors in the development of neurodegenerative diseases is attracting increasing attention, while the relationship remains debated. This study aimed to comprehensively summarize and evaluate the associations between microbiological factors and the risk of neurodegenerative disorders with an umbrella review. PubMed, Embase, and the Cochrane library were used to search for papers from the earliest to March 2021 for identifying meta-analyses and systematic reviews that examined associations between microbiological factors and neurodegenerative diseases. AMSTAR2 tool was employed to evaluate the methodical quality of systematic reviews and meta-analyses. The effect size and 95% confidence interval (95% CI) were recalculated with a random effect model after the overlap was recognized by the corrected covered area (CCA) method. The heterogeneity of each meta-analysis was measured by the I 2 statistic and 95% prediction interval (95% PI). Additionally, publication bias and the quality of evidence were evaluated for all 37 unique associations. Only 4 associations had above the medium level of evidence, and the rest associations presented a low level of evidence. Among them, helicobacter pylori (HP), infection, and bacteria are associated with Parkinson's disease (PD), and the other one verifies that periodontal disease is a risk factor for all types of dementia. Following the evidence of our study, eradication of HP and aggressive treatment of periodontitis are beneficial for the prevention of PD and dementia, respectively. This umbrella review provides comprehensive quality-grade evidence on the relationship between microbial factors and neurodegenerative disease. Regardless of much evidence linking microbial factors to neurodegenerative diseases, these associations are not necessarily causal, and the evidence level is generally low. Thus, more effective studies are required. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, PROSPERO, identifier: CRD42021239512.