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It has been suggested that gut microbiota influence Parkinson's disease (PD) via the gut-brain axis. Here, we examine associations between diet and gut microbiome composition and its predicted functional pathways in patients with PD. We assessed gut microbiota in fecal samples from 85 PD patients in central California using 16S rRNA gene sequencing. Diet quality was assessed by calculating the Healthy Eating Index 2015 (HEI-2015) based on the Diet History Questionnaire II. We examined associations of diet quality, fiber, and added sugar intake with microbial diversity, composition, taxon abundance, and predicted metagenomic profiles, adjusting for age, sex, race/ethnicity, and sequencing platform. Higher HEI scores and fiber intake were associated with an increase in putative anti-inflammatory butyrate-producing bacteria, such as the genera Butyricicoccus and Coprococcus 1. Conversely, higher added sugar intake was associated with an increase in putative pro-inflammatory bacteria, such as the genera Klebsiella. Predictive metagenomics suggested that bacterial genes involved in the biosynthesis of lipopolysaccharide decreased with higher HEI scores, whereas a simultaneous decrease in genes involved in taurine degradation indicates less neuroinflammation. We found that a healthy diet, fiber, and added sugar intake affect the gut microbiome composition and its predicted metagenomic function in PD patients. This suggests that a healthy diet may support gut microbiome that has a positive influence on PD risk and progression.

RESUMEN

BACKGROUND: Prior studies suggested that air pollution exposure may increase the risk of Parkinson's Disease (PD). We investigated the long-term impacts of traffic-related and multiple sources of particulate air pollution on PD in central California. METHODS: Our case-control analysis included 761 PD patients and 910 population controls. We assessed exposure at residential and occupational locations from 1981 to 2016, estimating annual average carbon monoxide (CO) concentrations - a traffic pollution marker - based on the California Line Source Dispersion Model, version 4. Additionally, particulate matter (PM2.5) concentrations were based on a nationwide geospatial chemical transport model. Exposures were assessed as 10-year averages with a 5-year lag time prior to a PD diagnosis for cases and an interview date for controls, subsequently categorized into tertiles. Logistic regression models were used, adjusting for various factors. RESULTS: Traffic-related CO was associated with an increased odds ratio for PD at residences (OR for T3 vs. T1: 1.58; 95% CI: 1.20, 2.10; p-trend = 0.02) and workplaces (OR for T3 vs. T1: 1.91; 95% CI: 1.22, 3.00; p-trend <0.01). PM2.5 was also positively associated with PD at residences (OR for T3 vs. T1: 1.62; 95% CI: 1.22, 2.15; p-trend <0.01) and workplaces (OR for T3 vs. T1: 1.85; 95% CI: 1.21, 2.85; p-trend <0.01). Associations remained robust after additional adjustments for smoking status and pesticide exposure and were consistent across different exposure periods. CONCLUSION: We found that long-term modeled exposure to local traffic-related air pollution (CO) and fine particulates from multiple sources (PM2.5) at homes and workplaces in central California was associated with an increased risk of PD.

Asunto(s)

Contaminantes Atmosféricos , Contaminación del Aire , Enfermedad de Parkinson , Contaminación por Tráfico Vehicular , Humanos , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisis , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/etiología , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Material Particulado/toxicidad , Material Particulado/análisis , Polvo/análisis , California/epidemiología

RESUMEN

INTRODUCTION: Parkinson's disease (PD) is now considered a systemic disease, and some phenotypes may be modifiable by diet. We will compare the diet quality and intake of specific nutrients and food groups of PD patients with household and community controls to examine how diet may influence PD clinical features. METHODS: We conducted a case-control study of 98 PD patients and 83 controls (household = 53; community = 30) in central California, assessing dietary habits over the past month and calculating the Healthy Eating Index (HEI)-2015. We employed multivariate logistic and linear regression analyses to assess associations between diet and PD status, PD symptom profiles, and medication, adjusting for relevant confounders. RESULTS: PD patients had a lower HEI score than controls, with an OR of 0.65 (95% CI: 0.45, 0.94) per 10-points increase in HEI. Lower-quality diet was characterized by higher intakes of carbohydrates, total and added sugars, and trans fats and lower intakes of fiber, folate, unsaturated fatty acids, protein, and fat. PD patients with chronic constipation had a 4.84 point lower HEI score than those without (ß per 10-point in HEI: -0.48; 95% CI: -0.97, -0.00). Furthermore, patients on high dopamine agonist doses consumed more sugar than those on lower doses. CONCLUSION: PD patients consume a lower-quality diet compared to household and community controls. Dietary modifications may alleviate non-motor symptoms like constipation, and promoting a healthy diet should become a part of routine care and disease management for PD patients, with special attention on agonist-treated and hyposmic patients.

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BACKGROUND: DNA methylation studies in Parkinson's disease (PD) thus far have focused on disease susceptibility but not progression. OBJECTIVE: In this epigenome-wide association study (EWAS), we aim to identify methylation markers associated with faster cognitive decline or motor progression in PD. METHODS: We included 232 PD patients from the Parkinson's Environment and Gene follow-up study who provided blood samples at enrolment. Information on cognitive and motor function was collected using the Mini-Mental State Examination (MMSE) and Unified Parkinson's Disease Rating Scale (UPDRS). For EWAS analyses, we used a robust measure of correlation: biweight midcorrelations, t-tests, and Cox proportional hazard models. We also conducted weighted correlation network analysis (WGCNA) to identify CpG modules associated with cognitive decline or motor progression in PD. RESULTS: Among 197 individuals of European ancestry, with our EWAS approach we identified 7 genome-wide significant CpGs associated with a MMSE 4-point decline and 8 CpGs associated with faster motor progression (i.e., rate of UPDRS increase ≥5-point/year). The most interesting CpGs for cognitive decline include cg17445913 in KCNB1 (cor = 0.36, p = 6.85×10-7) and cg02920897 in DLEU2 (cor = 0.34, p = 3.23×10-6), while for motor progression it was cg01754178 in PTPRN2 (cor = - 0.34, p = 2.07×10-6). In WGCNA, motor progression related modules were enriched for genes related to neuronal synaptic functions, Wnt signaling pathway, and mitochondrial apoptosis. CONCLUSIONS: Our study provides the first epigenetic evidence that differential methylation in genes previously identified as being associated with cognitive impairment, neuronal synaptic function, Wnt signaling pathway, and mitochondrial apoptosis is associated with cognitive and motor progression in PD.

Asunto(s)

Disfunción Cognitiva/genética , Metilación de ADN/genética , Epigenoma , Enfermedad de Parkinson/genética , Anciano , Apoptosis/genética , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Masculino , Mitocondrias , Pronóstico , Modelos de Riesgos Proporcionales , ARN Largo no Codificante , Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores/genética , Canales de Potasio Shab/genética , Sinapsis , Transferasas/genética , Vía de Señalización Wnt/genética