The Role of the Western Diet and Oral Microbiota in Parkinson’s Disease

The type of diet not only affects the composition of the oral microflora but is also one of the more critical factors associated with an increased risk of Parkinson’s disease, PD. This study compared diet preferences and oral microbiota profiles in patients with PD vs. healthy controls. This study compared the oral microbiota composition of 59 patients with PD and 108 healthy controls (without neurodegeneration) using 16S rRNA gene amplicon sequencing. According to results, oral microbiota in patients with PD is different compared from healthy controls. In particular, decreased abundance of Proteobacteria, Pastescibacteria, and Tenercutes was observed. The oral cavity of patients with PD was characterized by the high relative abundance of bacteria from the genera Prevotella, Streptococcus, and Lactobaccillus. There were also differences in food preferences between patients with PD and healthy controls, which revealed significantly higher intake of margarine, fish, red meat, cereals products, avocado, and olives in the patients with PD relative to healthy controls. Strong positive and negative correlations between specific food products and microbial taxa were identified.

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Deep nasal sinus cavity microbiota dysbiosis in Parkinson’s disease

npj Parkinson s Disease ◽

10.1038/s41531-021-00254-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Gian Pal ◽

Vivian Ramirez ◽

Phillip A. Engen ◽

Ankur Naqib ◽

Christopher B. Forsyth ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Olfactory Bulb ◽

Nasal Cavity ◽

Amplicon Sequencing ◽

Motor Symptom ◽

Rrna Gene ◽

Healthy Controls ◽

Nasal Sinus ◽

Severe Motor

AbstractOlfactory dysfunction is a pre-motor symptom of Parkinson’s disease (PD) that appears years prior to diagnosis and can affect quality of life in PD. Changes in microbiota community in deep nasal cavity near the olfactory bulb may trigger the olfactory bulb-mediated neuroinflammatory cascade and eventual dopamine loss in PD. To determine if the deep nasal cavity microbiota of PD is significantly altered in comparison to healthy controls, we characterized the microbiota of the deep nasal cavity using 16S rRNA gene amplicon sequencing in PD subjects and compared it to that of spousal and non-spousal healthy controls. Correlations between microbial taxa and PD symptom severity were also explored. Olfactory microbial communities of PD individuals were more similar to those of their spousal controls than to non-household controls. In direct comparison of PD and spousal controls and of PD and non-spousal controls, significantly differently abundant taxa were identified, and this included increased relative abundance of putative opportunistic-pathobiont species such as Moraxella catarrhalis. M. catarrhalis was also significantly correlated with more severe motor scores in PD subjects. This proof-of-concept study provides evidence that potential pathobionts are detected in the olfactory bulb and that a subset of changes in the PD microbiota community could be a consequence of unique environmental factors associated with PD living. We hypothesize that an altered deep nasal microbiota, characterized by a putative pro-inflammatory microbial community, could trigger neuroinflammation in PD.

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Oral Dysbiosis and Inflammation in Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202459 ◽

2021 ◽

Vol 11 (2) ◽

pp. 619-631

Author(s):

Vanessa Fleury ◽

Alkisti Zekeridou ◽

Vladimir Lazarevic ◽

Nadia Gaïa ◽

Catherine Giannopoulou ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dental Plaque ◽

Gingival Crevicular Fluid ◽

Amplicon Sequencing ◽

Interferon Γ ◽

Oral Microbiome ◽

Rrna Gene ◽

Oral Microbiota ◽

Tnf Α

Background: Oral microbiota has largely escaped attention in Parkinson’s disease (PD), despite its pivotal role in maintaining oral and systemic health. Objective: The aim of our study was to examine the composition of the oral microbiota and the degree of oral inflammation in PD. Methods: Twenty PD patients were compared to 20 healthy controls. Neurological, periodontal and dental examinations were performed as well as dental scaling and gingival crevicular fluid sampling for cytokines measurement (interleukine (IL)-1β, IL-6, IL-1 receptor antagonist (RA), interferon-γ and tumor necrosis factor (TNF)-α). Two months later, oral microbiota was sampled from saliva and subgingival dental plaque. A 16S rRNA gene amplicon sequencing was used to assess bacterial communities. Results: PD patients were in the early and mid-stage phases of their disease (Hoehn & Yahr 2–2.5). Dental and periodontal parameters did not differ between groups. The levels of IL-1β and IL-1RA were significantly increased in patients compared to controls with a trend for an increased level of TNF-α in patients. Both saliva and subgingival dental plaque microbiota differed between patients and controls. Streptococcus mutans, Kingella oralis, Actinomyces AFQC_s, Veillonella AFUJ_s, Scardovia, Lactobacillaceae, Negativicutes and Firmicutes were more abundant in patients, whereas Treponema KE332528_s, Lachnospiraceae AM420052_s, and phylum SR1 were less abundant. Conclusion: Our findings show that the oral microbiome is altered in early and mid-stage PD. Although PD patients had good dental and periodontal status, local inflammation was already present in the oral cavity. The relationship between oral dysbiosis, inflammation and the pathogenesis of PD requires further study.

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Oral Factors That Impact the Oral Microbiota in Parkinson’s Disease

Microorganisms ◽

10.3390/microorganisms9081616 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1616

Author(s):

Natalia S. Rozas ◽

Gena D. Tribble ◽

Cameron B. Jeter

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Oral Health ◽

Soft Tissue ◽

Oral Hygiene ◽

Beta Diversity ◽

Oral Microbiota ◽

Healthy Controls ◽

Microbiota Composition ◽

Salivary Ph

Patients with Parkinson’s disease (PD) are at increased risk of aspiration pneumonia, their primary cause of death. Their oral microbiota differs from healthy controls, exacerbating this risk. Our goal was to explore if poor oral health, poor oral hygiene, and dysphagia status affect the oral microbiota composition of these patients. In this cross-sectional case-control study, the oral microbiota from hard and soft tissues of patients with PD (n = 30) and age-, gender-, and education-matched healthy controls (n = 30) was compared using 16S rRNA gene sequencing for bacterial identification. Study participants completed dietary, oral hygiene, drooling, and dysphagia questionnaires, and an oral health screening. Significant differences in soft tissue beta-diversity (p < 0.005) were found, and a higher abundance of opportunistic oral pathogens was detected in patients with PD. Factors that significantly influenced soft tissue beta-diversity and microbiota composition include dysphagia, drooling (both p < 0.05), and salivary pH (p < 0.005). Thus, patients with PD show significant differences in their oral microbiota compared to the controls, which may be due, in part, to dysphagia, drooling, and salivary pH. Understanding factors that alter their oral microbiota could lead to the development of diagnostic and treatment strategies that improve the quality of life and survivability of these patients.

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The role of one-carbon metabolism and homocysteine in Parkinson’s disease onset, pathology and mechanisms

Nutrition Research Reviews ◽

10.1017/s0954422419000106 ◽

2019 ◽

Vol 32 (2) ◽

pp. 218-230 ◽

Cited By ~ 4

Author(s):

Lauren K. Murray ◽

Nafisa M. Jadavji

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Carbon Metabolism ◽

Animal Studies ◽

B Vitamins ◽

Present Review ◽

Increased Risk ◽

One Carbon Metabolism ◽

B Vitamin

AbstractParkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterised by the progressive degeneration of dopaminergic (DA) neurons. The cause of degeneration is not well understood; however, both genetics and environmental factors, such as nutrition, have been implicated in the disease process. Deficiencies in one-carbon metabolism in particular have been associated with increased risk for PD onset and progression, though the precise relationship is unclear. The aim of the present review is to determine the role of one-carbon metabolism and elevated levels of homocysteine in PD onset and pathology and to identify potential mechanisms involved. A search of PubMed, Google Scholar and Web of Science was undertaken to identify relevant human and animal studies. Case–control, prospective cohort studies, meta-analyses and non-randomised trials were included in the present review. The results from human studies indicate that polymorphisms in one-carbon metabolism may increase risk for PD development. There is an unclear role for dietary B-vitamin intake on PD onset and progression. However, dietary supplementation with B-vitamins may be beneficial for PD-affected individuals, particularly those on l-DOPA (levodopa or l-3,4-dihydroxyphenylalanine) treatment. Additionally, one-carbon metabolism generates methyl groups, and methylation capacity in PD-affected individuals is reduced. This reduced capacity has an impact on expression of disease-specific genes that may be involved in PD progression. During B-vitamin deficiency, animal studies report increased vulnerability of DA cells through increased oxidative stress and altered methylation. Nutrition, especially folates and related B-vitamins, may contribute to the onset and progression of PD by making the brain more vulnerable to damage; however, further investigation is required.

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Genetic Variants in SNCA and the Risk of Sporadic Parkinson’s Disease and Clinical Outcomes: A Review

Parkinson s Disease ◽

10.1155/2017/4318416 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Clarissa Loureiro das Chagas Campêlo ◽

Regina Helena Silva

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Environmental Factors ◽

Clinical Outcomes ◽

Association Studies ◽

Clinical Aspects ◽

Genome Wide Association Studies ◽

Snca Gene ◽

Increased Risk

There is increasing evidence of the contribution of genetic susceptibility to the etiology of Parkinson’s disease (PD). Genetic variations in the SNCA gene are well established by linkage and genome-wide association studies. Positive associations of single nucleotide polymorphisms (SNPs) in SNCA and increased risk for PD were found. However, the role of SNCA variants in individual traits or phenotypes of PD is unknown. Here, we reviewed the current literature and identified 57 studies, performed in fourteen different countries, that investigated SNCA variants and susceptibility to PD. We discussed the findings based on environmental factors, history of PD, clinical outcomes, and ethnicity. In conclusion, SNPs within the SNCA gene can modify the susceptibility to PD, leading to increased or decreased risk. The risk associations of some SNPs varied among samples. Of notice, no studies in South American or African populations were found. There is little information about the effects of these variants on particular clinical aspects of PD, such as motor and nonmotor symptoms. Similarly, evidence of possible interactions between SNCA SNPs and environmental factors or disease progression is scarce. There is a need to expand the clinical applicability of these data as well as to investigate the role of SNCA SNPs in populations with different ethnic backgrounds.

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Parkinson’s disease-associated alterations of the gut microbiome can invoke disease-relevant metabolic changes

10.1101/691030 ◽

2019 ◽

Author(s):

Federico Baldini ◽

Johannes Hertel ◽

Estelle Sandt ◽

Cyrille C. Thinnes ◽

Lorieza Neuberger-Castillo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gut Microbiome ◽

Systemic Disease ◽

Rrna Gene ◽

Healthy Controls ◽

Microbial Metabolites ◽

Metabolic Modelling ◽

Microbiome Composition ◽

Relative Abundances

ABSTRACTParkinson’s disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we first analysed the gut microbiome of patients and healthy controls by 16S rRNA gene sequencing of stool samples from the Luxembourg Parkinson’s study (n=147 typical PD cases, n=162 controls). All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include: 1. eight genera and nine species changed significantly in their relative abundances between PD patients and healthy controls. 2. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. The relative abundances ofBilophilaandParaprevotellawere significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. In contrast, dopaminergic medication had no detectable effect on the PD microbiome composition. 3. Personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms and attributed to individual bacteria, such asAkkermansia muciniphilaandBilophila wardswarthia. Our results suggest that PD-associated alterations of gut microbiome could translate into functional differences affecting host metabolism and disease phenotype.

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Comprehensive assessment of PINK1 variants in Parkinson’s disease

10.1101/2020.01.21.20018101 ◽

2020 ◽

Cited By ~ 1

Author(s):

Lynne Krohn ◽

Francis P. Grenn ◽

Mary B. Makarious ◽

Jonggeol Jeffrey Kim ◽

Sara Bandres-Ciga ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Risk Factor ◽

Autosomal Recessive ◽

Disease Susceptibility ◽

Large Datasets ◽

The Past ◽

Increased Risk ◽

Early Onset Parkinson’S Disease

AbstractMultiple genes have been associated with monogenic Parkinson’s disease and Parkinsonism syndromes. Mutations in PINK1 (PARK6) have been shown to result in autosomal recessive early onset Parkinson’s disease. In the past decade, several studies have suggested that carrying a single heterozygous PINK1 mutation is associated with increased risk for Parkinson’s disease. Here we comprehensively assess the role of PINK1 variants in Parkinson’s disease susceptibility using several large datasets totalling 376,558 individuals including: 13,708 Parkinson’s disease cases and 362,850 controls. After combining these data, we did not find evidence to support a role for heterozygous PINK1 mutations as a risk factor for Parkinson’s disease.

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Diabetes and Parkinson’s Disease: Debating the Link Through Ca2+/cAMP Signalling

Current Diabetes Reviews ◽

10.2174/1573399815666190711113644 ◽

2020 ◽

Vol 16 (3) ◽

pp. 238-241 ◽

Cited By ~ 3

Author(s):

Leandro B. Bergantin

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neuronal Death ◽

Potential Role ◽

Insulin Signalling ◽

Signalling Pathways ◽

Camp Signalling ◽

Increased Risk

Background: A link between diabetes and Parkinson´s disease (PD) has been established by several reports. Consistent data report that people diagnosed with diabetes have demonstrated an enhanced risk of manifesting PD in their lifetime. The working principles involved in this link have been extensively discussed. Over the last decade, diabetes has been reported to be correlated with an increased risk of dementia, suggesting a potential role of diabetes, or insulin signalling dysregulations, in neurodegeneration. In addition, it is nowadays highly debated that dysregulations related to Ca2+ signalling may be an upstream issue which could also link diabetes and PD. Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling) control both the neurotransmitters/hormones release and neuronal death. Conclusion: Considering our previous reports about Ca2+/cAMP signalling, the putative contribution of Ca2+/cAMP signalling in this link (between diabetes and PD) is discussed in this paper.

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Association study of DNAJC13, UCHL1, HTRA2, GIGYF2 and EIF4G1 with Parkinson’s disease

10.1101/2020.06.26.20141176 ◽

2020 ◽

Author(s):

Prabhjyot Saini ◽

Uladzislau Rudakou ◽

Eric Yu ◽

Jennifer A. Ruskey ◽

Farnaz Asayesh ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Association Study ◽

Rare Variants ◽

Multiple Comparisons ◽

Association Tests ◽

Rare Mutations ◽

Increased Risk ◽

Molecular Inversion Probes

AbstractRare mutations in genes originally discovered in multi-generational families have been associated with increased risk of Parkinson’s Disease (PD). The involvement of rare variants in DNAJC13, UCHL1, HTRA2, GIGYF2 and EIF4G1 loci have been poorly studied or produced conflicting results across cohorts. However, they are still being often referred to as “PD-genes” and used in different models. To further elucidate the role of these five genes in PD, we fully sequenced them using molecular inversion probes in 2,408 PD patients and 3,444 controls from 3 different cohorts. A total of 788 rare variants were identified across the five genes and three cohorts. Burden analyses and optimized sequence Kernel association tests revealed no significant association between any of the genes and PD after correction for multiple comparisons. Our results do not support an association of the five tested genes with PD. Combined with previous studies, it is unlikely that any of these genes plays an important role in PD. Their designation as “PARK” genes should be reconsidered.

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Genetic Markers as Risk Factors for the Development of Impulsive-Compulsive Behaviors in Patients with Parkinson’s Disease Receiving Dopaminergic Therapy

Journal of Personalized Medicine ◽

10.3390/jpm11121321 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1321

Author(s):

Anna Fedosova ◽

Nataliya Titova ◽

Zarema Kokaeva ◽

Natalia Shipilova ◽

Elena Katunina ◽

...

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Control Group ◽

Drug Induced ◽

Increased Risk ◽

Compulsive Behaviors ◽

Healthy Control ◽

Pcr Techniques

Impulsive–compulsive and related behavioral disorders (ICD) are drug-induced non-motor symptoms of Parkinson’s disease (PD). Recently research has focused on evaluating whether ICD could be predicted and managed using a pharmacogenetic approach based on dopaminergic therapies, which are the main risk factors. The aim of our study was to evaluate the role of candidate genes such as DBH, DRD2, MAOA, BDNF, COMT, SLC6A4, SLC6A3, ACE, DRD1 gene polymorphisms in the pathogenesis of ICD in PD. We compared patients with PD and ICD (n = 49), patients with PD without ICD (n = 36) and a healthy control group (n = 365). ICD was diagnosed using the QUIP questionnaires and specific diagnostic criteria for subtypes of ICD. Genotyping was conducted using a number of PCR techniques and SNaPshot. Statistical analysis was performed using WinPepi and APSampler v3.6 software. PCA testing was conducted using RStudio software v1.4.1106-5. The following substitutions showed statistically significant correlations with PD and ICD: DBH (rs2097629, rs1611115), DRD2 (rs6275, rs12364283, rs1076560), ACE (rs4646994), DRD1 (rs686), BDNF (rs6265), these associations are novel in Russian PD patients. Our findings suggest that polymorphisms in DBH, BDNF, DRD2, ACE genes in Russian subjects are associated with an increased risk of ICD development.

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