Altered gut microbiota in Parkinson's disease patients with motor complications

Telomeres, which are repetitive sequences that cap the end of the chromosomes, shorten with each cell division. Besides cellular aging, there are several other factors that influence telomere length (TL), in particular, oxidative stress and inflammation, which play an important role in the pathogenesis of neurodegenerative brain diseases including Parkinson’s disease (PD). So far, the majority of studies have not demonstrated a significant difference in TL between PD patients and healthy individuals. However, studies investigating the effect of TL on the symptomatology and disease progression of PD are scarce, and thus, warranted. We analyzed TL of peripheral blood cells in a sample of 204 PD patients without concomitant autoimmune diseases and analyzed its association with several PD related phenotypes. Monochrome multiplex quantitative PCR (mmqPCR) was used to determine relative TL given as a ratio of the amount of DNA between the telomere and albumin as the housekeeping gene. We found a significant difference in the relative TL between PD patients with and without dementia, where shorter TL presented higher risk for dementia (p = 0.024). However, the correlation was not significant after adjustment for clinical factors (p = 0.509). We found no correlations between TLs and the dose of dopaminergic therapy when the analysis was adjusted for genetic variability in inflammatory or oxidative factors. In addition, TL influenced time to onset of motor complications after levodopa treatment initiation (p = 0.0134), but the association did not remain significant after adjustment for age at inclusion and disease duration (p = 0.0781). Based on the results of our study we conclude that TL contributes to certain PD-related phenotypes, although it may not have a major role in directing the course of the disease. Nevertheless, this expends currently limited knowledge regarding the association of the telomere attrition and the disease severity or motor complications in Parkinson’s disease.

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Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation

npj Parkinson s Disease ◽

10.1038/s41531-021-00156-z ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Stefano Romano ◽

George M. Savva ◽

Janis R. Bedarf ◽

Ian G. Charles ◽

Falk Hildebrand ◽

...

Keyword(s):

Parkinson’S Disease ◽

Fatty Acids ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Gut Microbiome ◽

Intestinal Inflammation ◽

Meta Analysis ◽

Gastrointestinal Symptoms ◽

Short Chain Fatty Acids ◽

Inflammatory Status

AbstractThe gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.

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Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease

Molecular Neurodegeneration ◽

10.1186/s13024-021-00427-6 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Velma T. E. Aho ◽

Madelyn C. Houser ◽

Pedro A. B. Pereira ◽

Jianjun Chang ◽

Knut Rudi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Fatty Acids ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Inflammatory Responses ◽

Disease Onset ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Dependent Manner ◽

Chain Fatty Acids

Abstract Background Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD. Methods Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. Results Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex. Conclusions Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.

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The Role of The Gut Microbiome in Parkinson’s Disease

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/08919887211018268 ◽

2021 ◽

Vol 34 (4) ◽

pp. 253-262

Author(s):

Amy Gallop ◽

James Weagley ◽

Saif-ur-Rahman Paracha ◽

George Grossberg

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Symptom Relief ◽

Antibiotic Use ◽

Fecal Microbiota ◽

Fermented Food ◽

Fecal Microbiota Transplant ◽

Disease States ◽

Cord Blood Transplant

The gut microbiota is known to play a role in various disease states through inflammatory, immune and endocrinologic response. Parkinson’s Disease is of particular interest as gastrointestinal involvement is one of the earlier features seen in this disease. This paper examines the relationship between gut microbiota and Parkinson’s Disease, which has a growing body of literature. Inflammation caused by gut dysbiosis is thought to increase a-synuclein aggregation and worsen motor and neurologic symptoms of Parkinson’s disease. We discuss potential treatment and supplementation to modify the microbiota. Some of these treatments require further research before recommendations can be made, such as cord blood transplant, antibiotic use, immunomodulation and fecal microbiota transplant. Other interventions, such as increasing dietary fiber, polyphenol and fermented food intake, can be made with few risks and may have some benefit for symptom relief and speed of disease progression.

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Unravelling the role of gut microbiota in Parkinson’s disease progression: Pathogenic and therapeutic implications

Neuroscience Research ◽

10.1016/j.neures.2021.01.001 ◽

2021 ◽

Author(s):

Linchi Rani ◽

Amal Chandra Mondal

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Disease Progression ◽

Therapeutic Implications

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Salivary caffeine in Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-89168-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Giorgio Leodori ◽

Maria Ilenia De Bartolo ◽

Daniele Belvisi ◽

Alessia Ciogli ◽

Andrea Fabbrini ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

De Novo ◽

Oral Intake ◽

Caffeine Intake ◽

Motor Complications ◽

Disease Rating ◽

Caffeine Metabolism ◽

Movement Disorder Society

AbstractWe aimed to investigate salivary caffeine content, caffeine absorption and metabolism in Parkinson’s disease (PD) and verify whether salivary caffeine can be used as a biomarker of PD. We enrolled 98 PD patients and 92 healthy subjects. Caffeine and its major metabolite, paraxanthine, were measured in saliva samples collected before and 4 h after the oral intake of caffeine (100 mg). We measured caffeine absorption as the normalized increase in caffeine levels, and caffeine metabolism as the paraxanthine/caffeine ratio. The Movement Disorder Society Unified Parkinson's Disease Rating Scale part III, the Hoehn & Yahr, the presence of motor complications, and levodopa equivalent dose (LED) were assessed and correlated with caffeine levels, absorption, and metabolism. The effects of demographic and environmental features possibly influencing caffeine levels were also investigated. Caffeine levels were decreased in patients with moderate/advanced PD, while caffeine levels were normal in patients with early and de-novo PD, unrelated to caffeine intake. Caffeine absorption and metabolism were normal in PD. Decreased salivary caffeine levels in PD were associated with higher disease severity, longer duration, and the presence of motor complications, no significant association was found with LED. Salivary caffeine decrease correlates with PD progression.

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