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Diet in Parkinson's Disease: Critical Role for the Microbiome.

ABSTRACT: Background: Parkinson's disease (PD) is the most common movement disorder affecting up to 1% of the population above the age of 60 and 4-5% of those above the age of 85. Little progress has been made on efforts to prevent disease development or halt disease progression. Diet has emerged as a potential factor that may prevent the development or slow the progression of PD. In this review, we discuss evidence for a role for the intestinal microbiome in PD and how diet-associated changes in the microbiome may be a viable approach to prevent or modify disease progression. Methods: We reviewed studies demonstrating that dietary components/foods were related to risk for PD. We reviewed evidence for the dysregulated intestinal microbiome in PD patients including abnormal shifts in the intestinal microbiota composition (i.e., dysbiosis) characterized by a loss of short chain fatty acid (SCFA) bacteria and increased lipopolysaccharide (LPS) bacteria. We also examined several candidate mechanisms by which the microbiota can influence PD including the NLRP3 inflammasome, insulin resistance, mitochondrial function, vagal nerve signaling. Results: The PD-associated microbiome is associated with decreased production of SCFA and increased LPS and it is believed that these changes may contribute to the development or exacerbation of PD. Diet robustly impacts the intestinal microbiome and the Western diet is associated with increased risk for PD whereas the Mediterranean diet (including high intake of dietary fiber) decreases PD risk. Mechanistically this may be the consequence of changes in the relative abundance of SCFA-producing or LPS-containing bacteria in the intestinal microbiome with effects on intestinal barrier function, endotoxemia (i.e., systemic LPS), NLRP3 inflammasome activation, insulin resistance, and mitochondrial dysfunction, and the production of factors such as glucagon like peptide 1 (GLP-1) and brain derived neurotrophic factor (BDNF) as well as intestinal gluconeogenesis. Conclusions: This review summarizes a model of microbiota-gut-brain-axis regulation of neuroinflammation in PD including several new mechanisms. We conclude with the need for clinical trials in PD patients to test this model for beneficial effects of Mediterranean based high fiber diets.

SUBMITTER: Jackson A

PROVIDER: S-EPMC6915094 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThere is mounting evidence for a connection between the gut and Parkinson's disease (PD). Dysbiosis of gut microbiota could explain several features of PD.ObjectiveThe objective of this study was to determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research.MethodsA total of 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways.ResultsIndependent microbial signatures were detected for PD (P = 4E-5), participants' region of residence within the United States (P = 3E-3), age (P = 0.03), sex (P = 1E-3), and dietary fruits/vegetables (P = 0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P = 4E-4), anticholinergics (P = 5E-3), and possibly carbidopa/levodopa (P = 0.05). We found significantly altered abundances of the Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways, including the metabolism of plant-derived compounds and xenobiotics degradation.ConclusionPD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. © 2017 International Parkinson and Movement Disorder Society.

Project description:Approximately half of patients with Parkinson's disease (PD) suffer from unintentional weight loss and are underweight, complicating the clinical course of PD patients. Gut microbiota alteration has been proven to be associated with PD, and recent studies have shown that gut microbiota could lead to muscle wasting, implying a possible role of gut microbiota in underweight PD. In this study, we aimed to (1) investigate the mechanism underlying underweight in PD patients with respect to gut microbiota and (2) estimate the extent to which gut microbiota may mediate PD-related underweight through mediation analysis. The data were adapted from Hill-Burns et al., in which 330 participants (199 PD, 131 controls) were enrolled in the study. Fecal samples were collected from participants for microbiome analysis. 16S rRNA gene sequence data were processed using DADA2. Mediation analysis was performed to quantify the effect of intestinal microbial alteration on the causal effect of PD on underweight and to identify the key bacteria that significantly mediated PD-related underweight. The results showed that the PD group had significantly more underweight patients (body mass index (BMI) < 18.5) after controlling for age and sex. Ten genera and four species were significantly different in relative abundance between the underweight and non-underweight individuals in the PD group. Mediation analysis showed that 42.29% and 37.91% of the effect of PD on underweight was mediated through intestinal microbial alterations at the genus and species levels, respectively. Five genera (Agathobacter, Eisenbergiella, Fusicatenibacter, Roseburia, Ruminococcaceae_UCG_013) showed significant mediation effects. In conclusion, we found that up to 42.29% of underweight PD cases are mediated by gut microbiota, with increased pro-inflammatory bacteria and decreased SCFA-producing bacteria, which indicates that the pro-inflammatory state, disturbance of metabolism, and interference of appetite regulation may be involved in the mechanism of underweight PD.

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Diet in Parkinson's Disease: Critical Role for the Microbiome.

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