The Oral and Fecal Microbiota in a Canadian Cohort of Alzheimer's Disease.

BACKGROUND: Despite decades of research, our understanding of Alzheimer's disease (AD) etiology remains incomplete. In recent years, appreciation has grown for potential roles for the microbiota in shaping neurological health. OBJECTIVE: This study aimed to examine associations between the microbiota and AD in a human cross-sectional cohort. METHODS: Forty-five AD patients and 54 matched controls were recruited in Vancouver, Canada. Fecal and oral samples underwent 16S microbiota sequencing. A wide array of demographic and clinical data were collected. Differences between participant groups were assessed, and associations between microbes and clinical variables were examined within the AD population. RESULTS: The gut microbiota of AD patients displayed lower diversity relative to controls, although taxonomic differences were sparse. In contrast, the AD oral microbiota displayed higher diversity, with several taxonomic differences relative to controls, including a lower abundance of the families Streptococcaceae and Actinomycetaceae, and a higher abundance of Weeksellaceae, among others. The periodontitis-associated oral microbe Porphyromonas gingivalis was 5 times more prevalent among patients. No significant associations between gut or oral microbes and cognition were detected, but several correlations existed between microbes and mood disorders and BMI among patients, including a strong positive correlation between Alphaproteobacteria and depression score. CONCLUSION: The gut microbiota of AD patients was not overtly different from controls, although it displayed lower diversity, an overall marker of microbiota health. The oral microbiota did display marked differences. Cognition was not associated with a microbial signature, but other relevant AD factors including mood and BMI did demonstrate an association.

MIND and Mediterranean Diets Associated with Later Onset of Parkinson's Disease.

BACKGROUND: The MIND diet has been linked with prevention of Alzheimer's disease and cognitive decline but has not been fully assessed in the context of Parkinson's disease (PD). The objective of the present study was to determine whether MIND diet adherence is associated with the age of Parkinson's disease onset in a manner superior to that of the Mediterranean diet. METHODS: Food Frequency Questionnaires from 167 participants with PD and 119 controls were scored for MIND and 2 versions of Mediterranean diet adherence. Scores were compared between sex and disease subgroups, and PD diet adherence was correlated with age at onset using univariate and multivariate linear models. RESULTS: The female subgroup adhered more closely to the MIND diet than the male subgroup, and diet scores were not modified by disease status. Later age of onset correlated most strongly with MIND diet adherence in the female subgroup, corresponding to differences of up to 17.4 years (P < 0.001) between low and high dietary tertiles. Greek Mediterranean adherence was also significantly associated with later PD onset across all models (P = 0.05-0.03). Conversely, only Greek Mediterranean diet adherence remained correlated with later onset across all models in men, with differences of up to 8.4 years (P = 0.002). CONCLUSIONS: This cross-sectional study found a strong correlation between age of onset of PD and dietary habits, suggesting that nutritional strategies may be an effective tool to delay PD onset. Further studies may help to elucidate potential nutrition-related sex-specific pathophysiological mechanisms and differential prevalence rates in PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Gut Mycobiome in Parkinson's Disease.

The gut microbiome has been increasingly implicated in Parkinson's disease (PD); however, most existing studies employ bacterial-specific sequencing, and have not investigated non-bacterial microbiome constituents. Here, we use fungal-specific internal transcribed spacer (ITS)-2 amplicon sequencing in a cross-sectional PD cohort to investigate associations between the fungal gut microbiome and PD. Fungal load among participants was extremely low, and genera identified were almost exclusively of proposed dietary or environmental origin. We observed significantly lower fungal DNA relative to bacterial DNA among PD patients. No fungi differed in abundance between patients and controls, nor were any associated with motor, cognitive, or gastrointestinal features among patients.

Microbiota Composition and Metabolism Are Associated With Gut Function in Parkinson's Disease.

BACKGROUND: Parkinson's disease is characterized by a high burden of gastrointestinal comorbidities, especially constipation and reduced colonic transit time, and by gut microbiota alterations. The diverse metabolites produced by the microbiota are broadly relevant to host health. How microbiota composition and metabolism relate to gastrointestinal function in Parkinson's disease is largely unknown. The objectives of the current study were to assesses associations between microbiota composition, stool consistency, constipation, and systemic microbial metabolites in Parkinson's disease to better understand how intestinal microbes contribute to gastrointestinal disturbances commonly observed in patients. METHODS: Three hundred participants (197 Parkinson's patients and 103 controls) were recruited for this cross-sectional cohort study. Participants supplied fecal samples for microbiota sequencing (n = 300) and serum for untargeted metabolomics (n = 125). Data were collected on motor and nonmotor Parkinson's symptoms, medications, diet, and demographics. RESULTS: Significant microbiota taxonomic differences were observed in Parkinson's patients, even when controlling for gastrointestinal function. Parkinson's microbiota was characterized by reduced carbohydrate fermentation and butyrate synthesis capacity and increased proteolytic fermentation and production of deleterious amino acid metabolites, including p-cresol and phenylacetylglutamine. Taxonomic shifts and elevated proteolytic metabolites were strongly associated with stool consistency (a proxy for colonic transit time) and constipation among patients. CONCLUSIONS: Compositional and metabolic alterations in the Parkinson's microbiota are highly associated with gut function, suggesting plausible mechanistic links between altered bacterial metabolism and reduced gut health in this disease. The systemic detection of elevated deleterious proteolytic microbial metabolites in Parkinson's serum suggests a mechanism whereby microbiota dysbiosis contributes to disease etiology and pathophysiology. © 2020 International Parkinson and Movement Disorder Society.

High yield primary microglial cultures using granulocyte macrophage-colony stimulating factor from embryonic murine cerebral cortical tissue.

BACKGROUND: Microglia play vital roles in neurotrophic support and modulating immune or inflammatory responses to pathogens or damage/stressors during disease. This study describes the ability to establish large numbers of microglia from embryonic tissues with the addition of granulocyte-macrophage stimulating factor (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo as well as their responses to inflammatory mediators. METHOD: Microglia were seeded from a primary embryonic mixed cortical suspension with the addition of GM-CSF. Microglial expression of CD45, CD11b, CD11c, MHC class I and II, CD40, CD80, and CD86 was analyzed by flow cytometry and compared to those isolated using different culture methods and to the BV-2 cell line. GM-CSF microglia immunoreactivity and cytokine production was examined in response to lipopolysaccharide (LPS) and interferon-γ (IFN-γ). RESULTS: Our results demonstrate GM-CSF addition during microglial culture yields higher cell numbers with greater purity than conventionally cultured primary microglia. We found that the expression of immune markers by GM-CSF microglia more closely resemble adult microglia than other methods or an immortalized BV-2 cell line. Primary differences amongst the different groups were reflected in their levels of CD39, CD86 and MHC class I expression. GM-CSF microglia produce CCL2, tumor necrosis factor-α, IL-6 and IL-10 following exposure to LPS and alter costimulatory marker expression in response to LPS or IFN-γ. Notably, GM-CSF microglia were often more responsive than the commonly used BV-2 cell line which produced negligible IL-10. CONCLUSION: GM-CSF cultured microglia closely model the phenotype of adult microglia examined ex vivo. GM-CSF microglia are robust in their responses to inflammatory stimuli, altering immune markers including Iba-1 and expressing an array of cytokines characteristic of both pro-inflammatory and reparative processes. Consequently, the addition of GM-CSF for the culturing of primary microglia serves as a valuable method to increase the potential for studying microglial function ex vivo.