Dataset Information

Parkinson's Disease: A Comprehensive Analysis of Fungi and Bacteria in Brain Tissue.

ABSTRACT: Parkinson's disease (PD) is characterized by motor disorders and the destruction of dopaminergic neurons in the substantia nigra pars compacta. In addition to motor disability, many patients with PD present a spectrum of clinical symptoms, including cognitive decline, psychiatric alterations, loss of smell and bladder dysfunction, among others. Neuroinflammation is one of the most salient features of PD, but the nature of the trigger remains unknown. A plausible mechanism to explain inflammation and the range of clinical symptoms in these patients is the presence of systemic microbial infection. Accordingly, the present study provides extensive evidence for the existence of mixed microbial infections in the central nervous system (CNS) of patients with PD. Assessment of CNS sections by immunohistochemistry using specific antibodies revealed the presence of both fungi and bacteria. Moreover, different regions of the CNS were positive for a variety of microbial morphologies, suggesting infection by a number of microorganisms. Identification of specific fungal and bacterial species in different CNS regions from six PD patients was accomplished using nested PCR analysis and next-generation sequencing, providing compelling evidence of polymicrobial infections in the CNS of PD. Most of the fungal species identified belong to the genera Botrytis, Candida, Fusarium and Malassezia. Some relevant bacterial genera were Streptococcus and Pseudomonas, with most bacterial species belonging to the phyla Actinobacteria and Proteobacteria. Interestingly, we noted similarities and differences between the microbiota present in the CNS of patients with PD and that in other neurodegenerative diseases. Overall, our observations lend strong support to the concept that mixed microbial infections contribute to or are a risk factor for the neuropathology of PD. Importantly, these results provide the basis for effective treatments of this disease using already approved and safe antimicrobial therapeutics.

SUBMITTER: Pisa D

PROVIDER: S-EPMC7053320 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Parkinson's Disease: A Comprehensive Analysis of Fungi and Bacteria in Brain Tissue.

Pisa Diana D Alonso Ruth R Carrasco Luis L

International journal of biological sciences 20200210 7

Parkinson's disease (PD) is characterized by motor disorders and the destruction of dopaminergic neurons in the substantia nigra pars compacta. In addition to motor disability, many patients with PD present a spectrum of clinical symptoms, including cognitive decline, psychiatric alterations, loss of smell and bladder dysfunction, among others. Neuroinflammation is one of the most salient features of PD, but the nature of the trigger remains unknown. A plausible mechanism to explain inflammation ...[more]

PMID: 32174790

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Project description:Parkinson’s disease is second most prevalent neurodegenerative disorder. Parkinson’s disease is hypothesized to be caused by a multifaceted interplay between genetic and environmental factors. We profiled the DNA methylation using the frontal lobe from people who died from Parkinson’s disease and compared them with age-, and sex-matched controls. We hypothesized that the complex regulation of DNA methylation and metabolome leads to deficits that cause irregular motor function among Parkinson’s disease subjects and the metabolomic disparities may reflect the effect of these complex interactions. Herein, we aim to integrate quantitative metabolomics and DNA methylation of brain tissue from primary motor cortex (Brodmann area 4) from Parkinson’s disease sufferers to better understand the biochemistry associated with the onset of the disease. Parkinson’s disease (PD) is second most prevalent neurodegenerative disorder following Alzheimer’s disease. Parkinson’s disease is hypothesized to be caused by a multifaceted interplay between genetic and environmental factors. Herein, and for the first time, we describe the integration of metabolomics and epigenetics (genome-wide DNA methylation; epimetabolomics) to profile the frontal lobe from people who died from PD and compared them with age-, and sex-matched controls. We identified 48 metabolites to be at significantly different concentrations (FDR q<0.05), 4,313 differentially methylated sites [5'-C-phosphate-G-3' (CpGs)] (FDR q<0.05) and increased DNA methylation age in the primary motor cortex of people who died from PD. We identified Primary bile acid biosynthesis as the major biochemical pathway to be perturbed in the frontal lobe of PD sufferers, and the metabolite taurine (p-value = 5.91E-06) as being positively correlated with CpG cg14286187 (SLC25A27; CYP39A1) (FDR q = 0.002), highlighting previously unreported biochemical changes associated with PD pathogenesis. In this novel multi-omics study, we identify regulatory mechanisms which we believe warrant future translational investigation and central biomarkers of PD which require further validation in more accessible biomatrices.

Dataset Information

Parkinson's Disease: A Comprehensive Analysis of Fungi and Bacteria in Brain Tissue.

Publications

Parkinson's Disease: A Comprehensive Analysis of Fungi and Bacteria in Brain Tissue.

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