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      Gut microbiota in Parkinson's disease: Temporal stability and relations to disease progression

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          Abstract

          Background

          Several publications have described differences in cross-sectional comparisons of gut microbiota between patients with Parkinson's disease and control subjects, with considerable variability of the reported differentially abundant taxa. The temporal stability of such microbiota alterations and their relationship to disease progression have not been previously studied with a high-throughput sequencing based approach.

          Methods

          We collected clinical data and stool samples from 64 Parkinson's patients and 64 control subjects twice, on average 2·25 years apart. Disease progression was evaluated based on changes in Unified Parkinson's Disease Rating Scale and Levodopa Equivalent Dose, and microbiota were characterized with 16S rRNA gene amplicon sequencing.

          Findings

          We compared patients to controls, and patients with stable disease to those with faster progression. There were significant differences between microbial communities of patients and controls when corrected for confounders, but not between timepoints. Specific bacterial taxa that differed between patients and controls at both timepoints included several previously reported ones, such as Roseburia, Prevotella and Bifidobacterium. In progression comparisons, differentially abundant taxa were inconsistent across methods and timepoints, but there was some support for a different distribution of enterotypes and a decreased abundance of Prevotella in faster-progressing patients.

          Interpretation

          The previously detected gut microbiota differences between Parkinson's patients and controls persisted after 2 years. While we found some evidence for a connection between microbiota and disease progression, a longer follow-up period is required to confirm these findings.

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          Most cited references23

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Enterotypes in the landscape of gut microbial community composition

            Population stratification is a useful approach towards a better understanding of complex biological problems in human health and well-being. The proposal that such stratification applies to the human gut microbiome, in the form of distinct community composition types, termed “enterotypes”, was met with both excitement and controversy. In view of accumulated data and re-analyses since the original work, we revisit the enterotype concept, discuss different methods of dividing up the landscape of possible microbiome configurations, and put these concepts into a functional, ecological and medical context. As enterotypes are of use in describing the gut microbial community landscape and may become relevant in clinical practice, we aim to reconcile differing views and encourage a balanced application of the concept.
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              Parkinson's disease: a dual‐hit hypothesis

              Accumulating evidence suggests that sporadic Parkinson's disease has a long prodromal period during which several non‐motor features develop, in particular, impairment of olfaction, vagal dysfunction and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexus of the stomach. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (i) nasal, with anterograde progression into the temporal lobe; and (ii) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and, via transsynaptic transmission, reach the preganglionic parasympathetic motor neurones of the vagus nerve. This would allow retrograde transport into the medulla and, from here, into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed, and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sporadic Parkinson's disease is pathogenic access to the brain through the stomach and nose – hence the term ‘dual‐hit’.
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                Author and article information

                Contributors
                Journal
                EBioMedicine
                EBioMedicine
                EBioMedicine
                Elsevier
                2352-3964
                18 June 2019
                June 2019
                18 June 2019
                : 44
                : 691-707
                Affiliations
                [a ]Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, Viikinkaari 5D, P.O. Box 56, 00014 Helsinki, University of Helsinki, Finland
                [b ]Department of Neurology, Helsinki University Hospital, and Department of Neurological Sciences (Neurology), University of Helsinki, Haartmaninkatu 4, 00290 Helsinki, Finland
                [c ]Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland
                Author notes
                [* ]Corresponding author at: Dept. of Neurology, Helsinki University Hospital, Haartmaninkatu 4, 00290 Helsinki, Finland. filip.scheperjans@ 123456hus.fi
                Article
                S2352-3964(19)30372-X
                10.1016/j.ebiom.2019.05.064
                6606744
                31221587
                ebc99bd3-9028-43cc-8ac2-71ca05cf0a0a
                © 2019 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 8 February 2019
                : 30 May 2019
                : 30 May 2019
                Categories
                Research paper

                parkinson's disease,gut microbiota,gut-brain-axis,disease progression

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