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Int. J. Mol. Sci. 2018, 19(6), 1689; https://doi.org/10.3390/ijms19061689

Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease

1
Pharmacology Building, Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
2
APC Microbiome Ireland, University College Cork, T12YT20 Cork, Ireland
*
Author to whom correspondence should be addressed.
Received: 3 May 2018 / Revised: 31 May 2018 / Accepted: 3 June 2018 / Published: 6 June 2018
(This article belongs to the Special Issue Molecular Research on Neurodegenerative Diseases)
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Abstract

Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. The highly bidirectional communication between the brain and the gut is markedly influenced by the microbiome through integrated immunological, neuroendocrine and neurological processes. The gut microbiota and its relevant metabolites interact with the host via a series of biochemical and functional inputs, thereby affecting host homeostasis and health. Indeed, a dysregulated microbiota-gut-brain axis in PD might lie at the basis of gastrointestinal dysfunctions which predominantly emerge many years prior to the diagnosis, corroborating the theory that the pathological process is spread from the gut to the brain. Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs primarily found in microorganisms and a dysregulation in their signaling may be implicated in α-synucleinopathy, such as PD. An overstimulation of the innate immune system due to gut dysbiosis and/or small intestinal bacterial overgrowth, together with higher intestinal barrier permeability, may provoke local and systemic inflammation as well as enteric neuroglial activation, ultimately triggering the development of alpha-synuclein pathology. In this review, we provide the current knowledge regarding the relationship between the microbiota-gut–brain axis and TLRs in PD. A better understanding of the dialogue sustained by the microbiota-gut-brain axis and innate immunity via TLR signaling should bring interesting insights in the pathophysiology of PD and provide novel dietary and/or therapeutic measures aimed at shaping the gut microbiota composition, improving the intestinal epithelial barrier function and balancing the innate immune response in PD patients, in order to influence the early phases of the following neurodegenerative cascade. View Full-Text
Keywords: enteric microbiota; brain-gut axis; Parkinson’s disease; toll-like receptors; innate immunity; central nervous system; enteric nervous system; gastrointestinal dysfunctions; probiotics; pharmacological treatment; α-synuclein; gut dysbiosis; neurons; microglia; glial cells; intestinal barrier permeability enteric microbiota; brain-gut axis; Parkinson’s disease; toll-like receptors; innate immunity; central nervous system; enteric nervous system; gastrointestinal dysfunctions; probiotics; pharmacological treatment; α-synuclein; gut dysbiosis; neurons; microglia; glial cells; intestinal barrier permeability
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Caputi, V.; Giron, M.C. Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease. Int. J. Mol. Sci. 2018, 19, 1689.

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