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      Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health

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          ABSTRACT

          The human gastrointestinal (gut) microbiota comprises diverse and dynamic populations of bacteria, archaea, viruses, fungi, and protozoa, coexisting in a mutualistic relationship with the host. When intestinal homeostasis is perturbed, the function of the gastrointestinal tract and other organ systems, including the brain, can be compromised. The gut microbiota is proposed to contribute to blood-brain barrier disruption and the pathogenesis of neurodegenerative diseases. While progress is being made, a better understanding of interactions between gut microbes and host cells, and the impact these have on signaling from gut to brain is now required. In this review, we summarise current evidence of the impact gut microbes and their metabolites have on blood-brain barrier integrity and brain function, and the communication networks between the gastrointestinal tract and brain, which they may modulate. We also discuss the potential of microbiota modulation strategies as therapeutic tools for promoting and restoring brain health.

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          Most cited references145

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          Stages in the development of Parkinson's disease-related pathology.

          The synucleinopathy, idiopathic Parkinson's disease, is a multisystem disorder that involves only a few predisposed nerve cell types in specific regions of the human nervous system. The intracerebral formation of abnormal proteinaceous Lewy bodies and Lewy neurites begins at defined induction sites and advances in a topographically predictable sequence. As the disease progresses, components of the autonomic, limbic, and somatomotor systems become particularly badly damaged. During presymptomatic stages 1-2, inclusion body pathology is confined to the medulla oblongata/pontine tegmentum and olfactory bulb/anterior olfactory nucleus. In stages 3-4, the substantia nigra and other nuclear grays of the midbrain and forebrain become the focus of initially slight and, then, severe pathological changes. At this point, most individuals probably cross the threshold to the symptomatic phase of the illness. In the end-stages 5-6, the process enters the mature neocortex, and the disease manifests itself in all of its clinical dimensions.
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            Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial.

            Ulcerative colitis (UC) is difficult to treat, and standard therapy does not always induce remission. Fecal microbiota transplantation (FMT) is an alternative approach that induced remission in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled randomized trial.
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              Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism.

              Inflammation, a common denominator among the diverse list of neurodegenerative diseases, has recently been implicated as a critical mechanism responsible for the progressive nature of neurodegeneration. Microglia are the resident innate immune cells in the central nervous system and produce a barrage of factors (IL-1, TNFalpha, NO, PGE2, superoxide) that are toxic to neurons. Evidence supports that the unregulated activation of microglia in response to environmental toxins, endogenous proteins, and neuronal death results in the production of toxic factors that propagate neuronal injury. In the following review, we discuss the common thread of microglial activation across numerous neurodegenerative diseases, define current perceptions of how microglia are damaging neurons, and explain how the microglial response to neuronal damage results in a self-propelling cycle of neuron death.
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                Author and article information

                Journal
                Gut Microbes
                Gut Microbes
                KGMI
                kgmi20
                Gut Microbes
                Taylor & Francis
                1949-0976
                1949-0984
                2020
                1 August 2019
                1 August 2019
                : 11
                : 2
                : 135-157
                Affiliations
                [a ]Gut Microbes and Health Research Programme, Quadram Institute Bioscience , Norwich, UK
                [b ]Norwich Medical School, University of East Anglia , Norwich, UK
                Author notes
                CONTACT Simon R. Carding Simon.Carding@ 123456Quadram.ac.uk Gut Microbes and Health Research Programme, Quadram Institute Bioscience, Norwich Research Park , Norwich NR4 7UA, UK
                [*]

                Equal contribution

                Article
                1638722
                10.1080/19490976.2019.1638722
                7053956
                31368397
                700fe7df-5212-4dd8-94e3-49acb1b666d1
                © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 March 2019
                : 22 May 2019
                : 26 June 2019
                Page count
                Figures: 2, Tables: 1, References: 223, Pages: 23
                Funding
                Funded by: Biotechnology and Biological Sciences Research Council 10.13039/501100000268
                Award ID: BB/J004529/1
                Funded by: Biotechnology and Biological Sciences Research Council 10.13039/501100000268
                Award ID: BB/R012490/1
                Funded by: Biotechnology and Biological Sciences Research Council 10.13039/501100000268
                Award ID: BBS/E/F000PR10355
                Funded by: Fundación Alfonso Martín Escudero 10.13039/100008052
                Award ID: Fellowship
                This work was supported by the Biotechnology and Biological Sciences Research Council [BB/J004529/1, BB/and BBS/E/F000PR10355] and Fundación Alfonso Martín Escudero [Postdoctoral Fellowship].
                Categories
                Review

                Microbiology & Virology
                microbiota,gut-brain axis,metabolites,blood-brain barrier
                Microbiology & Virology
                microbiota, gut-brain axis, metabolites, blood-brain barrier

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