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      The Gut Microbiome Alterations and Inflammation-Driven Pathogenesis of Alzheimer’s Disease—a Critical Review

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          Abstract

          One of the most important scientific discoveries of recent years was the disclosure that the intestinal microflora takes part in bidirectional communication between the gut and the brain. Scientists suggest that human gut microflora may even act as the “second brain” and be responsible for neurodegenerative disorders like Alzheimer’s disease (AD). Although human-associated microbial communities are generally stable, they can be altered by common human actions and experiences. Enteric bacteria, commensal, and pathogenic microorganisms, may have a major impact on immune system, brain development, and behavior, as they are able to produce several neurotransmitters and neuromodulators like serotonin, kynurenine, catecholamine, etc., as well as amyloids. However, brain destructive mechanisms, that can lead to dementia and AD, start with the intestinal microbiome dysbiosis, development of local and systemic inflammation, and dysregulation of the gut-brain axis. Increased permeability of the gut epithelial barrier results in invasion of different bacteria, viruses, and their neuroactive products that support neuroinflammatory reactions in the brain. It seems that, inflammatory-infectious hypothesis of AD, with the great role of the gut microbiome, starts to gently push into the shadow the amyloid cascade hypothesis that has dominated for decades. It is strongly postulated that AD may begin in the gut, and is closely related to the imbalance of gut microbiota. This is promising area for therapeutic intervention. Modulation of gut microbiota through personalized diet or beneficial microbiota intervention, alter microbial partners and their products including amyloid protein, will probably become a new treatment for AD.

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          Temporal dynamics of the human vaginal microbiota.

          Elucidating the factors that impinge on the stability of bacterial communities in the vagina may help in predicting the risk of diseases that affect women's health. Here, we describe the temporal dynamics of the composition of vaginal bacterial communities in 32 reproductive-age women over a 16-week period. The analysis revealed the dynamics of five major classes of bacterial communities and showed that some communities change markedly over short time periods, whereas others are relatively stable. Modeling community stability using new quantitative measures indicates that deviation from stability correlates with time in the menstrual cycle, bacterial community composition, and sexual activity. The women studied are healthy; thus, it appears that neither variation in community composition per se nor higher levels of observed diversity (co-dominance) are necessarily indicative of dysbiosis.
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            Short-Term Antibiotic Treatment Has Differing Long-Term Impacts on the Human Throat and Gut Microbiome

            Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment on the human indigenous microbiota are relatively unexplored. Here we studied short- and long-term effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H. pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in samples collected over a four-year period were monitored by analyzing the 16S rRNA gene using 454-based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to prevent subsequent treatment failure and potential spread of antibiotic resistance.
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              Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.

              The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies.
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                Author and article information

                Contributors
                jerzy.leszek@umed.wroc.pl
                Journal
                Mol Neurobiol
                Mol. Neurobiol
                Molecular Neurobiology
                Springer US (New York )
                0893-7648
                1559-1182
                23 June 2018
                23 June 2018
                2019
                : 56
                : 3
                : 1841-1851
                Affiliations
                [1 ]ISNI 0000 0001 1958 0162, GRID grid.413454.3, Laboratory of Virology, Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, , Polish Academy of Sciences, ; Wroclaw, Poland
                [2 ]ISNI 0000 0001 1371 5636, GRID grid.419840.0, Laboratory of Parasitology, , General Karol Kaczkowski Military Institute of Hygiene and Epidemiology, ; Warsaw, Poland
                [3 ]ISNI 0000 0000 9206 2401, GRID grid.267308.8, Department of Psychiatry and Behavioral Sciences, and The Consortium on Aging, , The University of Texas Health Science Center at Houston, ; Houston, TX USA
                [4 ]ISNI 0000 0001 1090 049X, GRID grid.4495.c, Department of Family Medicine, , Wroclaw Medical University, ; Wroclaw, Poland
                [5 ]ISNI 0000 0001 1958 0162, GRID grid.413454.3, Laboratory of Medical Microbiology, Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, , Polish Academy of Sciences, ; Wroclaw, Poland
                [6 ]ISNI 0000 0001 1090 049X, GRID grid.4495.c, Department of Psychiatry, , Wroclaw Medical University, ; Wroclaw, Poland
                Author information
                http://orcid.org/0000-0002-2316-2470
                Article
                1188
                10.1007/s12035-018-1188-4
                6394610
                29936690
                56484632-c132-46be-a85c-de7298beb648
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 19 April 2018
                : 7 June 2018
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                © Springer Science+Business Media, LLC, part of Springer Nature 2019

                Neurosciences
                alzheimer’s disease,gut microbiome,neuroinflammation,microbial amyloid,therapeutic intervention

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