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      Global research trends in microbiome-gut-brain axis during 2009–2018: a bibliometric and visualized study

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          Abstract

          Background

          The pathways and mechanism by which associations between the gut microbiome and the brain, termed the microbiome-gut-brain axis (MGBA), are manifest but remain to be fully elucidated. This study aims to use bibliometric analysis to estimate the global activity within this rapidly developing field and to identify particular areas of focus that are of current relevance to the MGBA during the last decade (2009–2018).

          Methods

          The current study uses the Scopus for data collection. We used the key terms “microbiome-gut-brain axis” and its synonyms because we are concerned with MGBA per se as a new concept in research rather than related topics. A VOSviewer version 1.6.11 was used to visualize collaboration pattern between countries and authors, and evolving research topics by analysis of the term co-occurrence in the title and abstract of publications.

          Results

          Between 2009 and 2018, there were 51,504 published documents related to the microbiome, including 1713 articles related to the MGBA: 829 (48.4%) original articles, 658(38.4%) reviews, and 226 (13.2%) other articles such as notes, editorials or letters. The USA took the first place with 385 appearances, followed by Ireland ( n = 161), China ( n = 155), and Canada ( n = 144).The overall citation h-index was 106, and the countries with the highest h-index values were the USA (69), Ireland (58), and Canada (43). The cluster analysis demonstrated that the dominant fields of the MGBA include four clusters with four research directions: “modeling MGBA in animal systems”, “interplay between the gut microbiota and the immune system”, “irritable bowel syndrome related to gut microbiota”, and “neurodegenerative diseases related to gut microbiota”.

          Conclusions

          This study demonstrates that the research on the MGBA has been becoming progressively more extensive at global level over the past 10 years. Overall, our study found that a large amount of work on MGBA focused on immunomodulation, irritable bowel syndrome, and neurodevelopmental disorders. Despite considerable progress illustrating the communication between the gut microbiome and the brain over the past 10 years, many issues remain about their relevance for therapeutic intervention of many diseases.

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          Most cited references55

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          The gut microbiota influences blood-brain barrier permeability in mice.

          Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to regulate barrier function in endothelial tissues. Exposure of germ-free adult mice to a pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. Our results suggest that gut microbiota-BBB communication is initiated during gestation and propagated throughout life.
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            Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression.

            The concept that intestinal microbial composition not only affects the health of the gut, but also influences centrally-mediated systems involved in mood, is supported by a growing body of literature. Despite the emergent interest in brain-gut communication and its possible role in the pathogenesis of psychiatric disorders such as depression, particularly subtypes with accompanying gastrointestinal (GI) symptoms, there are few studies dedicated to the search for therapeutic solutions that address both central and peripheral facets of these illnesses. This study aims to assess the potential benefits of the probiotic Bifidobacterium infantis in the rat maternal separation (MS) model, a paradigm that has proven to be of value in the study of stress-related GI and mood disorders. MS adult rat offsprings were chronically treated with bifidobacteria or citalopram and subjected to the forced swim test (FST) to assess motivational state. Cytokine concentrations in stimulated whole blood samples, monoamine levels in the brain, and central and peripheral hypothalamic-pituitary-adrenal (HPA) axis measures were also analysed. MS reduced swim behavior and increased immobility in the FST, decreased noradrenaline (NA) content in the brain, and enhanced peripheral interleukin (IL)-6 release and amygdala corticotrophin-releasing factor mRNA levels. Probiotic treatment resulted in normalization of the immune response, reversal of behavioral deficits, and restoration of basal NA concentrations in the brainstem. These findings point to a more influential role for bifidobacteria in neural function, and suggest that probiotics may have broader therapeutic applications than previously considered. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
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              Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses.

              Adverse early life events are associated with a maladaptive stress response system and might increase the vulnerability to disease in later life. Several disorders have been associated with early life stress, ranging from depression to irritable bowel syndrome. This makes the identification of the neurobiological substrates that are affected by adverse experiences in early life invaluable. The purpose of this study was to assess the effect of early life stress on the brain-gut axis. Male rat pups were stressed by separating them from their mothers for 3 hours daily between postnatal days 2-12. The control group was left undisturbed with their mothers. Behavior, immune response, stress sensitivity, visceral sensation, and fecal microbiota were analyzed. The early life stress increased the number of fecal boli in response to a novel stress. Plasma corticosterone was increased in the maternally separated animals. An increase in the systemic immune response was noted in the stressed animals after an in vitro lipopolysaccharide challenge. Increased visceral sensation was seen in the stressed group. There was an alteration of the fecal microbiota when compared with the control group. These results show that this form of early life stress results in an altered brain-gut axis and is therefore an important model for investigating potential mechanistic insights into stress-related disorders including depression and IBS.
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                Author and article information

                Contributors
                saedzyoud@yahoo.com , saedzyoud@najah.edu
                simonsmale1969@gmail.com
                stephen.waring@york.nhs.uk
                waleedsweileh@yahoo.com
                samahjabi@yahoo.com
                Journal
                BMC Gastroenterol
                BMC Gastroenterol
                BMC Gastroenterology
                BioMed Central (London )
                1471-230X
                30 August 2019
                30 August 2019
                2019
                : 19
                : 158
                Affiliations
                [1 ]ISNI 0000 0004 0631 5695, GRID grid.11942.3f, Poison Control and Drug Information Center (PCDIC), College of Medicine and Health Sciences, , An-Najah National University, ; Nablus, 44839 Palestine
                [2 ]ISNI 0000 0004 0631 5695, GRID grid.11942.3f, Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, , An-Najah National University, ; Nablus, 44839 Palestine
                [3 ]ISNI 0000 0004 0631 5695, GRID grid.11942.3f, Clinical Research Centre, , An-Najah National University Hospital, ; Nablus, 44839 Palestine
                [4 ]GRID grid.439905.2, Department of Gastroenterology, York Hospital, , York Teaching Hospital NHS Foundation Trust, ; Wigginton Road, York, YO31 8HE UK
                [5 ]GRID grid.439905.2, Acute Medical Unit, , York Teaching Hospitals NHS Foundation Trust, ; Wigginton Road, York, YO31 8HE UK
                [6 ]ISNI 0000 0004 0631 5695, GRID grid.11942.3f, Department of Pharmacology and Toxicology, College of Medicine and Health Sciences, , An-Najah National University, ; Nablus, 44839 Palestine
                Author information
                http://orcid.org/0000-0002-7369-2058
                Article
                1076
                10.1186/s12876-019-1076-z
                6716890
                31470803
                f454f4b0-a6d6-407f-9888-07dbe28316a6
                © The Author(s). 2019

                Open AccessThis 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. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 29 May 2019
                : 23 August 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Gastroenterology & Hepatology
                gut microbiota,gut microbiome-brain axis,microbiome,bibliometric,scopus

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