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      Gut-Brain-Microbiota Axis: Antibiotics and Functional Gastrointestinal Disorders

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          Abstract

          Gut microbiota composition and function are major areas of research for functional gastrointestinal disorders. There is a connection between gastrointestinal tract and central nervous system and this is mediated by neurotransmitters, inflammatory cytokines, the vagus nerve and the hypothalamic-pituitary-adrenal axis. Functional gastrointestinal disorders are prevalent diseases affecting more than one third of the population. The etiology of these disorders is not clarified. Visceral hyperalgesia is the main hypothesis for explaining clinical symptoms, however gut-brain axis disorder is a new terminology for functional disorders. In this review, microbiota-gut-brain axis connection pathways and related disorders are discussed. Antibiotics are widely used in developed countries and recent evidence indicates antibiotic-induced dysbiosis as an important factor for functional disorders. Antibiotics exert negative effects on gut microbiota composition and functions. Antibiotic-induced dysbiosis is a major factor for occurrence of post-infectious irritable bowel syndrome. Cognitive and mood disorders are also frequent in functional gastrointestinal disorders. Animal and human trials show strong evidence for the causal relationship between gut microbiota and brain functions. Therapeutic implications of these newly defined pathogenic pathways are also discussed.

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          Most cited references103

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          The Microbiota-Gut-Brain Axis

          The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
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            Gut microbiota, metabolites and host immunity.

            The microbiota - the collection of microorganisms that live within and on all mammals - provides crucial signals for the development and function of the immune system. Increased availability of technologies that profile microbial communities is facilitating the entry of many immunologists into the evolving field of host-microbiota studies. The microbial communities, their metabolites and components are not only necessary for immune homeostasis, they also influence the susceptibility of the host to many immune-mediated diseases and disorders. In this Review, we discuss technological and computational approaches for investigating the microbiome, as well as recent advances in our understanding of host immunity and microbial mutualism with a focus on specific microbial metabolites, bacterial components and the immune system.
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              Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease.

              The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                27 January 2021
                February 2021
                : 13
                : 2
                : 389
                Affiliations
                [1 ]Department of Gastroenterology, Faculty of Medicine, Gazi University, 06570 Ankara, Turkey
                [2 ]Department of Pharmaceutical Microbiology, Faculty of Pharmacy, HacettepeUniversity, Sıhhiye, 06110 Ankara, Turkey; cerenozkul@ 123456hacettepe.edu.tr
                [3 ]Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, 06330 Ankara, Turkey; esrak@ 123456gazi.edu.tr
                [4 ]Department of Nutrition and Dietetics, Faculty of Health Science, Gazi University, Beşevler, 06560 Ankara, Turkey; sgbilici@ 123456gazi.edu.tr
                [5 ]Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, 8330507 Santiago, Chile; eduardo.sobarzo@ 123456ucentral.cl
                [6 ]Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
                [7 ]Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Naples, Italy
                Author notes
                [* ]Correspondence: tkarakan@ 123456gmail.com (T.K.); rafcapas@ 123456unina.it (R.C.); Tel.: +90-505-319-2257 (T.K.); +39-081-678664 (R.C.)
                Author information
                https://orcid.org/0000-0003-1561-8789
                https://orcid.org/0000-0002-0921-5863
                https://orcid.org/0000-0002-5829-7869
                https://orcid.org/0000-0002-2790-2544
                https://orcid.org/0000-0002-3335-1822
                Article
                nutrients-13-00389
                10.3390/nu13020389
                7910879
                33513791
                13b5e287-389f-4d68-8994-3ab8bf419be0
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 November 2020
                : 23 January 2021
                Categories
                Review

                Nutrition & Dietetics
                gut microbiota,gut microbiome,gut-brain axis,functional bowel disorders,irritable bowel syndrome,antibiotics,probiotics

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