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      The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into “Old” Diseases

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          Abstract

          The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota—depending on their composition—have disease-promoting effects but can also possess protective properties. This review focuses on disorders of metabolic syndrome, with special regard to obesity as a prequel to type 2 diabetes, type 2 diabetes itself, and type 1 diabetes. In all these conditions, differences in the composition of the gut microbiota in comparison to healthy people have been reported. Mechanisms of the interaction between microbiota and host that have been characterized thus far include an increase in energy harvest, modulation of free fatty acids—especially butyrate—of bile acids, lipopolysaccharides, gamma-aminobutyric acid (GABA), an impact on toll-like receptors, the endocannabinoid system and “metabolic endotoxinemia” as well as “metabolic infection.” This review will also address the influence of already established therapies for metabolic syndrome and diabetes on the microbiota and the present state of attempts to alter the gut microbiota as a therapeutic strategy.

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          Most cited references60

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          Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells.

          Commensal microbes can have a substantial impact on autoimmune disorders, but the underlying molecular and cellular mechanisms remain largely unexplored. We report that autoimmune arthritis was strongly attenuated in the K/BxN mouse model under germ-free (GF) conditions, accompanied by reductions in serum autoantibody titers, splenic autoantibody-secreting cells, germinal centers, and the splenic T helper 17 (Th17) cell population. Neutralization of interleukin-17 prevented arthritis development in specific-pathogen-free K/BxN mice resulting from a direct effect of this cytokine on B cells to inhibit germinal center formation. The systemic deficiencies of the GF animals reflected a loss of Th17 cells from the small intestinal lamina propria. Introduction of a single gut-residing species, segmented filamentous bacteria, into GF animals reinstated the lamina propria Th17 cell compartment and production of autoantibodies, and arthritis rapidly ensued. Thus, a single commensal microbe, via its ability to promote a specific Th cell subset, can drive an autoimmune disease. Copyright 2010 Elsevier Inc. All rights reserved.
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            Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition

            The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as γ-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.
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              Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"?

              J V Neel (1962)
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                Author and article information

                Journal
                Med Sci (Basel)
                Med Sci (Basel)
                medsci
                Medical Sciences
                MDPI
                2076-3271
                17 April 2018
                June 2018
                : 6
                : 2
                : 32
                Affiliations
                [1 ]Division of Endocrinology and Metabolism, Thuringia Clinic Saalfeld “Georgius Agricola”, Department of Internal Medicine II, Teaching Hospital of the University of Jena, Rainweg 68, D-07318 Saalfeld/Saale, Germany
                [2 ]Division of Gastroenterology, Thuringia Clinic Saalfeld “Georgius Agricola”, Department of Internal Medicine II, Teaching Hospital of the University of Jena, Rainweg 68, D-07318 Saalfeld/Saale, Germany; pkonturek@ 123456thueringen-kliniken.de
                Author notes
                [* ]Correspondence: iharsch@ 123456thueringen-kliniken.de ; Tel.: +49-(0)3671-541-569; Fax: +49-(0)3671-541-403
                Article
                medsci-06-00032
                10.3390/medsci6020032
                6024804
                29673211
                ba69b416-823b-4be3-89e1-9f8c5bf7472f
                © 2018 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
                : 12 March 2018
                : 10 April 2018
                Categories
                Review

                gut microbiome,obesity,metabolic syndrome,type 2 diabetes mellitus,type 1 diabetes mellitus,butyrate,probiotics,lipopolysaccharides,faecal microbiota transfer,metformin

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