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      Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes

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          Abstract

          The gut microbiota has been linked to the development of obesity and type 2 diabetes (T2D). The underlying mechanisms as to how intestinal microbiota may contribute to T2D are only partly understood. It becomes progressively clear that T2D is characterized by a chronic state of low-grade inflammation, which has been linked to the development of insulin resistance. Here, we review the current evidence that intestinal microbiota, and the metabolites they produce, could drive the development of insulin resistance in obesity and T2D, possibly by initiating an inflammatory response. First, we will summarize major findings about immunological and gut microbial changes in these metabolic diseases. Next, we will give a detailed view on how gut microbial changes have been implicated in low-grade inflammation. Lastly, we will critically discuss clinical studies that focus on the interaction between gut microbiota and the immune system in metabolic disease. Overall, there is strong evidence that the tripartite interaction between gut microbiota, host immune system and metabolism is a critical partaker in the pathophysiology of obesity and T2D.

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          Most cited references358

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          WITHDRAWN: Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition

          To provide global estimates of diabetes prevalence for 2019 and projections for 2030 and 2045.
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            An obesity-associated gut microbiome with increased capacity for energy harvest.

            The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
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              Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic.

              An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                16 October 2020
                2020
                : 11
                : 571731
                Affiliations
                [1] 1Department of Internal Medicine, Amsterdam University Medical Center (UMC), Vrije Universiteit (VU) University Medical Center , Amsterdam, Netherlands
                [2] 2Department of Experimental Vascular Medicine, Amsterdam University Medical Center (UMC), Academic Medical Center , Amsterdam, Netherlands
                [3] 3Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute , Vancouver, BC, Canada
                [4] 4Department of Surgery, University of British Columbia and BC Children's Hospital Research Institute , Vancouver, BC, Canada
                Author notes

                Edited by: Yang Mao-Draayer, University of Michigan, United States

                Reviewed by: Andy Wullaert, Ghent University, Belgium; Zhengxiang He, Icahn School of Medicine at Mount Sinai, United States

                *Correspondence: Torsten P. M. Scheithauer t.p.scheithauer@ 123456amsterdamumc.nl

                This article was submitted to Mucosal Immunity, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2020.571731
                7596417
                33178196
                6d80a79a-2de4-404a-b737-6b69ffccd7a8
                Copyright © 2020 Scheithauer, Rampanelli, Nieuwdorp, Vallance, Verchere, van Raalte and Herrema.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 June 2020
                : 11 September 2020
                Page count
                Figures: 6, Tables: 1, Equations: 0, References: 358, Pages: 29, Words: 24164
                Funding
                Funded by: Canadian Institutes of Health Research 10.13039/501100000024
                Funded by: Diabetes Fonds 10.13039/501100003092
                Funded by: Juvenile Diabetes Research Foundation International 10.13039/100000901
                Categories
                Immunology
                Review

                Immunology
                microbiota,obesity,metainflammation,metabolism,diabetes
                Immunology
                microbiota, obesity, metainflammation, metabolism, diabetes

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