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      Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation

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          Abstract

          The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed.

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          Most cited references114

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          Bile acids: regulation of synthesis.

          Bile acids are physiological detergents that generate bile flow and facilitate intestinal absorption and transport of lipids, nutrients, and vitamins. Bile acids also are signaling molecules and inflammatory agents that rapidly activate nuclear receptors and cell signaling pathways that regulate lipid, glucose, and energy metabolism. The enterohepatic circulation of bile acids exerts important physiological functions not only in feedback inhibition of bile acid synthesis but also in control of whole-body lipid homeostasis. In the liver, bile acids activate a nuclear receptor, farnesoid X receptor (FXR), that induces an atypical nuclear receptor small heterodimer partner, which subsequently inhibits nuclear receptors, liver-related homolog-1, and hepatocyte nuclear factor 4alpha and results in inhibiting transcription of the critical regulatory gene in bile acid synthesis, cholesterol 7alpha-hydroxylase (CYP7A1). In the intestine, FXR induces an intestinal hormone, fibroblast growth factor 15 (FGF15; or FGF19 in human), which activates hepatic FGF receptor 4 (FGFR4) signaling to inhibit bile acid synthesis. However, the mechanism by which FXR/FGF19/FGFR4 signaling inhibits CYP7A1 remains unknown. Bile acids are able to induce FGF19 in human hepatocytes, and the FGF19 autocrine pathway may exist in the human livers. Bile acids and bile acid receptors are therapeutic targets for development of drugs for treatment of cholestatic liver diseases, fatty liver diseases, diabetes, obesity, and metabolic syndrome.
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            Gut microbial metabolites in obesity, NAFLD and T2DM

            Evidence is accumulating that the gut microbiome is involved in the aetiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fibre), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fibre, the major energy source for the microbiota, is limited here. This proteolytic fermentation yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermentation could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved.
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              Responses of Gut Microbiota and Glucose and Lipid Metabolism to Prebiotics in Genetic Obese and Diet-Induced Leptin-Resistant Mice

              OBJECTIVE To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice. RESEARCH DESIGN AND METHODS Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models. RESULTS In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat–fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters. CONCLUSIONS We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.
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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                16 October 2019
                October 2019
                : 7
                : 10
                : 456
                Affiliations
                [1 ]Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea; bkannanbio@ 123456gmail.com (K.B.); ramachandran865@ 123456gmail.com (R.C.); rubab.momna@ 123456gmail.com (M.R.); ericdaliri@ 123456yahoo.com (E.B.-M.D.); elahidr@ 123456gmail.com (F.E.)
                [2 ]Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon, Gangwon-do 24341, Korea; donghwan@ 123456kangwon.ac.kr
                [3 ]Department of Plant Biology and Biotechnology, Loyola College, Chennai 600-034, India; agastian@ 123456loyolacollege.edu
                [4 ]Three & Four Co., Ltd., 992-15, Jusan-ri, Hojeo-myeon, Wonju-si 26460, Korea; 3n4world@ 123456hanmail.net
                Author notes
                [* ]Correspondence: deoghwa@ 123456kangwon.ac.kr ; Tel./Fax: +82-33-250-6457
                Author information
                https://orcid.org/0000-0003-2316-5249
                https://orcid.org/0000-0001-8831-7632
                https://orcid.org/0000-0003-4250-2335
                Article
                microorganisms-07-00456
                10.3390/microorganisms7100456
                6843309
                31623075
                db136e2b-87b0-4e9e-8b8e-8683888afad2
                © 2019 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
                : 26 July 2019
                : 12 October 2019
                Categories
                Review

                obesity,gut microbiome,probiotics,mechanism,diet
                obesity, gut microbiome, probiotics, mechanism, diet

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