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      Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota

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          Abstract

          Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis—as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels—but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further show that high molecular weight polysaccharides (>300 kDa) isolated from the WEGL extract produce similar anti-obesity and microbiota-modulating effects. Our results indicate that G. lucidum and its high molecular weight polysaccharides may be used as prebiotic agents to prevent gut dysbiosis and obesity-related metabolic disorders in obese individuals.

          Abstract

          Ganoderma lucidum is a medicinal mushroom used in Traditional Chinese Medicine with putative anti-diabetic properties. Here, the authors show that polysaccharides from a water extract of this mushroom exert beneficial metabolic effects by modulating the composition of the gut microbiota in mice.

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          Most cited references33

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          How glycan metabolism shapes the human gut microbiota.

          Symbiotic microorganisms that reside in the human intestine are adept at foraging glycans and polysaccharides, including those in dietary plants (starch, hemicellulose and pectin), animal-derived cartilage and tissue (glycosaminoglycans and N-linked glycans), and host mucus (O-linked glycans). Fluctuations in the abundance of dietary and endogenous glycans, combined with the immense chemical variation among these molecules, create a dynamic and heterogeneous environment in which gut microorganisms proliferate. In this Review, we describe how glycans shape the composition of the gut microbiota over various periods of time, the mechanisms by which individual microorganisms degrade these glycans, and potential opportunities to intentionally influence this ecosystem for better health and nutrition.
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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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              Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice.

              The proportion of the human gut bacterial community that is recalcitrant to culture remains poorly defined. In this report, we combine high-throughput anaerobic culturing techniques with gnotobiotic animal husbandry and metagenomics to show that the human fecal microbiota consists largely of taxa and predicted functions that are represented in its readily cultured members. When transplanted into gnotobiotic mice, complete and cultured communities exhibit similar colonization dynamics, biogeographical distribution, and responses to dietary perturbations. Moreover, gnotobiotic mice can be used to shape these personalized culture collections to enrich for taxa suited to specific diets. We also demonstrate that thousands of isolates from a single donor can be clonally archived and taxonomically mapped in multiwell format to create personalized microbiota collections. Retrieving components of a microbiota that have coexisted in single donors who have physiologic or disease phenotypes of interest and reuniting them in various combinations in gnotobiotic mice should facilitate preclinical studies designed to determine the degree to which tractable bacterial taxa are able to transmit donor traits or influence host biology.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Pub. Group
                2041-1723
                23 June 2015
                2015
                : 6
                : 7489
                Affiliations
                [1 ]Center for Molecular and Clinical Immunology, Chang Gung University , Gueishan, Taoyuan 33302, Taiwan, ROC
                [2 ]Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University , Gueishan, Taoyuan 33302, Taiwan, ROC
                [3 ]Department of Laboratory Medicine, Chang Gung Memorial Hospital, Linkou , Gueishan, Taoyuan 33305, Taiwan, ROC
                [4 ]Department of Microbiology and Immunology, Chang Gung University , Gueishan, Taoyuan 33302, Taiwan, ROC
                [5 ]Research Center of Bacterial Pathogenesis, Chang Gung University , Gueishan, Taoyuan 33302, Taiwan, ROC
                [6 ]Department of Respiratory Therapy, Fu Jen Catholic University , Xinzhuang, New Taipei City 24205, Taiwan, ROC
                [7 ]Chang Gung Biotechnology Corporation , Taipei 10508, Taiwan, ROC
                [8 ]Biochemical Engineering Research Center, Ming Chi University of Technology , Taishan, New Taipei City 24301, Taiwan, ROC
                [9 ]Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry , San Francisco, California 94103, USA
                [10 ]Laboratory of Cellular Physiology and Immunology, Rockefeller University , New York, New York 10021, USA
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                ncomms8489
                10.1038/ncomms8489
                4557287
                26102296
                b9bbc284-faa2-485f-af20-ade2a7955547
                Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 16 December 2014
                : 14 May 2015
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