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      Exercise Prevents Weight Gain and Alters the Gut Microbiota in a Mouse Model of High Fat Diet-Induced Obesity

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          Abstract

          Background

          Diet-induced obesity (DIO) is a significant health concern which has been linked to structural and functional changes in the gut microbiota. Exercise (Ex) is effective in preventing obesity, but whether Ex alters the gut microbiota during development with high fat (HF) feeding is unknown.

          Objective

          Determine the effects of voluntary Ex on the gastrointestinal microbiota in LF-fed mice and in HF-DIO.

          Methods

          Male C57BL/6 littermates (5 weeks) were distributed equally into 4 groups: low fat (LF) sedentary (Sed) LF/Sed, LF/Ex, HF/Sed and HF/Ex. Mice were individually housed and LF/Ex and HF/Ex cages were equipped with a wheel and odometer to record Ex. Fecal samples were collected at baseline, 6 weeks and 12 weeks and used for bacterial DNA isolation. DNA was subjected both to quantitative PCR using primers specific to the 16S rRNA encoding genes for Bacteroidetes and Firmicutes and to sequencing for lower taxonomic identification using the Illumina MiSeq platform. Data were analyzed using a one or two-way ANOVA or Pearson correlation.

          Results

          HF diet resulted in significantly greater body weight and adiposity as well as decreased glucose tolerance that were prevented by voluntary Ex (p<0.05). Visualization of Unifrac distance data with principal coordinates analysis indicated clustering by both diet and Ex at week 12. Sequencing demonstrated Ex-induced changes in the percentage of major bacterial phyla at 12 weeks. A correlation between total Ex distance and the ΔCt Bacteroidetes: ΔCt Firmicutes ratio from qPCR demonstrated a significant inverse correlation (r 2 = 0.35, p = 0.043).

          Conclusion

          Ex induces a unique shift in the gut microbiota that is different from dietary effects. Microbiota changes may play a role in Ex prevention of HF-DIO.

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          Most cited references71

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          QIIME allows analysis of high-throughput community sequencing data.

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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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              Greengenes, a Chimera-Checked 16S rRNA Gene Database and Workbench Compatible with ARB

              A 16S rRNA gene database ( http://greengenes.lbl.gov ) addresses limitations of public repositories by providing chimera screening, standard alignment, and taxonomic classification using multiple published taxonomies. It was found that there is incongruent taxonomic nomenclature among curators even at the phylum level. Putative chimeras were identified in 3% of environmental sequences and in 0.2% of records derived from isolates. Environmental sequences were classified into 100 phylum-level lineages in the Archaea and Bacteria .
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                26 March 2014
                : 9
                : 3
                : e92193
                Affiliations
                [1 ]Department of Physical Therapy, College of Health Sciences, Midwestern University, Downers Grove, Illinois, United States of America
                [2 ]Department of Physiology, College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois, United States of America
                [3 ]Department of Biomedical Sciences, College of Health Sciences, Midwestern University, Downers Grove, Illinois, United States of America
                [4 ]College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois, United States of America
                [5 ]Department of Dental Medicine, College of Dental Medicine, Midwestern University, Downers Grove, Illinois, United States of America
                [6 ]Department of Medicine, University of Chicago, Chicago, Illinois, United States of America
                [7 ]Institute for Genomics and Systems Biology, Argonne National Laboratory, Argonne, Illinois, United States of America
                University of Tor Vergata, Italy
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CCE MJC. Performed the experiments: JWK MCS JD LM CCE MJC YW SL VL EBC DAA DS AG. Analyzed the data: CCE KJL JWK JD. Contributed reagents/materials/analysis tools: MJC KJL JWK JD. Wrote the paper: CCE KJL MJC.

                Article
                PONE-D-13-39146
                10.1371/journal.pone.0092193
                3966766
                24670791
                1d804a89-aa21-448b-815b-ae94157e8c61
                Copyright @ 2014

                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 20 September 2013
                : 20 February 2014
                Page count
                Pages: 14
                Funding
                Funding was through: Midwestern University (MJC), Midwestern University College of Health Sciences Research Facilitation grants (CCE and MJC), a Kenneth A. Suarez Summer Research Fellowship (SL), National Institutes of Health (NIH) grant P30 DK 42086 to the Host-Microbe Core of the Digestive Disease Research Core Center, University of Chicago and NIH grant DK097268 (EBC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Energy Metabolism
                Computational Biology
                Genetics
                Genomics
                Metagenomics
                Microbiology
                Nutrition
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Physiological Processes
                Systems Biology
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Metabolic Disorders
                Public and Occupational Health
                Behavioral and Social Aspects of Health
                Preventive Medicine
                Sports and Exercise Medicine

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                Uncategorized

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