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      Six-Week Endurance Exercise Alters Gut Metagenome That Is not Reflected in Systemic Metabolism in Over-weight Women

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          Abstract

          Recent studies suggest that exercise alters the gut microbiome. We determined whether six-weeks endurance exercise, without changing diet, affected the gut metagenome and systemic metabolites of overweight women. Previously sedentary overweight women ( n = 19) underwent a six-weeks endurance exercise intervention, but two were excluded due to antibiotic therapy. The gut microbiota composition and functions were analyzed by 16S rRNA gene amplicon sequencing and metagenomics. Body composition was analyzed with DXA X-ray densitometer and serum metabolomics with NMR metabolomics. Total energy and energy-yielding nutrient intakes were analyzed from food records using Micro-Nutrica software. Serum clinical variables were determined with KONELAB instrument. Soluble Vascular Adhesion Protein 1 (VAP-1) was measured with ELISA and its' enzymatic activity as produced hydrogen peroxide. The exercise intervention was effective, as maximal power and maximum rate of oxygen consumption increased while android fat mass decreased. No changes in diet were observed. Metagenomic analysis revealed taxonomic shifts including an increase in Akkermansia and a decrease in Proteobacteria. These changes were independent of age, weight, fat % as well as energy and fiber intake. Training slightly increased Jaccard distance of genus level β-diversity. Training did not alter the enriched metagenomic pathways, which, according to Bray Curtis dissimilarity analysis, may have been due to that only half of the subjects' microbiomes responded considerably to exercise. Nevertheless, tranining decreased the abundance of several genes including those related to fructose and amino acid metabolism. These metagenomic changes, however, were not translated into major systemic metabolic changes as only two metabolites, phospholipids and cholesterol in large VLDL particles, decreased after exercise. Training also decreased the amine oxidase activity of pro-inflammatory VAP-1, whereas no changes in CRP were detected. All clinical blood variables were within normal range, yet exercise slightly increased glucose and decreased LDL and HDL. In conclusion, exercise training modified the gut microbiome without greatly affecting systemic metabolites or body composition. Based on our data and existing literature, we propose that especially Akkermansia and Proteobacteria are exercise-responsive taxa. Our results warrant the need for further studies in larger cohorts to determine whether exercise types other than endurance exercise also modify the gut metagenome.

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          Most cited references31

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          Effects of gut microbes on nutrient absorption and energy regulation.

          Malnutrition may manifest as either obesity or undernutrition. Accumulating evidence suggests that the gut microbiota plays an important role in the harvest, storage, and expenditure of energy obtained from the diet. The composition of the gut microbiota has been shown to differ between lean and obese humans and mice; however, the specific roles that individual gut microbes play in energy harvest remain uncertain. The gut microbiota may also influence the development of conditions characterized by chronic low-level inflammation, such as obesity, through systemic exposure to bacterial lipopolysaccharide derived from the gut microbiota. In this review, the role of the gut microbiota in energy harvest and fat storage is explored, as well as differences in the microbiota in obesity and undernutrition.
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            Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children

            Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2–7 year-old Finnish children (N=142; sampled at two time points) is associated with a long-lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics.
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              Immune function in sport and exercise.

              Regular moderate exercise is associated with a reduced incidence of infection compared with a completely sedentary state. However, prolonged bouts of strenuous exercise cause a temporary depression of various aspects of immune function (e.g., neutrophil respiratory burst, lymphocyte proliferation, monocyte antigen presentation) that usually lasts approximately 3-24 h after exercise, depending on the intensity and duration of the exercise bout. Postexercise immune function dysfunction is most pronounced when the exercise is continuous, prolonged (>1.5 h), of moderate to high intensity (55-75% maximum O(2) uptake), and performed without food intake. Periods of intensified training (overreaching) lasting 1 wk or more may result in longer lasting immune dysfunction. Although elite athletes are not clinically immune deficient, it is possible that the combined effects of small changes in several immune parameters may compromise resistance to common minor illnesses, such as upper respiratory tract infection. However, this may be a small price to pay as the anti-inflammatory effects of exercise mediated through cytokines and/or downregulation of toll-like receptor expression are likely mediators of many of the long-term health benefits of regular exercise.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                03 October 2018
                2018
                : 9
                : 2323
                Affiliations
                [1] 1Institute of Biomedicine, University of Turku , Turku, Finland
                [2] 2Department of Clinical Microbiology and Immunology, Turku University Hospital , Turku, Finland
                [3] 3Faculty of Sport and Health Sciences, University of Jyväskylä , Jyväskylä, Finland
                [4] 4Department of Biology, University of Turku , Turku, Finland
                [5] 5Medicity Research Laboratory, University of Turku , Turku, Finland
                [6] 6Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku , Turku, Finland
                [7] 7Department of Health and Physical Activity, Paavo Nurmi Centre, University of Turku , Turku, Finland
                [8] 8Turku Centre for Biotechnology, University of Turku , Turku, Finland
                [9] 9Sequencing and Bioinformatics Service, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO-Salud Pública) , Valencia, Spain
                Author notes

                Edited by: Rachel Susan Poretsky, University of Illinois at Chicago, United States

                Reviewed by: Alfonso Benítez-Páez, Instituto de Agroquímica y Tecnología de Alimentos (IATA), Spain; Craig Horswill, University of Illinois at Chicago, United States

                *Correspondence: Satu Pekkala satu.p.pekkala@ 123456jyu.fi

                This article was submitted to Systems Microbiology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2018.02323
                6178902
                30337914
                e9e39c67-5f31-4956-81ad-a056b084d235
                Copyright © 2018 Munukka, Ahtiainen, Puigbó, Jalkanen, Pahkala, Keskitalo, Kujala, Pietilä, Hollmén, Elo, Huovinen, D'Auria and Pekkala.

                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
                : 27 March 2018
                : 11 September 2018
                Page count
                Figures: 6, Tables: 7, Equations: 0, References: 54, Pages: 16, Words: 11273
                Funding
                Funded by: Juho Vainion Säätiö 10.13039/501100004037
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                exercise intervention,gut microbiota composition,gut microbiota function,systemic metabolites,cardiovascular effects

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