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      Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

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          Abstract

          Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

          Abstract

          The potential recovery of the human gut microbiota after an antibiotic treatment, and its effects on our health, are poorly understood. Here, the authors use a mouse model mimicking paediatric antibiotic use to shed new light into these processes.

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          Most cited references35

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          Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship.

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            Antibiotic growth promoters in agriculture: history and mode of action

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              Nonalcoholic fatty liver disease: pathology and pathogenesis.

              Nonalcoholic fatty liver disease (NAFLD) is recognized as the leading cause of chronic liver disease in adults and children. NAFLD encompasses a spectrum of liver injuries ranging from steatosis to steatohepatitis with or without fibrosis. Fibrosis may progress to cirrhosis and complications including hepatocellular carcinoma. Histologic findings represent the complexity of pathophysiology. NAFLD is closely associated with obesity and is most closely linked with insulin resistance; the current Western diet, high in saturated fats and fructose, plays a significant role. There are several mechanisms by which excess triglycerides are acquired and accumulate in hepatocytes. Formation of steatotic droplets may be disordered in NAFLD. Visceral adipose tissue dysfunction in obesity and insulin resistance results in aberrant cytokine expression; many cytokines have a role in liver injury in NAFLD. Cellular stress and immune reactions, as well as the endocannabinoid system, have been implicated in animal models and in some human studies.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Pub. Group
                2041-1723
                30 June 2015
                2015
                : 6
                : 7486
                Affiliations
                [1 ]Department of Medicine, New York University School of Medicine , New York, New York 10016, USA
                [2 ]Department of Microbiology, New York University School of Medicine , New York, New York 10016, USA
                [3 ]New York Harbor Department of Veterans Affairs Medical Center , New York, New York 10010, USA
                [4 ]The Genome Institute at Washington University , St. Louis, Missouri 63108, USA
                [5 ]Department of Pediatrics, Washington University School of Medicine , St. Louis, Missouri, USA, 63110
                [6 ]Division of Biostatistics, Department of Population Health, NYU Langone Medical Center , New York, New York 10016, USA
                [7 ]Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine , St. Louis, Missouri 63110, USA
                [8 ]Center for Health Informatics and Bioinformatics, New York University School of Medicine , New York, New York 10016, USA
                [9 ]The Jackson Laboratory for Genomic Medicine , Farmington, Connecticut 06117, USA
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                ncomms8486
                10.1038/ncomms8486
                4491183
                26123276
                2e13aa6c-87f1-4553-81d9-aed09d99be2c
                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
                : 25 February 2015
                : 13 May 2015
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