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      Extensive impact of non-antibiotic drugs on human gut bacteria

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          Abstract

          A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. We screened >1000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain. Particular classes such as the chemically diverse antipsychotics were overrepresented. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies, providing in vivo relevance for our screen. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting that non-antibiotics may promote antibiotic resistance. Our results provide a comprehensive resource for future research on drug-microbiome interactions, opening new paths for side effect control and drug repurposing, and broaden our view on antibiotic resistance.

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          Most cited references37

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Bayesian estimation supersedes the t test.

            Bayesian estimation for 2 groups provides complete distributions of credible values for the effect size, group means and their difference, standard deviations and their difference, and the normality of the data. The method handles outliers. The decision rule can accept the null value (unlike traditional t tests) when certainty in the estimate is high (unlike Bayesian model comparison using Bayes factors). The method also yields precise estimates of statistical power for various research goals. The software and programs are free and run on Macintosh, Windows, and Linux platforms. PsycINFO Database Record (c) 2013 APA, all rights reserved.
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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
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                15 August 2018
                19 March 2018
                29 March 2018
                19 September 2018
                : 555
                : 7698
                : 623-628
                Affiliations
                [1 ]European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany
                [2 ]European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany
                [3 ]Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan
                [4 ]Max-Delbrück-Centre for Molecular Medicine, Berlin, Germany
                [5 ]Molecular Medicine Partnership Unit, Heidelberg, Germany
                [6 ]Department of Bioinformatics, Biocenter, University of Würzburg, Germany
                Author notes
                [* ]Correspondence and requests for materials should be addressed: zeller@ 123456embl.de , patil@ 123456embl.de , bork@ 123456embl.de & typas@ 123456embl.de
                [7]

                Current address: Institute for Biology, Humboldt University Berlin, Germany

                Article
                EMS76168
                10.1038/nature25979
                6108420
                29555994
                2888e071-e50c-422e-9dc1-019b6a0bab89

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

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