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      Toward a Predictive Understanding of Earth’s Microbiomes to Address 21st Century Challenges

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          ABSTRACT

          Microorganisms have shaped our planet and its inhabitants for over 3.5 billion years. Humankind has had a profound influence on the biosphere, manifested as global climate and land use changes, and extensive urbanization in response to a growing population. The challenges we face to supply food, energy, and clean water while maintaining and improving the health of our population and ecosystems are significant. Given the extensive influence of microorganisms across our biosphere, we propose that a coordinated, cross-disciplinary effort is required to understand, predict, and harness microbiome function. From the parallelization of gene function testing to precision manipulation of genes, communities, and model ecosystems and development of novel analytical and simulation approaches, we outline strategies to move microbiome research into an era of causality. These efforts will improve prediction of ecosystem response and enable the development of new, responsible, microbiome-based solutions to significant challenges of our time.

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          Most cited references112

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          Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.

          In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Multiorganismal insects: diversity and function of resident microorganisms.

            All insects are colonized by microorganisms on the insect exoskeleton, in the gut and hemocoel, and within insect cells. The insect microbiota is generally different from microorganisms in the external environment, including ingested food. Specifically, certain microbial taxa are favored by the conditions and resources in the insect habitat, by their tolerance of insect immunity, and by specific mechanisms for their transmission. The resident microorganisms can promote insect fitness by contributing to nutrition, especially by providing essential amino acids, B vitamins, and, for fungal partners, sterols. Some microorganisms protect their insect hosts against pathogens, parasitoids, and other parasites by synthesizing specific toxins or modifying the insect immune system. Priorities for future research include elucidation of microbial contributions to detoxification, especially of plant allelochemicals in phytophagous insects, and resistance to pathogens; as well as their role in among-insect communication; and the potential value of manipulation of the microbiota to control insect pests.
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              Tn-seq; high-throughput parallel sequencing for fitness and genetic interaction studies in microorganisms

              Biological pathways are structured in complex networks of interacting genes. Solving the architecture of such networks may provide valuable information, such as how microorganisms cause disease. Here we present a method (Tn-seq) for accurately determining quantitative genetic interactions on a genome-wide scale in microorganisms. Tn-seq is based on the assembly of a saturated Mariner transposon insertion library. After library selection, changes in frequency of each insertion mutant are determined by sequencing of the flanking regions en masse. These changes are used to calculate each mutant’s fitness. Fitness was determined for each gene of the gram-positive bacterium Streptococcus pneumoniae, a causative agent of pneumonia and meningitis. A genome-wide screen for genetic interactions identified both alleviating and aggravating interactions that could be further divided into seven distinct categories. Due to the wide activity of the Mariner transposon, Tn-seq has the potential to contribute to the exploration of complex pathways across many different species.
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                Author and article information

                Contributors
                Role: Editor, mBio
                Role: Senior Editor, mSystems
                Role: Senior Editor, mSystems
                Role: Editor, mSystems
                Journal
                mBio
                MBio
                mbio
                mbio
                mBio
                mBio
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2150-7511
                13 May 2016
                May-Jun 2016
                : 7
                : 3
                : e00714-16
                Affiliations
                [a ]Departments of Microbiology and Medicine, New York University School of Medicine, New York, New York, USA
                [b ]The Ecosystems Center, Marine Biological Laboratory, Woods Hole, Massachusetts, USA
                [c ]Stanford Center for Biomedical Ethics, Stanford University, Palo Alto, California, USA
                [d ]Department of Biology and Howard Hughes Medical Institute, University of North Carolina, Chapel Hill, North Carolina, USA
                [e ]Department of Bacteriology, Great Lakes Bioenergy Research Center and Wisconsin Energy Institute, University of Wisconsin—Madison, Madison, Wisconsin, USA
                [f ]Biology and the Built Environment Center, University of Oregon, Eugene, Oregon, USA
                [g ]Department of Biology, Institute of Ecology and Evolution, University of Oregon, Eugene, Oregon, USA
                [h ]Departments of Pediatrics and Computer Science & Engineering, and Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
                [i ]Biosciences, Lawrence Berkeley National Laboratory, Berkeley, California, USA
                [j ]Division of Biostatistics, Gladstone Institutes and Institute for Human Genetics, Institute for Computational Health Science, University of California, San Francisco, California, USA
                [k ]Earth and Environmental Sciences, Lawrence Berkeley National Lab, Berkeley, California, USA
                [l ]Department of Environmental Science, Policy and Management, University of California, Berkeley, California, USA
                Author notes
                Address correspondence to Eoin L. Brodie, ELBrodie@ 123456lbl.gov .
                Author information
                http://orcid.org/0000-0001-8738-2467
                http://orcid.org/0000-0002-8453-8435
                Article
                mBio00714-16
                10.1128/mBio.00714-16
                4895116
                27178263
                08ce9379-cbda-459a-8517-98189114ded4
                Copyright © 2016 Blaser et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 184, Pages: 16, Words: 13798
                Funding
                E.L.B. is supported by the Genomes-to-Watersheds Subsurface Biogeochemical Research Scientific Focus Area, and T.R.N. is supported by ENIGMA-Ecosystems and Networks Integrated with Genes and Molecular Assemblies ( http://enigma.lbl.gov) Scientific Focus Area, funded by the U.S. Department of Energy (US DOE), Office of Science, Office of Biological and Environmental Research under contract no. DE-AC02-05CH11231 to Lawrence Berkeley National Laboratory (LBNL). M.E.M. is also supported by the US DOE, Office of Science, Office of Biological and Environmental Research under contract no. DE-AC02-05CH11231. Z.G.C. is supported by National Science Foundation Integrative Organismal Systems grant #1355085, and by US DOE, Office of Biological and Environmental Research grant # DE-SC0008182 ER65389 from the Terrestrial Ecosystem Science Program. M.J.B. is supported by R01 DK 090989 from the NIH. T.J.D. is supported by the US DOE Office of Science’s Great Lakes Bioenergy Research Center, grant DE-FC02-07ER64494. J.L.G. is supported by Alfred P. Sloan Foundation G 2-15-14023. R.K. is supported by grants from the NSF (DBI-1565057) and NIH (U01AI24316, U19AI113048, P01DK078669, 1U54DE023789, U01HG006537). K.S.P. is supported by grants from the NSF DMS-1069303 and the Gordon & Betty Moore Foundation (#3300).
                Categories
                Editorial
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                May/June 2016

                Life sciences
                Life sciences

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