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  • 1
    Publication Date: 2015-12-04
    Description: In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681099/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681099/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Forslund, Kristoffer -- Hildebrand, Falk -- Nielsen, Trine -- Falony, Gwen -- Le Chatelier, Emmanuelle -- Sunagawa, Shinichi -- Prifti, Edi -- Vieira-Silva, Sara -- Gudmundsdottir, Valborg -- Krogh Pedersen, Helle -- Arumugam, Manimozhiyan -- Kristiansen, Karsten -- Voigt, Anita Yvonne -- Vestergaard, Henrik -- Hercog, Rajna -- Igor Costea, Paul -- Kultima, Jens Roat -- Li, Junhua -- Jorgensen, Torben -- Levenez, Florence -- Dore, Joel -- MetaHIT consortium -- Nielsen, H Bjorn -- Brunak, Soren -- Raes, Jeroen -- Hansen, Torben -- Wang, Jun -- Ehrlich, S Dusko -- Bork, Peer -- Pedersen, Oluf -- England -- Nature. 2015 Dec 10;528(7581):262-6. doi: 10.1038/nature15766. Epub 2015 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany. ; VIB Center for the Biology of Disease, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. ; Department of Bioscience Engineering, Vrije Universiteit Brussel, 1040 Brussels, Belgium. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. ; Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. ; MICALIS, Institut National de la Recherche Agronomique, 78352 Jouy en Josas, France. ; Metagenopolis, Institut National de la Recherche Agronomique, 78352 Jouy en Josas, France. ; Institute of Cardiometabolism and Nutrition, 75013 Paris, France. ; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Kongens Lyngby, Denmark. ; Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark. ; Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany. ; Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany. ; Bejing Genomics Institute (BGI)-Shenzhen, 518083 Shenzhen, China. ; Research Centre for Prevention and Health, Capital Region of Denmark, 2600 Glostrup, Denmark. ; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, 2600 Copenhagen, Denmark. ; Faculty of Medicine, University of Aalborg, 9100 Aalborg, Denmark. ; Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. ; Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark. ; Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, 80205 Jeddah, Saudi Arabia. ; Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China. ; Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong. ; Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, King's College London, London SE1 9RT , UK. ; Max Delbruck Centre for Molecular Medicine, 13125 Berlin, Germany. ; Department of Bioinformatics, University of Wuerzburg, 97074 Wurzburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26633628" target="_blank"〉PubMed〈/a〉
    Keywords: Biodiversity ; Diabetes Mellitus, Type 2/drug therapy/*microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/genetics/*physiology ; Humans ; Hypoglycemic Agents/pharmacology/therapeutic use ; Male ; Metagenome/drug effects/physiology ; Metformin/*pharmacology/therapeutic use ; RNA, Ribosomal, 16S/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2012-12-12
    Description: Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short insertions/deletions, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536929/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536929/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schloissnig, Siegfried -- Arumugam, Manimozhiyan -- Sunagawa, Shinichi -- Mitreva, Makedonka -- Tap, Julien -- Zhu, Ana -- Waller, Alison -- Mende, Daniel R -- Kultima, Jens Roat -- Martin, John -- Kota, Karthik -- Sunyaev, Shamil R -- Weinstock, George M -- Bork, Peer -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG004968/HG/NHGRI NIH HHS/ -- U54HG003079/HG/NHGRI NIH HHS/ -- U54HG004968/HG/NHGRI NIH HHS/ -- England -- Nature. 2013 Jan 3;493(7430):45-50. doi: 10.1038/nature11711. Epub 2012 Dec 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222524" target="_blank"〉PubMed〈/a〉
    Keywords: Europe ; Feces/microbiology ; Genetic Variation/*genetics ; Genome, Bacterial/genetics ; Genotype ; Geographic Mapping ; Humans ; Intestines/*microbiology ; Metagenome/*genetics ; North America ; Polymorphism, Single Nucleotide/genetics ; Reference Standards ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-05-23
    Description: Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with 〉40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples, containing 〉35,000 species, we show vertical stratification with epipelagic community composition mostly driven by temperature rather than other environmental factors or geography. We identify ocean microbial core functionality and reveal that 〉73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sunagawa, Shinichi -- Coelho, Luis Pedro -- Chaffron, Samuel -- Kultima, Jens Roat -- Labadie, Karine -- Salazar, Guillem -- Djahanschiri, Bardya -- Zeller, Georg -- Mende, Daniel R -- Alberti, Adriana -- Cornejo-Castillo, Francisco M -- Costea, Paul I -- Cruaud, Corinne -- d'Ovidio, Francesco -- Engelen, Stefan -- Ferrera, Isabel -- Gasol, Josep M -- Guidi, Lionel -- Hildebrand, Falk -- Kokoszka, Florian -- Lepoivre, Cyrille -- Lima-Mendez, Gipsi -- Poulain, Julie -- Poulos, Bonnie T -- Royo-Llonch, Marta -- Sarmento, Hugo -- Vieira-Silva, Sara -- Dimier, Celine -- Picheral, Marc -- Searson, Sarah -- Kandels-Lewis, Stefanie -- Tara Oceans coordinators -- Bowler, Chris -- de Vargas, Colomban -- Gorsky, Gabriel -- Grimsley, Nigel -- Hingamp, Pascal -- Iudicone, Daniele -- Jaillon, Olivier -- Not, Fabrice -- Ogata, Hiroyuki -- Pesant, Stephane -- Speich, Sabrina -- Stemmann, Lars -- Sullivan, Matthew B -- Weissenbach, Jean -- Wincker, Patrick -- Karsenti, Eric -- Raes, Jeroen -- Acinas, Silvia G -- Bork, Peer -- New York, N.Y. -- Science. 2015 May 22;348(6237):1261359. doi: 10.1126/science.1261359.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium. Department of Applied Biological Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. ; CEA-Institut de Genomique, GENOSCOPE, 2 rue Gaston Cremieux, 91057 Evry, France. ; Department of Marine Biology and Oceanography, Institute of Marine Sciences (ICM)-CSIC, Pg. Maritim de la Barceloneta, 37-49, Barcelona E08003, Spain. ; Sorbonne Universites, UPMC, Universite Paris 06, CNRS-IRD-MNHN, LOCEAN Laboratory, 4 Place Jussieu, 75005 Paris France. ; CNRS, UMR 7093, Laboratoire d'Oceanographie de Villefranche-sur-Mer, Observatoire Oceanologique, F-06230 Villefranche-sur-mer, France. Sorbonne Universites, UPMC Universite Paris 06, UMR 7093, LOV, Observatoire Oceanologique, F-06230 Villefranche-sur-mer, France. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. Laboratoire de Physique des Oceans UBO-IUEM, Place Copernic 29820 Plouzane, France. ; Aix Marseille Universite CNRS IGS UMR 7256, 13288 Marseille, France. ; Department of Ecology and Evolutionary Biology, University of Arizona, 1007 East Lowell Street, Tucson, AZ 85721, USA. ; Department of Marine Biology and Oceanography, Institute of Marine Sciences (ICM)-CSIC, Pg. Maritim de la Barceloneta, 37-49, Barcelona E08003, Spain. Department of Hydrobiology, Federal University of Sao Carlos (UFSCar), Rodovia Washington Luiz, 13565-905 Sao Carlos, Sao Paulo, Brazil. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, UPMC Universite Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Directors' Research, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. ; CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, UPMC Universite Paris 06, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; CNRS UMR 7232, BIOM, Avenue du Fontaule, 66650 Banyuls-sur-Mer, France. Sorbonne Universites Paris 06, OOB UPMC, Avenue du Fontaule, 66650 Banyuls-sur-Mer, France. ; Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy. ; CEA-Institut de Genomique, GENOSCOPE, 2 rue Gaston Cremieux, 91057 Evry, France. CNRS, UMR 8030, CP5706, Evry, France. Universite d'Evry, UMR 8030, CP5706, Evry, France. ; Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto, 611-001, Japan. ; PANGAEA, Data Publisher for Earth and Environmental Science, University of Bremen, Bremen, Germany. MARUM, Center for Marine Environmental Sciences, University of Bremen, Bremen, Germany. ; Department of Geosciences, Laboratoire de Meteorologie Dynamique (LMD), Ecole Normale Superieure, 24 rue Lhomond, 75231 Paris Cedex 05, France. Laboratoire de Physique des Oceans UBO-IUEM, Place Copernic, 29820 Plouzane, France. ; Ecole Normale Superieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, F-75005 Paris, France. Directors' Research, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium. Department of Applied Biological Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Department of Marine Biology and Oceanography, Institute of Marine Sciences (ICM)-CSIC, Pg. Maritim de la Barceloneta, 37-49, Barcelona E08003, Spain. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Max-Delbruck-Centre for Molecular Medicine, 13092 Berlin, Germany. sunagawa@embl.de karsenti@embl.de jeroen.raes@vib-kuleuven.be sacinas@icm.csic.es bork@embl.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999513" target="_blank"〉PubMed〈/a〉
    Keywords: Databases, Genetic ; Ecosystem ; Gastrointestinal Tract/microbiology ; Genetic Variation ; Humans ; Metagenome ; Microbiota/*genetics ; Oceans and Seas ; Plankton/*classification/genetics/isolation & purification ; Seawater/*microbiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2016-08-11
    Description: : MOCAT2 is a software pipeline for metagenomic sequence assembly and gene prediction with novel features for taxonomic and functional abundance profiling. The automated generation and efficient annotation of non-redundant reference catalogs by propagating pre-computed assignments from 18 databases covering various functional categories allows for fast and comprehensive functional characterization of metagenomes. Availability and Implementation: MOCAT2 is implemented in Perl 5 and Python 2.7, designed for 64-bit UNIX systems and offers support for high-performance computer usage via LSF, PBS or SGE queuing systems; source code is freely available under the GPL3 license at http://mocat.embl.de . Contact : bork@embl.de Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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