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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: 2013-08-30
    Description: We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Le Chatelier, Emmanuelle -- Nielsen, Trine -- Qin, Junjie -- Prifti, Edi -- Hildebrand, Falk -- Falony, Gwen -- Almeida, Mathieu -- Arumugam, Manimozhiyan -- Batto, Jean-Michel -- Kennedy, Sean -- Leonard, Pierre -- Li, Junhua -- Burgdorf, Kristoffer -- Grarup, Niels -- Jorgensen, Torben -- Brandslund, Ivan -- Nielsen, Henrik Bjorn -- Juncker, Agnieszka S -- Bertalan, Marcelo -- Levenez, Florence -- Pons, Nicolas -- Rasmussen, Simon -- Sunagawa, Shinichi -- Tap, Julien -- Tims, Sebastian -- Zoetendal, Erwin G -- Brunak, Soren -- Clement, Karine -- Dore, Joel -- Kleerebezem, Michiel -- Kristiansen, Karsten -- Renault, Pierre -- Sicheritz-Ponten, Thomas -- de Vos, Willem M -- Zucker, Jean-Daniel -- Raes, Jeroen -- Hansen, Torben -- MetaHIT consortium -- Bork, Peer -- Wang, Jun -- Ehrlich, S Dusko -- Pedersen, Oluf -- England -- Nature. 2013 Aug 29;500(7464):541-6. doi: 10.1038/nature12506.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INRA, Institut National de la Recherche Agronomique, US1367 Metagenopolis, 78350 Jouy en Josas, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23985870" target="_blank"〉PubMed〈/a〉
    Keywords: Adiposity ; Adult ; Bacteria/classification/genetics/*isolation & purification ; Biomarkers/*metabolism ; Body Mass Index ; Case-Control Studies ; Diet ; Dyslipidemias/microbiology ; Energy Metabolism ; Europe/ethnology ; European Continental Ancestry Group ; Female ; Gastrointestinal Tract/*microbiology ; Genes, Bacterial ; Humans ; Inflammation/microbiology ; Insulin Resistance ; Male ; *Metagenome/genetics ; Obesity/metabolism/microbiology ; Overweight/metabolism/microbiology ; Phylogeny ; Thinness/microbiology ; Weight Gain ; Weight Loss
    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: 2015-09-19
    Description: The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes for signatures of adaptation revealed signals at several loci, with the strongest signal located in a cluster of fatty acid desaturases that determine PUFA levels. The selected alleles are associated with multiple metabolic and anthropometric phenotypes and have large effect sizes for weight and height, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fumagalli, Matteo -- Moltke, Ida -- Grarup, Niels -- Racimo, Fernando -- Bjerregaard, Peter -- Jorgensen, Marit E -- Korneliussen, Thorfinn S -- Gerbault, Pascale -- Skotte, Line -- Linneberg, Allan -- Christensen, Cramer -- Brandslund, Ivan -- Jorgensen, Torben -- Huerta-Sanchez, Emilia -- Schmidt, Erik B -- Pedersen, Oluf -- Hansen, Torben -- Albrechtsen, Anders -- Nielsen, Rasmus -- R01-HG003229/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1343-7. doi: 10.1126/science.aab2319.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK. Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA. ; The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. ; Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA. ; National Institute of Public Health, University of Southern Denmark, 1353 Copenhagen, Denmark. Greenland Center for Health Research, University of Greenland, Nuuk, Greenland. ; National Institute of Public Health, University of Southern Denmark, 1353 Copenhagen, Denmark. Steno Diabetes Center, 2820 Gentofte, Denmark. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark. ; Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK. Department of Anthropology, University College London, London WC1H 0BW, UK. ; Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark. Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ; Department of Medicine, Lillebaelt Hospital, Vejle, Denmark. ; Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark. ; Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Faculty of Medicine, University of Aalborg, Aalborg, Denmark. ; School of Natural Sciences, University of California-Merced, Merced, CA 95343, USA. ; Faculty of Medicine, University of Aalborg, Aalborg, Denmark. Department of Cardiology, Aalborg University Hospital, 9100 Aalborg, Denmark. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu. ; The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu. ; Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA. Department of Statistics, University of California-Berkeley, Berkeley, CA 94720, USA. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383953" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization/*genetics ; Alleles ; Arctic Regions ; Body Height/genetics ; Body Weight/genetics ; Chromosomes, Human, Pair 11/genetics ; Climate ; *Diet, High-Fat ; Fatty Acids, Omega-3/*administration & dosage/analysis ; Female ; Genetic Loci ; Genome, Human/genetics ; Genome-Wide Association Study ; Greenland ; Humans ; Inuits/*genetics ; Linkage Disequilibrium ; Male ; Membrane Lipids/analysis/genetics ; Polymorphism, Single Nucleotide ; Selection, Genetic
    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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