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  • 1
    Publication Date: 2008-12-02
    Description: The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677729/" 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/PMC2677729/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Turnbaugh, Peter J -- Hamady, Micah -- Yatsunenko, Tanya -- Cantarel, Brandi L -- Duncan, Alexis -- Ley, Ruth E -- Sogin, Mitchell L -- Jones, William J -- Roe, Bruce A -- Affourtit, Jason P -- Egholm, Michael -- Henrissat, Bernard -- Heath, Andrew C -- Knight, Rob -- Gordon, Jeffrey I -- AA09022/AA/NIAAA NIH HHS/ -- DK78669/DK/NIDDK NIH HHS/ -- ES012742/ES/NIEHS NIH HHS/ -- HD049024/HD/NICHD NIH HHS/ -- P01 DK078669/DK/NIDDK NIH HHS/ -- P01 DK078669-01/DK/NIDDK NIH HHS/ -- P30 DK056341/DK/NIDDK NIH HHS/ -- P30 DK056341-07/DK/NIDDK NIH HHS/ -- P30 DK056341-08/DK/NIDDK NIH HHS/ -- P50 ES012742/ES/NIEHS NIH HHS/ -- P50 ES012742-049001/ES/NIEHS NIH HHS/ -- R01 AA009022/AA/NIAAA NIH HHS/ -- R01 AA009022-10/AA/NIAAA NIH HHS/ -- R01 HD049024/HD/NICHD NIH HHS/ -- R01 HD049024-01/HD/NICHD NIH HHS/ -- T32 GM065103/GM/NIGMS NIH HHS/ -- T32 GM065103-07/GM/NIGMS NIH HHS/ -- UL1 TR000448/TR/NCATS NIH HHS/ -- England -- Nature. 2009 Jan 22;457(7228):480-4. doi: 10.1038/nature07540. Epub 2008 Nov 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genome Sciences, Washington University School of Medicine, St Louis, Missouri 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19043404" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Africa/ethnology ; Biodiversity ; Environment ; Europe/ethnology ; Feces/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Genotype ; Humans ; Metagenome/genetics/*physiology ; Missouri ; Molecular Sequence Data ; Mothers ; Obesity/*microbiology ; RNA, Ribosomal, 16S/analysis/genetics ; Thinness/*microbiology ; Twins, Dizygotic ; Twins, Monozygotic
    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: 2013-02-01
    Description: Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667500/" 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/PMC3667500/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Michelle I -- Yatsunenko, Tanya -- Manary, Mark J -- Trehan, Indi -- Mkakosya, Rajhab -- Cheng, Jiye -- Kau, Andrew L -- Rich, Stephen S -- Concannon, Patrick -- Mychaleckyj, Josyf C -- Liu, Jie -- Houpt, Eric -- Li, Jia V -- Holmes, Elaine -- Nicholson, Jeremy -- Knights, Dan -- Ursell, Luke K -- Knight, Rob -- Gordon, Jeffrey I -- DK078669/DK/NIDDK NIH HHS/ -- DK30292/DK/NIDDK NIH HHS/ -- F32 DK091044/DK/NIDDK NIH HHS/ -- P01 DK078669/DK/NIDDK NIH HHS/ -- P30 DK056341/DK/NIDDK NIH HHS/ -- R37 DK030292/DK/NIDDK NIH HHS/ -- T32 HD049338/HD/NICHD NIH HHS/ -- T32-HD049338/HD/NICHD NIH HHS/ -- T35 DK074375/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 1;339(6119):548-54. doi: 10.1126/science.1229000. Epub 2013 Jan 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23363771" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/metabolism ; Animals ; Arachis ; Carbohydrate Metabolism ; Child, Preschool ; Diseases in Twins/*microbiology ; Feces/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Germ-Free Life ; Humans ; Infant ; Kwashiorkor/diet therapy/epidemiology/*microbiology ; Longitudinal Studies ; Malawi/epidemiology ; Male ; *Metagenome ; Mice ; Mice, Inbred C57BL
    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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  • 3
    Publication Date: 2012-06-16
    Description: Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376388/" 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/PMC3376388/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yatsunenko, Tanya -- Rey, Federico E -- Manary, Mark J -- Trehan, Indi -- Dominguez-Bello, Maria Gloria -- Contreras, Monica -- Magris, Magda -- Hidalgo, Glida -- Baldassano, Robert N -- Anokhin, Andrey P -- Heath, Andrew C -- Warner, Barbara -- Reeder, Jens -- Kuczynski, Justin -- Caporaso, J Gregory -- Lozupone, Catherine A -- Lauber, Christian -- Clemente, Jose Carlos -- Knights, Dan -- Knight, Rob -- Gordon, Jeffrey I -- DK078669/DK/NIDDK NIH HHS/ -- K01 DK090285/DK/NIDDK NIH HHS/ -- K05 AA017688/AA/NIAAA NIH HHS/ -- P01 DK078669/DK/NIDDK NIH HHS/ -- P01 DK078669-05/DK/NIDDK NIH HHS/ -- T32 HD049338-06/HD/NICHD NIH HHS/ -- T32-HD049338/HD/NICHD NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 May 9;486(7402):222-7. doi: 10.1038/nature11053.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, Missouri 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22699611" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Age Factors ; Aged ; Bacteria/*classification/*genetics ; *Biodiversity ; Child ; Child, Preschool ; Feces/microbiology ; Female ; Geography ; Humans ; Infant ; Intestines/*microbiology ; Malawi ; Male ; *Metagenome ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Twins, Dizygotic ; Twins, Monozygotic ; United States ; Venezuela ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-06-05
    Description: Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a 'relative microbiota maturity index' and 'microbiota-for-age Z-score' that compare postnatal assembly (defined here as maturation) of a child's faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189846/" 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/PMC4189846/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Subramanian, Sathish -- Huq, Sayeeda -- Yatsunenko, Tanya -- Haque, Rashidul -- Mahfuz, Mustafa -- Alam, Mohammed A -- Benezra, Amber -- DeStefano, Joseph -- Meier, Martin F -- Muegge, Brian D -- Barratt, Michael J -- VanArendonk, Laura G -- Zhang, Qunyuan -- Province, Michael A -- Petri, William A Jr -- Ahmed, Tahmeed -- Gordon, Jeffrey I -- AI043596/AI/NIAID NIH HHS/ -- R01 AI043596/AI/NIAID NIH HHS/ -- T32 GM007067/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jun 19;510(7505):417-21. doi: 10.1038/nature13421. Epub 2014 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, Missouri 63108, USA. ; Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research, Dhaka 1212, Bangladesh. ; 1] Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, Missouri 63108, USA [2] Department of Anthropology, New School for Social Research, New York, New York 10003, USA. ; Division of Statistical Genomics, Washington University in St. Louis, St. Louis, Missouri 63108, USA. ; Departments of Medicine, Microbiology and Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896187" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/classification/genetics ; *Bacterial Physiological Phenomena ; Bangladesh ; *Biodiversity ; Feces/microbiology ; Female ; Gastrointestinal Tract/microbiology ; Humans ; Infant ; Infant Nutrition Disorders/diet therapy/*microbiology ; Male ; *Microbiota ; Models, Biological ; Nutritional Status ; 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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  • 5
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